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FDA Approves First Drug for MASH
, along with diet and exercise.
Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.
The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses.
The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.)
The results were published online February 6 in The New England Journal of Medicine.
“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release.
“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.
Addressing an Unmet Need
MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication.
In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo.
Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.
Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo.
The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo.
Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo.
The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.
Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.
Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.
A version of this article appeared on Medscape.com.
, along with diet and exercise.
Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.
The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses.
The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.)
The results were published online February 6 in The New England Journal of Medicine.
“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release.
“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.
Addressing an Unmet Need
MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication.
In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo.
Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.
Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo.
The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo.
Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo.
The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.
Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.
Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.
A version of this article appeared on Medscape.com.
, along with diet and exercise.
Resmetirom is a once-daily, oral thyroid hormone receptor beta-selective agonist. The FDA granted the drug breakthrough therapy designation and priority review.
The approval is based on the phase 3 MAESTRO-NASH trial, in which resmetirom was superior to placebo at achieving resolution of nonalcoholic steatohepatitis (NASH) and improving liver fibrosis in both 80-mg and 100-mg doses.
The trial used the earlier nomenclature of NASH and nonalcoholic fatty liver disease (NAFLD). An international consensus group has since changed these terms to MASH and metabolic dysfunction–associated steatotic liver disease (MASLD), respectively. (Note that the terms NASH and NAFLD will be used to discuss the trial results in this article to align with the trial’s original language.)
The results were published online February 6 in The New England Journal of Medicine.
“The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition,” lead MAESTRO-NASH investigator Stephen Harrison, MD, gastroenterologist, hepatologist, and chairman of Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, said in a news release.
“Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis. Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality,” Dr. Harrison added.
Addressing an Unmet Need
MASH is a progressive liver disease and the leading cause of liver-related mortality. The disease affects an estimated 1.5 million adults in the United States, of which, roughly 525,000 have MASH with significant fibrosis. Until now, there was no FDA-approved medication.
In the ongoing MAESTRO-NASH, 996 adults with biopsy-confirmed NASH and significant stage 2-3 fibrosis were randomly assigned to receive oral once-daily resmetirom (80 mg or 100 mg) or placebo.
Patients were followed for 52 weeks, at which point, they were assessed for the dual primary endpoints of NASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score.
Patients receiving resmetirom had a significant improvement across both doses and both primary endpoints.
At 52 weeks, NASH resolution with no worsening of fibrosis was achieved in 25.9% and 29.9% of the patients in the 80-mg and 100-mg groups, respectively, compared with 9.7% on placebo.
Fibrosis improved by at least one stage with no worsening of the NAFLD activity score in 24.2% and 25.9% of patients in the 80-mg and 100-mg groups, respectively, compared with 14.2% on placebo.
The trial also met multiple secondary endpoints, including statistically significant reduction from baseline in liver enzymes (alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase) and low-density lipoprotein cholesterol with resmetirom compared with placebo.
Improvement in fibrosis biomarkers and relevant imaging tests were also observed in resmetirom treatment groups compared with placebo.
The most common adverse events included diarrhea and nausea, which typically began early in treatment and were mild to moderate in severity. Pruritus, abdominal pain, vomiting, constipation, and dizziness were also reported.
Resmetirom is expected to be available to patients in the United States in April and will be distributed through a limited specialty pharmacy network.
Full prescribing information is available online. Prescribing information does not include a liver biopsy requirement for diagnosis.
A version of this article appeared on Medscape.com.
FDA Approves New Esophageal Cancer Drug
The US Food and Drug Administration (FDA) has approved tislelizumab-jsgr (Tevimbra, BeiGene Ltd.) as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Specifically, the novel checkpoint inhibitor is approved for patients with ESCC after prior systemic chemotherapy that did not include a programmed death–ligand 1 (PD-L1) inhibitor.
Approval was based on findings from the open-label, phase 3 RATIONALE 302 trial showing a statistically significant and clinically meaningful overall survival benefit with tislelizumab vs investigator’s choice of chemotherapy.
Study participants included 512 adults enrolled at 123 research sites in 11 countries in Europe, Asia, and North America. Patients were randomly assigned to receive intravenous tislelizumab, a humanized immunoglobulin G4 anti-programmed cell death protein 1 monoclonal antibody, at a dose of 200 mg every 3 weeks or investigator’s choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan until disease progression, unacceptable toxicity, or study withdrawal.
Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months vs 6.3 months in the chemotherapy arms (hazard ratio [HR], 0.70). The survival benefit was observed across predefined subgroups, including baseline PD-L1 status and region. The new agent was also associated with improved overall response rate (20.4% vs 9.8%) and more durable response (median duration of response of 7.1 vs 4.0 months; HR, 0.42) compared with chemotherapy.
The most common adverse reactions for tislelizumab, each occurring in at least 20% of treated patients, included increased glucose and decreased hemoglobin, lymphocytes, sodium, and albumin as well as increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
Fewer patients in the tislelizumab arm experienced grade 3 or greater treatment-emergent adverse events compared with the chemotherapy arm (46% vs 68%, respectively), and fewer patients discontinued tislelizumab vs chemotherapy due to such an event (7% vs 14%).
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, MD, of the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, stated in the BeiGene release. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received Tevimbra saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The approval, which was deferred in 2022 due to COVID-19-related restrictions, marks the first for the agent in the United States. Tislelizumab should be available in the United States in the second half of 2024, BeiGene noted.
The FDA is also reviewing a Biologics License Application for the agent as a first-line treatment for patients with unresectable, locally advanced, or metastatic ESCC and for those with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, BeiGene announced in a press release.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved tislelizumab-jsgr (Tevimbra, BeiGene Ltd.) as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Specifically, the novel checkpoint inhibitor is approved for patients with ESCC after prior systemic chemotherapy that did not include a programmed death–ligand 1 (PD-L1) inhibitor.
Approval was based on findings from the open-label, phase 3 RATIONALE 302 trial showing a statistically significant and clinically meaningful overall survival benefit with tislelizumab vs investigator’s choice of chemotherapy.
Study participants included 512 adults enrolled at 123 research sites in 11 countries in Europe, Asia, and North America. Patients were randomly assigned to receive intravenous tislelizumab, a humanized immunoglobulin G4 anti-programmed cell death protein 1 monoclonal antibody, at a dose of 200 mg every 3 weeks or investigator’s choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan until disease progression, unacceptable toxicity, or study withdrawal.
Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months vs 6.3 months in the chemotherapy arms (hazard ratio [HR], 0.70). The survival benefit was observed across predefined subgroups, including baseline PD-L1 status and region. The new agent was also associated with improved overall response rate (20.4% vs 9.8%) and more durable response (median duration of response of 7.1 vs 4.0 months; HR, 0.42) compared with chemotherapy.
The most common adverse reactions for tislelizumab, each occurring in at least 20% of treated patients, included increased glucose and decreased hemoglobin, lymphocytes, sodium, and albumin as well as increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
Fewer patients in the tislelizumab arm experienced grade 3 or greater treatment-emergent adverse events compared with the chemotherapy arm (46% vs 68%, respectively), and fewer patients discontinued tislelizumab vs chemotherapy due to such an event (7% vs 14%).
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, MD, of the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, stated in the BeiGene release. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received Tevimbra saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The approval, which was deferred in 2022 due to COVID-19-related restrictions, marks the first for the agent in the United States. Tislelizumab should be available in the United States in the second half of 2024, BeiGene noted.
The FDA is also reviewing a Biologics License Application for the agent as a first-line treatment for patients with unresectable, locally advanced, or metastatic ESCC and for those with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, BeiGene announced in a press release.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved tislelizumab-jsgr (Tevimbra, BeiGene Ltd.) as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).
Specifically, the novel checkpoint inhibitor is approved for patients with ESCC after prior systemic chemotherapy that did not include a programmed death–ligand 1 (PD-L1) inhibitor.
Approval was based on findings from the open-label, phase 3 RATIONALE 302 trial showing a statistically significant and clinically meaningful overall survival benefit with tislelizumab vs investigator’s choice of chemotherapy.
Study participants included 512 adults enrolled at 123 research sites in 11 countries in Europe, Asia, and North America. Patients were randomly assigned to receive intravenous tislelizumab, a humanized immunoglobulin G4 anti-programmed cell death protein 1 monoclonal antibody, at a dose of 200 mg every 3 weeks or investigator’s choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan until disease progression, unacceptable toxicity, or study withdrawal.
Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months vs 6.3 months in the chemotherapy arms (hazard ratio [HR], 0.70). The survival benefit was observed across predefined subgroups, including baseline PD-L1 status and region. The new agent was also associated with improved overall response rate (20.4% vs 9.8%) and more durable response (median duration of response of 7.1 vs 4.0 months; HR, 0.42) compared with chemotherapy.
The most common adverse reactions for tislelizumab, each occurring in at least 20% of treated patients, included increased glucose and decreased hemoglobin, lymphocytes, sodium, and albumin as well as increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
Fewer patients in the tislelizumab arm experienced grade 3 or greater treatment-emergent adverse events compared with the chemotherapy arm (46% vs 68%, respectively), and fewer patients discontinued tislelizumab vs chemotherapy due to such an event (7% vs 14%).
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, MD, of the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, stated in the BeiGene release. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received Tevimbra saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The approval, which was deferred in 2022 due to COVID-19-related restrictions, marks the first for the agent in the United States. Tislelizumab should be available in the United States in the second half of 2024, BeiGene noted.
The FDA is also reviewing a Biologics License Application for the agent as a first-line treatment for patients with unresectable, locally advanced, or metastatic ESCC and for those with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, BeiGene announced in a press release.
A version of this article appeared on Medscape.com.
New Cancer Surgical Tech Gets Positive Vote, But Some Cite Safety Concerns
A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.
LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.
Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.
“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.
However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.
In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.
“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”
The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.
On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.
“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”
Is the Technology Safe?
Pegulicianine is an imaging agent that contains a fluorescent dye. The agent is given to patients as a 3-minute intravenous infusion 2 to 6 hours before surgery.
After removal of the main tumor specimen, the surgeon inserts a handheld probe into the breast cavity and in combination with the detection software, searches for residual cancer that may have been left behind, Dr. Ferrer explained during the MIDAC meeting.
If the software identifies areas suspicious for residual cancer, those areas display in red on an overhead screen. The surgeon then takes a targeted shave to resect the suspicious tissue. Once the tissue has been removed, the surgeon can rescan the cavity with the probe to ensure a more complete resection has been performed. Use of the LUM system typically takes surgeons less than 7 minutes to use, Dr. Ferrer said.
In the study, a total of 406 patients received the intravenous pegulicianine, but 14 patients were withdrawn before randomization. After a standard lumpectomy procedure, 357 patients were assigned to the pFGS group and 35 patients to the control group.
Of the 406 patients, pegulicianine administration was stopped for adverse events in 6 patients (1.5%). Two patients had grade 3 serious adverse events related to pegulicianine; one had hypersensitivity, and one had an anaphylactic reaction. The other four pegulicianine-related adverse events included allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation.
Dr. Schnabel said these reactions are worrisome. While any effort to reduce the need for patients to have more than one surgery to complete a breast conserving approach would be a “real advance,” Dr. Schnabel said she would not feel comfortable using pFGS in her own practice if approved by the FDA as is.
“This is clearly a major issue in terms of incorporating this technique into practice,” she said. “I could go on, but in light of the above, I’m surprised that [the committee] is supportive. I would hope for some refinement of the technique to reduce the risks to patients and improve the results before I’d consider utilizing this approach.”
During the MIDAC meeting, Dr. Ferrer said the company takes the safety events seriously and has developed mitigation strategies to further reduce the risk of patient hypersensitivity. These strategies include: clear labeling that informs users of anaphylaxis risk, incorporating a new section into the device training program to address warnings and precautions, an enhanced pharmacovigilance program to closely track and report hypersensitivity events, and a postmarket study to access the incidence rate and risk of such events in a broader population.
Several MIDAC members raised questions about the adverse reactions observed and about the safety of the technology.
David B. Hackney, MD, a neuroradiologist at Beth Israel Deaconess Medical Center in Boston, questioned the recommendation that patients only be monitored for 15 minutes after the injection.
“Since you don’t have enough data to know how long after injection reactions could occur, why not keep them under monitoring until after the surgery is over?” he said.
Barbara Smith, MD, PhD, lead investigator of the study, explained that per the protocol, there would be frequent monitoring, with a nurse at bedside, and patients would be monitored after injection, on their way to the procedure, and afterward.
She suggested, during the meeting, that more intense monitoring early in the process would be beneficial as that is when investigators observed side effects believed to be attributed to LUMISIGHT.
MIDAC member Kimberly E. Applegate, MD, a retired radiology professor, asked about the learning curve for surgeons and how long it generally takes for physicians to become familiar with the system.
Coinvestigator Kelly Hunt, MD, explained that all surgeons who participated in the trial completed a training program.
“Certainly, there’s a learning curve anytime we introduce new technology in the operating room,” she said. “Surgeons said it usually takes about three procedures before they’re comfortable with the system, including the camera and the software.”
During a presentation period by FDA officials, Anil Rajpal, MD, MPH, FDA, Deputy Division Director for Safety, said it’s important that prescribing information for LUMISIGHT communicate the risk of anaphylaxis and other hypersensitivity reactions, the need to monitor patients, and the need for the appropriate available personnel, medications, and equipment.
“This would be done by warnings and precautions and a boxed warning,” he said. “Note, that [such warnings] would only communicate the risks, it would not further characterize the risk.”
Committee Expresses Support
During a subsequent vote among committee members, most expressed support for the technology and its benefits. Sixteen members voted in support, one abstained, and two voted against the benefit-risk profile.
Andrea Richardson, MD, PhD, professor of pathology at Johns Hopkins in Baltimore, said she voted yes because the incremental benefits of avoiding additional surgeries outweigh the small risk of anaphylaxis.
Henry Royal, MD, MIDAC chair and professor of radiology at Washington University School of Medicine in St. Louis, agreed.
“Even though the benefit of this is on average, quite small, the benefit to the woman who has positive margins that’s converted to negative margins because of use of [LUMISIGHT] is really quite great,” he said. “The risk from this procedure is certainly very manageable.”
Harold J. Burstein, MD, PhD, a professor of medicine at Harvard Medical School and oncologist at Dana-Farber Cancer Institute in Boston, voted against the benefit-risk profile. He said the technology merits more research and that he does not believe it was proven the technology reduces the risk of reoperation.
“I think it’s a great technology,” he said. “I would like to see a well-conducted, randomized, phase III study with the endpoint of reoperation,” he said. “That would really prove the usefulness and benefit of the intervention in my mind.”
Chengjie Xiong, PhD, professor of biostatistics at Washington University School of Medicine in St. Louis, chose to abstain from voting because he said there was not enough data.
The FDA will now complete its review of Lumicell’s new drug application for LUMISIGHT and review of its premarket approval application for Lumicell DVS. The FDA review team has 6-10 months to make a decision. As part of the process, the FDA will evaluate clinical data, travel to clinical study sites to conduct inspections, and assemble a final action package for a senior FDA official to make a final decision.
If deemed safe and effective, the FDA will then work with Lumicell on developing and refining prescribing information.
Dr. Ferrer said his team expects to receive FDA approval in the coming weeks and will continue to work collaboratively with the FDA to expedite approval where possible.
The purpose of the MIDAC is to review and evaluate data about the safety and effectiveness of marketed and investigational human drug products for use in diagnostic and therapeutic procedures using radioactive pharmaceuticals and make appropriate recommendations to the FDA Commissioner.
A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.
LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.
Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.
“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.
However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.
In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.
“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”
The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.
On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.
“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”
Is the Technology Safe?
Pegulicianine is an imaging agent that contains a fluorescent dye. The agent is given to patients as a 3-minute intravenous infusion 2 to 6 hours before surgery.
After removal of the main tumor specimen, the surgeon inserts a handheld probe into the breast cavity and in combination with the detection software, searches for residual cancer that may have been left behind, Dr. Ferrer explained during the MIDAC meeting.
If the software identifies areas suspicious for residual cancer, those areas display in red on an overhead screen. The surgeon then takes a targeted shave to resect the suspicious tissue. Once the tissue has been removed, the surgeon can rescan the cavity with the probe to ensure a more complete resection has been performed. Use of the LUM system typically takes surgeons less than 7 minutes to use, Dr. Ferrer said.
In the study, a total of 406 patients received the intravenous pegulicianine, but 14 patients were withdrawn before randomization. After a standard lumpectomy procedure, 357 patients were assigned to the pFGS group and 35 patients to the control group.
Of the 406 patients, pegulicianine administration was stopped for adverse events in 6 patients (1.5%). Two patients had grade 3 serious adverse events related to pegulicianine; one had hypersensitivity, and one had an anaphylactic reaction. The other four pegulicianine-related adverse events included allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation.
Dr. Schnabel said these reactions are worrisome. While any effort to reduce the need for patients to have more than one surgery to complete a breast conserving approach would be a “real advance,” Dr. Schnabel said she would not feel comfortable using pFGS in her own practice if approved by the FDA as is.
“This is clearly a major issue in terms of incorporating this technique into practice,” she said. “I could go on, but in light of the above, I’m surprised that [the committee] is supportive. I would hope for some refinement of the technique to reduce the risks to patients and improve the results before I’d consider utilizing this approach.”
During the MIDAC meeting, Dr. Ferrer said the company takes the safety events seriously and has developed mitigation strategies to further reduce the risk of patient hypersensitivity. These strategies include: clear labeling that informs users of anaphylaxis risk, incorporating a new section into the device training program to address warnings and precautions, an enhanced pharmacovigilance program to closely track and report hypersensitivity events, and a postmarket study to access the incidence rate and risk of such events in a broader population.
Several MIDAC members raised questions about the adverse reactions observed and about the safety of the technology.
David B. Hackney, MD, a neuroradiologist at Beth Israel Deaconess Medical Center in Boston, questioned the recommendation that patients only be monitored for 15 minutes after the injection.
“Since you don’t have enough data to know how long after injection reactions could occur, why not keep them under monitoring until after the surgery is over?” he said.
Barbara Smith, MD, PhD, lead investigator of the study, explained that per the protocol, there would be frequent monitoring, with a nurse at bedside, and patients would be monitored after injection, on their way to the procedure, and afterward.
She suggested, during the meeting, that more intense monitoring early in the process would be beneficial as that is when investigators observed side effects believed to be attributed to LUMISIGHT.
MIDAC member Kimberly E. Applegate, MD, a retired radiology professor, asked about the learning curve for surgeons and how long it generally takes for physicians to become familiar with the system.
Coinvestigator Kelly Hunt, MD, explained that all surgeons who participated in the trial completed a training program.
“Certainly, there’s a learning curve anytime we introduce new technology in the operating room,” she said. “Surgeons said it usually takes about three procedures before they’re comfortable with the system, including the camera and the software.”
During a presentation period by FDA officials, Anil Rajpal, MD, MPH, FDA, Deputy Division Director for Safety, said it’s important that prescribing information for LUMISIGHT communicate the risk of anaphylaxis and other hypersensitivity reactions, the need to monitor patients, and the need for the appropriate available personnel, medications, and equipment.
“This would be done by warnings and precautions and a boxed warning,” he said. “Note, that [such warnings] would only communicate the risks, it would not further characterize the risk.”
Committee Expresses Support
During a subsequent vote among committee members, most expressed support for the technology and its benefits. Sixteen members voted in support, one abstained, and two voted against the benefit-risk profile.
Andrea Richardson, MD, PhD, professor of pathology at Johns Hopkins in Baltimore, said she voted yes because the incremental benefits of avoiding additional surgeries outweigh the small risk of anaphylaxis.
Henry Royal, MD, MIDAC chair and professor of radiology at Washington University School of Medicine in St. Louis, agreed.
“Even though the benefit of this is on average, quite small, the benefit to the woman who has positive margins that’s converted to negative margins because of use of [LUMISIGHT] is really quite great,” he said. “The risk from this procedure is certainly very manageable.”
Harold J. Burstein, MD, PhD, a professor of medicine at Harvard Medical School and oncologist at Dana-Farber Cancer Institute in Boston, voted against the benefit-risk profile. He said the technology merits more research and that he does not believe it was proven the technology reduces the risk of reoperation.
“I think it’s a great technology,” he said. “I would like to see a well-conducted, randomized, phase III study with the endpoint of reoperation,” he said. “That would really prove the usefulness and benefit of the intervention in my mind.”
Chengjie Xiong, PhD, professor of biostatistics at Washington University School of Medicine in St. Louis, chose to abstain from voting because he said there was not enough data.
The FDA will now complete its review of Lumicell’s new drug application for LUMISIGHT and review of its premarket approval application for Lumicell DVS. The FDA review team has 6-10 months to make a decision. As part of the process, the FDA will evaluate clinical data, travel to clinical study sites to conduct inspections, and assemble a final action package for a senior FDA official to make a final decision.
If deemed safe and effective, the FDA will then work with Lumicell on developing and refining prescribing information.
Dr. Ferrer said his team expects to receive FDA approval in the coming weeks and will continue to work collaboratively with the FDA to expedite approval where possible.
The purpose of the MIDAC is to review and evaluate data about the safety and effectiveness of marketed and investigational human drug products for use in diagnostic and therapeutic procedures using radioactive pharmaceuticals and make appropriate recommendations to the FDA Commissioner.
A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.
LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.
Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.
“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.
However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.
In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.
“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”
The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.
On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.
“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”
Is the Technology Safe?
Pegulicianine is an imaging agent that contains a fluorescent dye. The agent is given to patients as a 3-minute intravenous infusion 2 to 6 hours before surgery.
After removal of the main tumor specimen, the surgeon inserts a handheld probe into the breast cavity and in combination with the detection software, searches for residual cancer that may have been left behind, Dr. Ferrer explained during the MIDAC meeting.
If the software identifies areas suspicious for residual cancer, those areas display in red on an overhead screen. The surgeon then takes a targeted shave to resect the suspicious tissue. Once the tissue has been removed, the surgeon can rescan the cavity with the probe to ensure a more complete resection has been performed. Use of the LUM system typically takes surgeons less than 7 minutes to use, Dr. Ferrer said.
In the study, a total of 406 patients received the intravenous pegulicianine, but 14 patients were withdrawn before randomization. After a standard lumpectomy procedure, 357 patients were assigned to the pFGS group and 35 patients to the control group.
Of the 406 patients, pegulicianine administration was stopped for adverse events in 6 patients (1.5%). Two patients had grade 3 serious adverse events related to pegulicianine; one had hypersensitivity, and one had an anaphylactic reaction. The other four pegulicianine-related adverse events included allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation.
Dr. Schnabel said these reactions are worrisome. While any effort to reduce the need for patients to have more than one surgery to complete a breast conserving approach would be a “real advance,” Dr. Schnabel said she would not feel comfortable using pFGS in her own practice if approved by the FDA as is.
“This is clearly a major issue in terms of incorporating this technique into practice,” she said. “I could go on, but in light of the above, I’m surprised that [the committee] is supportive. I would hope for some refinement of the technique to reduce the risks to patients and improve the results before I’d consider utilizing this approach.”
During the MIDAC meeting, Dr. Ferrer said the company takes the safety events seriously and has developed mitigation strategies to further reduce the risk of patient hypersensitivity. These strategies include: clear labeling that informs users of anaphylaxis risk, incorporating a new section into the device training program to address warnings and precautions, an enhanced pharmacovigilance program to closely track and report hypersensitivity events, and a postmarket study to access the incidence rate and risk of such events in a broader population.
Several MIDAC members raised questions about the adverse reactions observed and about the safety of the technology.
David B. Hackney, MD, a neuroradiologist at Beth Israel Deaconess Medical Center in Boston, questioned the recommendation that patients only be monitored for 15 minutes after the injection.
“Since you don’t have enough data to know how long after injection reactions could occur, why not keep them under monitoring until after the surgery is over?” he said.
Barbara Smith, MD, PhD, lead investigator of the study, explained that per the protocol, there would be frequent monitoring, with a nurse at bedside, and patients would be monitored after injection, on their way to the procedure, and afterward.
She suggested, during the meeting, that more intense monitoring early in the process would be beneficial as that is when investigators observed side effects believed to be attributed to LUMISIGHT.
MIDAC member Kimberly E. Applegate, MD, a retired radiology professor, asked about the learning curve for surgeons and how long it generally takes for physicians to become familiar with the system.
Coinvestigator Kelly Hunt, MD, explained that all surgeons who participated in the trial completed a training program.
“Certainly, there’s a learning curve anytime we introduce new technology in the operating room,” she said. “Surgeons said it usually takes about three procedures before they’re comfortable with the system, including the camera and the software.”
During a presentation period by FDA officials, Anil Rajpal, MD, MPH, FDA, Deputy Division Director for Safety, said it’s important that prescribing information for LUMISIGHT communicate the risk of anaphylaxis and other hypersensitivity reactions, the need to monitor patients, and the need for the appropriate available personnel, medications, and equipment.
“This would be done by warnings and precautions and a boxed warning,” he said. “Note, that [such warnings] would only communicate the risks, it would not further characterize the risk.”
Committee Expresses Support
During a subsequent vote among committee members, most expressed support for the technology and its benefits. Sixteen members voted in support, one abstained, and two voted against the benefit-risk profile.
Andrea Richardson, MD, PhD, professor of pathology at Johns Hopkins in Baltimore, said she voted yes because the incremental benefits of avoiding additional surgeries outweigh the small risk of anaphylaxis.
Henry Royal, MD, MIDAC chair and professor of radiology at Washington University School of Medicine in St. Louis, agreed.
“Even though the benefit of this is on average, quite small, the benefit to the woman who has positive margins that’s converted to negative margins because of use of [LUMISIGHT] is really quite great,” he said. “The risk from this procedure is certainly very manageable.”
Harold J. Burstein, MD, PhD, a professor of medicine at Harvard Medical School and oncologist at Dana-Farber Cancer Institute in Boston, voted against the benefit-risk profile. He said the technology merits more research and that he does not believe it was proven the technology reduces the risk of reoperation.
“I think it’s a great technology,” he said. “I would like to see a well-conducted, randomized, phase III study with the endpoint of reoperation,” he said. “That would really prove the usefulness and benefit of the intervention in my mind.”
Chengjie Xiong, PhD, professor of biostatistics at Washington University School of Medicine in St. Louis, chose to abstain from voting because he said there was not enough data.
The FDA will now complete its review of Lumicell’s new drug application for LUMISIGHT and review of its premarket approval application for Lumicell DVS. The FDA review team has 6-10 months to make a decision. As part of the process, the FDA will evaluate clinical data, travel to clinical study sites to conduct inspections, and assemble a final action package for a senior FDA official to make a final decision.
If deemed safe and effective, the FDA will then work with Lumicell on developing and refining prescribing information.
Dr. Ferrer said his team expects to receive FDA approval in the coming weeks and will continue to work collaboratively with the FDA to expedite approval where possible.
The purpose of the MIDAC is to review and evaluate data about the safety and effectiveness of marketed and investigational human drug products for use in diagnostic and therapeutic procedures using radioactive pharmaceuticals and make appropriate recommendations to the FDA Commissioner.
Second FDA-Approved Tocilizumab Biosimilar Has Intravenous, Subcutaneous Formulations
The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.
This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release. 
Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:
- Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
- Adults with giant cell arteritis
- Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
- Patients aged 2 years or older with active systemic juvenile idiopathic arthritis
“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.
The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.
Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector.
The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.
Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.
“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.
This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release.
Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:
- Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
- Adults with giant cell arteritis
- Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
- Patients aged 2 years or older with active systemic juvenile idiopathic arthritis
“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.
The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.
Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector.
The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.
Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.
“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the biosimilar tocilizumab-aazg (Tyenne), Fresenius Kabi, the drug’s manufacturer, announced on March 7.
This is the second tocilizumab biosimilar approved by the regulatory agency and the first to be approved in both intravenous (IV) and subcutaneous formulations that are available with the reference product, Actemra, the company said in a press release.
Tocilizumab-aazg is an interleukin-6 (IL-6) receptor antagonist indicated for:
- Adults with moderate to severe rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs
- Adults with giant cell arteritis
- Patients aged 2 years or older with active polyarticular juvenile idiopathic arthritis
- Patients aged 2 years or older with active systemic juvenile idiopathic arthritis
“Fresenius Kabi is leading the way as the first company to receive FDA approval for both IV and subcutaneous formulations of its tocilizumab biosimilar and is available in prefilled syringe, pen injector, and vial presentations,” Fabrice Romanet, senior vice president of innovation and development at Fresenius Kabi Biopharma, said in a statement.
The FDA approved the first tocilizumab biosimilar, manufactured by Biogen, in late September 2023. It is administered by IV infusion.
Tocilizumab-aazg’s approval was based on outcome and safety data from a dozen clinical studies. The drug can be administered via intravenous formulation (20 mg/mL) or subcutaneously via a single-dose 162-mg/0.9-mL prefilled syringe or single-dose prefilled autoinjector.
The most common side effects for tocilizumab-aazg include upper respiratory tract infections, headache, hypertension, and injection site reactions. The most serious side effects include serious infections, perforation of the stomach or intestines, hepatotoxicity, and changes in certain lab results.
Tocilizumab-aazg has already launched in 10 countries, Fresenius Kabi shared in the press release, and plans to launch in additional countries in 2024 and 2025. It is not clear when tocilizumab-aazg will be made available in the United States.
“In accordance with its patent settlement agreement with Genentech, Fresenius Kabi has a license to market its tocilizumab products in the United States commencing on the license dates, which are confidential,” the company noted.
A version of this article appeared on Medscape.com.
Nivolumab Wins First-Line Indication in Metastatic Urothelial Carcinoma
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
TIL for Melanoma: What Are the Costs and Other Challenges to Getting It to Patients?
The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.
Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
Insurance Adjustments
The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.
Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.
Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.
The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.
Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.
At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.
Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.
Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.
Logistics and Infrastructure
A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.
The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
Docs Hope TIL Improves in Several Ways
Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.
More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”
Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.
“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.
“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.
“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”
“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.
In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.
The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.
The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.
The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.
Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
Insurance Adjustments
The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.
Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.
Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.
The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.
Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.
At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.
Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.
Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.
Logistics and Infrastructure
A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.
The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
Docs Hope TIL Improves in Several Ways
Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.
More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”
Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.
“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.
“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.
“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”
“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.
In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.
The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.
The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.
The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.
Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
Insurance Adjustments
The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.
Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.
Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.
The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.
Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.
At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.
Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.
Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.
Logistics and Infrastructure
A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.
The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
Docs Hope TIL Improves in Several Ways
Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.
More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”
Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.
“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.
“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.
“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”
“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.
In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.
The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.
The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.
First Denosumab Biosimilar Approved in Two Different Formulations
The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).
The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February.
The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.
Wyost (120-mg/1.7-mL injection) is approved to:
- Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
- Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
- Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy
Jubbonti (60-mg/1-mL injection) is approved to:
- Treat postmenopausal women with osteoporosis who are at high risk for fracture
- Increase bone mass in men with osteoporosis who are at high risk for fracture
- Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
- Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
- Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.
Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.
Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).
The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February.
The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.
Wyost (120-mg/1.7-mL injection) is approved to:
- Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
- Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
- Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy
Jubbonti (60-mg/1-mL injection) is approved to:
- Treat postmenopausal women with osteoporosis who are at high risk for fracture
- Increase bone mass in men with osteoporosis who are at high risk for fracture
- Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
- Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
- Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.
Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.
Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”
A version of this article appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the first biosimilar to denosumab, denosumab-bddz (Wyost/Jubbonti).
The biosimilar was also granted interchangeability status, which allows pharmacists to substitute the biosimilar for the reference product without involving the prescribing clinician (according to state law). Sandoz announced the approval on March 5, 2024. The lower dosage of denosumab-bddz, marketed as Jubbonti, was also approved by Health Canada in February.
The FDA approval “is based on robust clinical studies and accompanied by labeling with safety warnings,” according to the press release. Like the reference products Prolia and Xgeva, denosumab-bddz is approved for two indications at separate doses.
Wyost (120-mg/1.7-mL injection) is approved to:
- Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
- Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
- Treat hypercalcemia of cancer that is refractory to bisphosphonate therapy
Jubbonti (60-mg/1-mL injection) is approved to:
- Treat postmenopausal women with osteoporosis who are at high risk for fracture
- Increase bone mass in men with osteoporosis who are at high risk for fracture
- Treat glucocorticoid-induced osteoporosis in men and women who are at high risk for fracture
- Increase bone mass in men who are at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer
- Increase bone mass in women who are at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer.
Both doses are contraindicated for hypocalcemia and known clinically significant hypersensitivity to denosumab products. Exposure to denosumab products during pregnancy can cause fetal harm, so women of reproductive potential should be advised to use effective contraception during therapy and for at least 5 months after the last dose of denosumab-bddz.
Sandoz did not provide information on US launch details, citing “ongoing patent litigation around these products.”
A version of this article appeared on Medscape.com.
FDA Approves Amivantamab First-line Indication for NSCLC
Specifically, the FDA approved the first-line use of the agent in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test.
The FDA also granted traditional approval for use in these patients after their cancer has progressed on or following platinum-based chemotherapy. The original accelerated approval for this indication occurred in 2021. At that time, the FDA also approved Guardant360® CDx (Guardant Health, Inc.) as a companion diagnostic test for amivantamab-vmjw.
The first-line approval, which followed priority review, was based on the randomized, open-label PAPILLON trial, which revealed a statistically significant improvement in progression-free survival (PFS) among the 153 patients who received amivantamab-vmjw plus carboplatin and pemetrexed vs the 155 who received the chemotherapy combination alone. Median PFS was 11.4 months in the amivantamab-vmjw arm vs 6.7 months in the control arm (hazard ratio, 0.40).
Data for overall survival, a key secondary endpoint of the study, were immature at the time of the latest analysis, but “no trend toward a detriment was observed,” according to an FDA approval announcement.
Common adverse reactions, occurring in at least 20% of patients in the study, were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, diarrhea, and vomiting. Weight-based dosing guidance can be found in the full prescribing information.
A version of this article appeared on Medscape.com.
Specifically, the FDA approved the first-line use of the agent in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test.
The FDA also granted traditional approval for use in these patients after their cancer has progressed on or following platinum-based chemotherapy. The original accelerated approval for this indication occurred in 2021. At that time, the FDA also approved Guardant360® CDx (Guardant Health, Inc.) as a companion diagnostic test for amivantamab-vmjw.
The first-line approval, which followed priority review, was based on the randomized, open-label PAPILLON trial, which revealed a statistically significant improvement in progression-free survival (PFS) among the 153 patients who received amivantamab-vmjw plus carboplatin and pemetrexed vs the 155 who received the chemotherapy combination alone. Median PFS was 11.4 months in the amivantamab-vmjw arm vs 6.7 months in the control arm (hazard ratio, 0.40).
Data for overall survival, a key secondary endpoint of the study, were immature at the time of the latest analysis, but “no trend toward a detriment was observed,” according to an FDA approval announcement.
Common adverse reactions, occurring in at least 20% of patients in the study, were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, diarrhea, and vomiting. Weight-based dosing guidance can be found in the full prescribing information.
A version of this article appeared on Medscape.com.
Specifically, the FDA approved the first-line use of the agent in combination with carboplatin and pemetrexed in patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test.
The FDA also granted traditional approval for use in these patients after their cancer has progressed on or following platinum-based chemotherapy. The original accelerated approval for this indication occurred in 2021. At that time, the FDA also approved Guardant360® CDx (Guardant Health, Inc.) as a companion diagnostic test for amivantamab-vmjw.
The first-line approval, which followed priority review, was based on the randomized, open-label PAPILLON trial, which revealed a statistically significant improvement in progression-free survival (PFS) among the 153 patients who received amivantamab-vmjw plus carboplatin and pemetrexed vs the 155 who received the chemotherapy combination alone. Median PFS was 11.4 months in the amivantamab-vmjw arm vs 6.7 months in the control arm (hazard ratio, 0.40).
Data for overall survival, a key secondary endpoint of the study, were immature at the time of the latest analysis, but “no trend toward a detriment was observed,” according to an FDA approval announcement.
Common adverse reactions, occurring in at least 20% of patients in the study, were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, diarrhea, and vomiting. Weight-based dosing guidance can be found in the full prescribing information.
A version of this article appeared on Medscape.com.
Omalizumab for Food Allergies: What PCPs Should Know
Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies.
Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.
Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.
While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions.
An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.
The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.
Patient Selection Key
While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.
“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”
Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.”
Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.
“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.
Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.
“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”
Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.
For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.
“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said.
Managing Potential Harms
Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said.
Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said.
Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”
The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.
Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.
Lifelong Treatment
Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.
Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.
Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said.
Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.
“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies.
Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.
Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.
While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions.
An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.
The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.
Patient Selection Key
While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.
“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”
Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.”
Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.
“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.
Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.
“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”
Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.
For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.
“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said.
Managing Potential Harms
Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said.
Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said.
Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”
The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.
Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.
Lifelong Treatment
Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.
Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.
Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said.
Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.
“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies.
Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.
Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.
While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions.
An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.
The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.
Patient Selection Key
While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.
“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”
Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.”
Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.
“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.
Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.
“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”
Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.
For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.
“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said.
Managing Potential Harms
Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said.
Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said.
Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”
The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.
Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.
Lifelong Treatment
Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.
Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.
Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said.
Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.
“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FDA Removes Harmful Chemicals From Food Packaging
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.