User login
FDA expands list of Getinge IABP system and component shortages
The U.S. Food and Drug Administration issued a letter to health care providers describing a current shortage of Getinge intra-aortic balloon pump (IABP) catheters and other components.
Earlier, the agency announced shortages of the company’s Maquet/Datascope IAB catheters, new Cardiosave IABP devices, and Cardiosave IABP parts. The new notification adds Getinge Maquet/Datascope IABP systems to the list.
The company’s letter explains that “ongoing supply chain issues have significantly impacted our ability to build intra-aortic balloon pumps, intra-aortic balloon catheters, and spare parts due to raw material shortages.”
It also offers guidance on maintaining Cardiosave Safety Disks and lithium-ion batteries in the face of the shortages. “In the event that you need a replacement pump while your IABP is undergoing service, please contact your local sales representative who may be able to assist with a temporary IABP.”
Providers are instructed to inform the company through its sales representatives “if you have any underutilized Maquet/Datascope IAB catheters or IABPs and are willing to share them with hospitals in need.”
The shortages are expected to continue into 2023, the FDA states in its letter.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration issued a letter to health care providers describing a current shortage of Getinge intra-aortic balloon pump (IABP) catheters and other components.
Earlier, the agency announced shortages of the company’s Maquet/Datascope IAB catheters, new Cardiosave IABP devices, and Cardiosave IABP parts. The new notification adds Getinge Maquet/Datascope IABP systems to the list.
The company’s letter explains that “ongoing supply chain issues have significantly impacted our ability to build intra-aortic balloon pumps, intra-aortic balloon catheters, and spare parts due to raw material shortages.”
It also offers guidance on maintaining Cardiosave Safety Disks and lithium-ion batteries in the face of the shortages. “In the event that you need a replacement pump while your IABP is undergoing service, please contact your local sales representative who may be able to assist with a temporary IABP.”
Providers are instructed to inform the company through its sales representatives “if you have any underutilized Maquet/Datascope IAB catheters or IABPs and are willing to share them with hospitals in need.”
The shortages are expected to continue into 2023, the FDA states in its letter.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration issued a letter to health care providers describing a current shortage of Getinge intra-aortic balloon pump (IABP) catheters and other components.
Earlier, the agency announced shortages of the company’s Maquet/Datascope IAB catheters, new Cardiosave IABP devices, and Cardiosave IABP parts. The new notification adds Getinge Maquet/Datascope IABP systems to the list.
The company’s letter explains that “ongoing supply chain issues have significantly impacted our ability to build intra-aortic balloon pumps, intra-aortic balloon catheters, and spare parts due to raw material shortages.”
It also offers guidance on maintaining Cardiosave Safety Disks and lithium-ion batteries in the face of the shortages. “In the event that you need a replacement pump while your IABP is undergoing service, please contact your local sales representative who may be able to assist with a temporary IABP.”
Providers are instructed to inform the company through its sales representatives “if you have any underutilized Maquet/Datascope IAB catheters or IABPs and are willing to share them with hospitals in need.”
The shortages are expected to continue into 2023, the FDA states in its letter.
A version of this article first appeared on Medscape.com.
FDA pulls U.S. authorization for Eli Lilly’s COVID drug bebtelovimab
the Food and Drug Administration said, citing it is not expected to neutralize the dominant BQ.1 and BQ.1.1 subvariants of Omicron.
The announcement on Nov. 30 takes away authorization from the last COVID-19 monoclonal antibody treatment, leaving Pfizer’s antiviral drug Paxlovid, Merck’s Lagevrio, and Gilead Sciences’ Veklury as treatments for the disease, besides convalescent plasma for some patients.
AstraZeneca’s monoclonal antibody Evusheld is also authorized for protection against COVID-19 infection in some people.
Eli Lilly and its authorized distributors have paused commercial distribution of the monoclonal antibody until further notice from the agency, while the U.S. government has also paused fulfillment of any pending requests under its scheme to help uninsured and underinsured Americans access the drug.
The drug, which was discovered by Abcellera and commercialized by Eli Lilly, received an authorization from the FDA in February.
BQ.1 and BQ.1.1 have become the dominant strains in the United States after a steady increase in prevalence over the last 2 months, surpassing Omicron’s BA.5 subvariant, which had driven cases earlier in the year.
The subvariants accounted for around 57% of the cases nationally, as per government data last week.
Reuters Health Information © 2022
the Food and Drug Administration said, citing it is not expected to neutralize the dominant BQ.1 and BQ.1.1 subvariants of Omicron.
The announcement on Nov. 30 takes away authorization from the last COVID-19 monoclonal antibody treatment, leaving Pfizer’s antiviral drug Paxlovid, Merck’s Lagevrio, and Gilead Sciences’ Veklury as treatments for the disease, besides convalescent plasma for some patients.
AstraZeneca’s monoclonal antibody Evusheld is also authorized for protection against COVID-19 infection in some people.
Eli Lilly and its authorized distributors have paused commercial distribution of the monoclonal antibody until further notice from the agency, while the U.S. government has also paused fulfillment of any pending requests under its scheme to help uninsured and underinsured Americans access the drug.
The drug, which was discovered by Abcellera and commercialized by Eli Lilly, received an authorization from the FDA in February.
BQ.1 and BQ.1.1 have become the dominant strains in the United States after a steady increase in prevalence over the last 2 months, surpassing Omicron’s BA.5 subvariant, which had driven cases earlier in the year.
The subvariants accounted for around 57% of the cases nationally, as per government data last week.
Reuters Health Information © 2022
the Food and Drug Administration said, citing it is not expected to neutralize the dominant BQ.1 and BQ.1.1 subvariants of Omicron.
The announcement on Nov. 30 takes away authorization from the last COVID-19 monoclonal antibody treatment, leaving Pfizer’s antiviral drug Paxlovid, Merck’s Lagevrio, and Gilead Sciences’ Veklury as treatments for the disease, besides convalescent plasma for some patients.
AstraZeneca’s monoclonal antibody Evusheld is also authorized for protection against COVID-19 infection in some people.
Eli Lilly and its authorized distributors have paused commercial distribution of the monoclonal antibody until further notice from the agency, while the U.S. government has also paused fulfillment of any pending requests under its scheme to help uninsured and underinsured Americans access the drug.
The drug, which was discovered by Abcellera and commercialized by Eli Lilly, received an authorization from the FDA in February.
BQ.1 and BQ.1.1 have become the dominant strains in the United States after a steady increase in prevalence over the last 2 months, surpassing Omicron’s BA.5 subvariant, which had driven cases earlier in the year.
The subvariants accounted for around 57% of the cases nationally, as per government data last week.
Reuters Health Information © 2022
FDA approves olutasidenib for some AML patients
Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.
The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.
Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.
About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.
“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.
This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.
Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).
The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).
Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”
The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.
Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.
In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.
In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.
Further details are available in the full prescribing information.
A version of this article first appeared on Medscape.com.
Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.
The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.
Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.
About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.
“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.
This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.
Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).
The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).
Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”
The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.
Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.
In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.
In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.
Further details are available in the full prescribing information.
A version of this article first appeared on Medscape.com.
Specifically, the drug is approved for use in patients who have R/R AML with a susceptible isocitrate dehydrogenase 1 (IDH1) mutation as detected by an FDA-approved test.
The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment.
Olutasidenib is an oral inhibitor of mutated IDH1 that has been designed to bind and inhibit mutated IDH1 to reduce hydroxyglutarate levels and restore cellular differentiation of myeloid cells, says the manufacturer, Rigel.
About half of all patients with AML have relapse after treatment and remission, and about 10%-40% have refractory cases and do not achieve remission even after intensive treatment, the company noted.
“Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, olutasidenib may provide an effective new treatment option with a well-characterized safety profile,” Jorges Cortes, MD, director of the Georgia Cancer Center, Augusta, commented in the company press release. He was an investigator on the phase 2 trial that led to the drug’s approval.
This was Study 2102-HEM-101 (NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay.
Olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (performed in 16 patients [11%]). The median treatment duration was 4.7 months (range, 0.1-26 months).
The FDA noted that efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval, 27%-43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).
Commenting on these results in the company statement, Dr. Cortes noted that among the patients who responded, more than 90% were experiencing incomplete remission. He added that the “25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options.”
The FDA also noted that among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during any 56-day postbaseline period.
Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day post-baseline period.
The most common adverse reactions (≥ 20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information contains a boxed warning about the risk for differentiation syndrome, which can be fatal.
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal, the company explained. Symptoms may include leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain.
In the trial, differentiation syndrome was observed in 16% of patients, with grade 3 or 4 occurring in 8% of patients treated and death in 1% of patients. It occurred as early as 1 day and up to 18 months after starting treatment.
In most cases, differentiation syndrome was manageable with dose interruption and corticosteroids, the company said. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption.
Further details are available in the full prescribing information.
A version of this article first appeared on Medscape.com.
FDA requests more restrictions on ovarian cancer drugs
citing recent data showing an increased risk for death with the agents versus chemotherapy.
These restrictions could mean bankruptcy for one company.
Earlier this year, several companies voluntarily withdrew their respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.
Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.
The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.
On Nov. 11, GSK announced that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.
The prescribing change was based on an FDA review of the final overall survival analysis of the NOVA phase 3 trial, which served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.
The company noted, however, that its first-line indication remains unchanged.
The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S. Securities and Exchange Commission filing from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.
According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy.
In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA. According to the company, among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”
Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.
Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.
However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an earlier report, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”
The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”
The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”
A version of this article first appeared on Medscape.com.
citing recent data showing an increased risk for death with the agents versus chemotherapy.
These restrictions could mean bankruptcy for one company.
Earlier this year, several companies voluntarily withdrew their respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.
Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.
The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.
On Nov. 11, GSK announced that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.
The prescribing change was based on an FDA review of the final overall survival analysis of the NOVA phase 3 trial, which served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.
The company noted, however, that its first-line indication remains unchanged.
The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S. Securities and Exchange Commission filing from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.
According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy.
In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA. According to the company, among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”
Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.
Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.
However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an earlier report, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”
The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”
The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”
A version of this article first appeared on Medscape.com.
citing recent data showing an increased risk for death with the agents versus chemotherapy.
These restrictions could mean bankruptcy for one company.
Earlier this year, several companies voluntarily withdrew their respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.
Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.
The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.
On Nov. 11, GSK announced that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.
The prescribing change was based on an FDA review of the final overall survival analysis of the NOVA phase 3 trial, which served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.
The company noted, however, that its first-line indication remains unchanged.
The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S. Securities and Exchange Commission filing from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.
According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to platinum-based chemotherapy.
In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA. According to the company, among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”
Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.
Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.
However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an earlier report, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”
The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”
The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”
A version of this article first appeared on Medscape.com.
FDA rejects poziotinib for certain types of lung cancer
The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.
The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.
Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.
Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”
“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals.
However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
Drug development criticized
At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”
The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.
To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.
The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.
Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.
“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.
Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.
Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.
Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.
“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time.
A version of this article first appeared on Medscape.com.
The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.
The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.
Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.
Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”
“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals.
However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
Drug development criticized
At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”
The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.
To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.
The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.
Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.
“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.
Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.
Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.
Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.
“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time.
A version of this article first appeared on Medscape.com.
The clinical data the company submitted were deemed insufficient for approval, and additional data including a randomized clinical trial would be needed, the agency said.
The move is not a surprise, as the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 against approval when it met to discuss the drug in September, as reported at the time by this news organization.
Poziotinib was developed for patients with previously treated locally advanced or metastatic NSCLC harboring HER2 exon 20 insertion mutations, which occur in about 2% of patients with NSCLC.
Poziotinib is a potent oral pan-HER tyrosine kinase inhibitor with activity in patients with these mutations. Clinical data from the ZENITH20 Trial reported last year showed an overall response rate of 43.8%, and the drug was described as showing “clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.”
“We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed,” commented Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals.
However, following multiple interactions with the FDA, “we have made the strategic decision to immediately deprioritize the poziotinib program,” he said. The change is effective immediately, and the company is now in the process of reducing its R&D workforce by approximately 75%.
Drug development criticized
At the ODAC meeting, several panelists were openly critical of the approach Spectrum took in developing the drug. The FDA’s top cancer official, Richard Pazdur, MD, characterized Spectrum’s work as “poor drug development” and likened it to “building a house on quicksand.”
The FDA panel detailed several ways they felt that the poziotinib application fell short of the benchmarks needed for accelerated approval.
To win such a speedy clearance, a company needs to show that a drug provides a meaningful therapeutic benefit over existing treatments. The panel argued that, so far, poziotinib appears to be inferior to a product already available for HER2-mutant NSCLC, trastuzumab deruxtecan (Enhertu), which received accelerated approval in August.
The FDA staff contrasted a reported overall response rate for poziotinib, which was estimated at 28% (from data discussed at the meeting), with the overall response rate for trastuzumab deruxtecan, which is 58%.
Harpreet Singh, MD, a director in the FDA’s oncology division, asked the panel to consider what they would do as a physician treating a patient with this mutation, given the choices that are now available.
“That’s something we’re asking the committee to consider … to think about the context of what’s available to you in the clinic,” Dr. Singh said.
Dr. Singh said she expected that patients and physicians would prefer a drug such as trastuzumab deruxtecan, which has a more established record, regardless of the fact that treatment with poziotinib is more convenient because it is given as a tablet.
Dr. Singh and other staff also raised concerns about side effects of poziotinib, including diarrhea, as well as difficulty determining the right dose.
Katherine Scilla, MD, one of the nine ODAC panelists to vote “no,” echoed these views. Although Dr. Scilla, an oncologist at the University of Maryland, Baltimore, sympathized with the need for options for people with this rare form of lung cancer, she was not persuaded by the data on poziotinib that were presented to support accelerated approval.
“I’m not sure that this represents a meaningful therapeutic benefit over other agents,” she said at the time.
A version of this article first appeared on Medscape.com.
Atezolizumab (Tecentriq) bladder cancer indication withdrawn in United States
The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.
The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
The company said that it made the decision after consultation with the Food and Drug Administration.
“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.
Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.
The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”
The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.
Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.
These data will be presented at an upcoming medical meeting, the company added.
“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.
A version of this article first appeared on Medscape.com.
The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.
The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
The company said that it made the decision after consultation with the Food and Drug Administration.
“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.
Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.
The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”
The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.
Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.
These data will be presented at an upcoming medical meeting, the company added.
“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.
A version of this article first appeared on Medscape.com.
The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.
The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
The company said that it made the decision after consultation with the Food and Drug Administration.
“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.
Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.
The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”
The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.
Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.
These data will be presented at an upcoming medical meeting, the company added.
“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.
A version of this article first appeared on Medscape.com.
FDA OKs first fecal transplant therapy for recurrent C. difficile
Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.
“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.
As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.
A panel of FDA advisors recommended approval of Rebyota in September.
The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
A vicious cycle
Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.
Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.
Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.
The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.
In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.
The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.
Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.
The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.
“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.
Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.
However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.
Full prescribing information for Rebyota is available online.
Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.
“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.
As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.
A panel of FDA advisors recommended approval of Rebyota in September.
The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
A vicious cycle
Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.
Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.
Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.
The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.
In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.
The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.
Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.
The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.
“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.
Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.
However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.
Full prescribing information for Rebyota is available online.
Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.
“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.
As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.
A panel of FDA advisors recommended approval of Rebyota in September.
The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
A vicious cycle
Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.
Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.
Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.
The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.
In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.
The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.
Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.
The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.
“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.
Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.
However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.
Full prescribing information for Rebyota is available online.
Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
With type 1 diabetes delay possible, focus now on screening
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
The recent approval of teplizumab-mzwv (Tzield, Provention Bio) for the delay of type 1 diabetes by the Food and Drug Administration is expected to advance efforts to increase screening to cost effectively identify those at risk for the condition who would be eligible to receive the new treatment.
The anti-CD3 monoclonal antibody was approved Nov. 17 as the first disease-modifying therapy for impeding progression of type 1 diabetes. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.
It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment.
The specific indication is “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes.” In stage 2 type 1 diabetes, the individual has two or more islet autoantibodies and abnormal glycemia but is as yet asymptomatic. It is associated with a nearly 100% lifetime risk of progression to clinical (stage 3) type 1 diabetes and a 75% risk of developing the condition within 5 years.
Currently, most people who are screened for type 1 diabetes autoantibodies are first-degree relatives of those with the condition through TrialNet, other local programs, or more recently, a $55 test offered by the research and advocacy organization JDRF.
But because 85%-90% of people who develop type 1 diabetes don’t have first-degree relatives with the condition, broader population screening will be necessary to identify eligible candidates for teplizumab.
During an investor call on Nov. 18, Provention Bio chief commercial officer Jason Hoitt said that among the company’s “strategic initiatives” were “advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population,” as well as “[health care provider] belief in teplizumab and desire to prescribe it for their patients.”
Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Mr. Hoitt said, adding, “with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed.”
During the call, Mr. Hoitt also announced that the wholesale acquisition cost of Tzield would be $13,850 per vial, which translates to $193,900 per 14-vial continuous regimen, anticipated to be a sufficient dose for most patients. The company also launched a program called COMPASS to help patients navigate insurance reimbursement, as well as provide some with financial assistance.
Cost aside, JDRF CEO Aaron Kowalski, PhD, said in an interview that clinicians shouldn’t doubt the value of delaying type 1 diabetes onset, even if not completely preventing it. “This is the first drug ever to treat the underlying disease. There is this undercurrent that insulin is enough. Why would you undertake an additional risk of an immunotherapy? Type 1 is hard to live with. I think sometimes the clinical community doesn’t appreciate that insulin is not enough. It’s very difficult, and opening this door is important. ... We believe very strongly that the delay of onset of type 1 diabetes is clinically meaningful. We hear that from every family we’ve talked to. Clinicians should appreciate this and not discount it.”
How would screening happen?
While the path to universal screening for type 1 diabetes risk isn’t yet clear, quite a bit of thought and research has gone into it even before teplizumab and other immune-modulating agents showed promise in forestalling the condition.
Data from a universal screening program of schoolchildren implemented in Bavaria, Germany, and a screening program in Denver, suggest that even without such an intervention, identifying people at high risk for developing type 1 diabetes could be cost effective by allowing for education of the individual and family members about the signs of type 1 diabetes, thereby reducing the likelihood that the person would progress to developing diabetic ketoacidosis (DKA) prior to diagnosis.
Another study that used data from the United States and Western Europe, found that screening children for type 1 diabetes–associated islet autoantibodies at ages 2 and 6 years would identify most of those who go on to develop the disease by midadolescence.
However, using a genetic risk score at birth to identify those who would go on to autoantibody testing is potentially a more cost-effective approach, William A. Hagopian, MD, PhD, director of diabetes programs, Pacific Northwest Research Institute, Seattle, said in an interview.
The score – based on human leukocyte antigen haplotypes and their interactions as well as non-HLA genes – can stratify nearly 80% of childhood type 1 diabetes within the top 10% of all newborns. Thus, only the top 10% would then go on to receive the more expensive autoantibody testing.
“I’ve been working with U.K. colleagues for the past 3-4 years to develop a strategy using genetic risk scores followed by autoantibody screening. I feel strongly that that’s the cost-effective way to go. It’s relatively inexpensive, scalable, and can be applied commercially in newborn screening labs. To be successful an approach must be cost effective. Payors are willing to pay for newborn screening, but not so much on testing 100% of kids for antibodies,” Dr. Hagopian said.
He is now working with Washington State newborn screening labs to demonstrate feasibility of the approach using dried blood samples from actual neonatal screening after obtaining informed consent from the mothers in postpartum wards in several hospitals. Those found to be at high risk using the genetic risk score are contacted for follow-up with autoantibody screening. The program will continue for another year and a half. “I think it actually has a chance of being accepted into their regular program,” he said.
And then, he hopes, other states will follow, and eventually, the strategy will be added to the Recommended Uniform Screening Panel for universal newborn screening programs, as recommended by the Department of Health & Human Services.
“New newborn screenings for additional diseases are implemented regularly,” Dr. Hagopian said. “Most are far less common than type 1 diabetes. So even if our approach is less than 100% sensitive, this condition is a lot more common than the many inborn errors of metabolism, so we’re still going to be identifying a lot of cases. ... This is my hope for how universal type 1 diabetes screening will unfold. I see a way this may work quite well.”
A two-pronged approach to screening could work best
Meanwhile, JDRF, which supported the teplizumab research as well as others working in the space, is focusing on both genetic and autoantibody screening, Dr. Kowalski said.
“JDRF is working on both pathways – testing kids at birth for genetic predisposition and also antibody screening. We have huge programs focused on general population antibody screening.”
Dr. Kowalski said that, while the two-pronged approach certainly is worth exploring – and JDRF is doing that – he also thinks that universal autoantibody screening could be cost effective if done efficiently, such as with less expensive assays than the one used in TrialNet.
“We have programs where you do the genetic screening and keep an eye on people. We also have programs, like the one we’re funding in Germany, that are doing broad autoantibody screening of all kids. We’re hopeful that will be very cost effective if we move to cheaper assays.”
He noted that the proportion of children with new-onset type 1 diabetes who present in DKA rose from 40% pre–COVID-19 to 50% during the early days of the pandemic. On the other hand, “With screening you can get that to near zero, like they did in Bavaria. Here [in the United States], one ICU visit for DKA [costs] $100,000.”
While JDRF and others have been working on this for years, the new availability of teplizumab will be “multifold in helping things along. ... I think you’re going to see a lot of work on the cost-effectiveness of teplizumab. I think the case will be pretty straightforward that there’s huge upside to delaying the disease from a near-term and a long-term cost perspective. This is the first time we’ve had a drug out there with a price attached to it.”
But it may not happen quickly, Kowalski cautioned. “I feel there’s a ... series of events that has to happen to drive towards universal screening. Here in the U.S. it’s complicated because we have a very discrepant health care system with all these different payers, public and private.”
During the investor call, Mr. Hoitt said that Provention Bio is also exploring use of Tzield in younger patients and newly diagnosed patients, and the potential benefit of redosing or combining with other treatments.
Mr. Hoitt is an employee of Provention Bio. Dr. Kowalski is an employee of JDRF. Dr. Hagopian has reported receiving study funding from Janssen.
A version of this article first appeared on Medscape.com.
FDA alert: ‘Substantial’ hypocalcemia risk with denosumab use in dialysis patients
The Food and Drug Administration issued an alert on Nov. 22 that cited preliminary evidence for a “substantial risk” for severe and symptomatic hypocalcemia and serious outcomes related to abnormally low calcium levels in people being treated with dialysis and receiving the osteoporosis medication denosumab (Prolia), including hospitalization and death.
In its alert, the FDA advised clinicians to make sure that people on dialysis who receive Prolia ingest adequate calcium and vitamin D supplementation and undergo frequent blood calcium monitoring, “possibly more often than is already being conducted,” which “may help decrease the likelihood or severity of these risks.”
The agency also called on clinicians to “advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia,” such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.
The FDA had a similar message for people being treated with dialysis who are also receiving Prolia. The alert advised patients to watch for these symptoms and to tell their health care provider if they occur. The agency also advised patients who are undergoing dialysis and receiving Prolia to not stop the agent on their own, without first discussing this step with their care provider.
The FDA also advised providers and patients to contact the agency about episodes of side effects from Prolia (or other medications) via the FDA’s MedWatch program.
Frequent and serious
The FDA explained it issued the alert because of “the frequency and seriousness” of the risk for hypocalcemia and resulting complications. The agency noted that the risk seems most acute for people on dialysis who also receive Prolia, but the risk may also extend to people with advanced kidney disease who are not being treated with hemodialysis.
The alert stemmed from “interim results” in an ongoing safety study of Prolia that the FDA required the agent’s manufacturer, Amgen, to run when the agency first approved denosumab for U.S. marketing in 2010. The FDA said its review of these interim results suggested an increased risk of hypocalcemia with Prolia in patients with advanced kidney disease.
In addition, adverse event reports submitted to the FDA suggested in a separate, internal study that patients on dialysis treated with Prolia are at “substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.”
The alert explained that “because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis.” The FDA added that “we will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration issued an alert on Nov. 22 that cited preliminary evidence for a “substantial risk” for severe and symptomatic hypocalcemia and serious outcomes related to abnormally low calcium levels in people being treated with dialysis and receiving the osteoporosis medication denosumab (Prolia), including hospitalization and death.
In its alert, the FDA advised clinicians to make sure that people on dialysis who receive Prolia ingest adequate calcium and vitamin D supplementation and undergo frequent blood calcium monitoring, “possibly more often than is already being conducted,” which “may help decrease the likelihood or severity of these risks.”
The agency also called on clinicians to “advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia,” such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.
The FDA had a similar message for people being treated with dialysis who are also receiving Prolia. The alert advised patients to watch for these symptoms and to tell their health care provider if they occur. The agency also advised patients who are undergoing dialysis and receiving Prolia to not stop the agent on their own, without first discussing this step with their care provider.
The FDA also advised providers and patients to contact the agency about episodes of side effects from Prolia (or other medications) via the FDA’s MedWatch program.
Frequent and serious
The FDA explained it issued the alert because of “the frequency and seriousness” of the risk for hypocalcemia and resulting complications. The agency noted that the risk seems most acute for people on dialysis who also receive Prolia, but the risk may also extend to people with advanced kidney disease who are not being treated with hemodialysis.
The alert stemmed from “interim results” in an ongoing safety study of Prolia that the FDA required the agent’s manufacturer, Amgen, to run when the agency first approved denosumab for U.S. marketing in 2010. The FDA said its review of these interim results suggested an increased risk of hypocalcemia with Prolia in patients with advanced kidney disease.
In addition, adverse event reports submitted to the FDA suggested in a separate, internal study that patients on dialysis treated with Prolia are at “substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.”
The alert explained that “because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis.” The FDA added that “we will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration issued an alert on Nov. 22 that cited preliminary evidence for a “substantial risk” for severe and symptomatic hypocalcemia and serious outcomes related to abnormally low calcium levels in people being treated with dialysis and receiving the osteoporosis medication denosumab (Prolia), including hospitalization and death.
In its alert, the FDA advised clinicians to make sure that people on dialysis who receive Prolia ingest adequate calcium and vitamin D supplementation and undergo frequent blood calcium monitoring, “possibly more often than is already being conducted,” which “may help decrease the likelihood or severity of these risks.”
The agency also called on clinicians to “advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia,” such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.
The FDA had a similar message for people being treated with dialysis who are also receiving Prolia. The alert advised patients to watch for these symptoms and to tell their health care provider if they occur. The agency also advised patients who are undergoing dialysis and receiving Prolia to not stop the agent on their own, without first discussing this step with their care provider.
The FDA also advised providers and patients to contact the agency about episodes of side effects from Prolia (or other medications) via the FDA’s MedWatch program.
Frequent and serious
The FDA explained it issued the alert because of “the frequency and seriousness” of the risk for hypocalcemia and resulting complications. The agency noted that the risk seems most acute for people on dialysis who also receive Prolia, but the risk may also extend to people with advanced kidney disease who are not being treated with hemodialysis.
The alert stemmed from “interim results” in an ongoing safety study of Prolia that the FDA required the agent’s manufacturer, Amgen, to run when the agency first approved denosumab for U.S. marketing in 2010. The FDA said its review of these interim results suggested an increased risk of hypocalcemia with Prolia in patients with advanced kidney disease.
In addition, adverse event reports submitted to the FDA suggested in a separate, internal study that patients on dialysis treated with Prolia are at “substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.”
The alert explained that “because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis.” The FDA added that “we will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”
A version of this article first appeared on Medscape.com.
FDA approves first gene therapy for hemophilia B
“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”
Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.
The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.
Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.
Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.
Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.
Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.
The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.
Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.
This article was updated 11/23/22.
Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.
“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”
Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.
The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.
Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.
Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.
Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.
Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.
The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.
Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.
This article was updated 11/23/22.
Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.
“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”
Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.
The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.
Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.
Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.
Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.
Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.
The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.
Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.
This article was updated 11/23/22.
Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.