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Public Citizen seeks stronger warning for Botox, related products
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The nonprofit watchdog group successfully petitioned the FDA in 2008 to require a warning for Botox and related products regarding the risk of distant spread of the toxin. In its latest petition to the agency, it says that the injectables need additional warnings about the possibility of iatrogenic botulism with initial and repeated doses and that individuals who contract the condition may need botulinum antitoxin to avert temporary muscle paralysis, hospitalization, and death.
The current warning does not contain any information about the potential need for antitoxin and downplays the need for giving antitoxin in the settings of excessive dosing, accidental injection, and oral ingestion, said Public Citizen.
“Our petition is based on clear postmarketing evidence that refutes industry propaganda claiming that Botox and related drugs are ‘always safe’ and that no ‘definitive’ cases of botulism have occurred with recommended doses,” Azza AbuDagga, PhD, health services researcher at Public Citizen’s Health Research Group, said in a statement.
Public Citizen said that using data from the FDA’s Adverse Event Reporting System (FAERS), it found 5414 reports of serious outcomes from botulinum toxin products from January 1989 through March 2021. Almost 22% involved cosmetic indications and about 78% involved therapeutic indications.
Of the 5414 reports, 121 (2%) specified botulism as an adverse reaction; 89 involved therapeutic uses of a botulinum toxin products, and 32 involved cosmetic uses. Many of those 121 reports involved doses within the recommended range for the indication, according to Public Citizen.
The group is also asking the FDA to remove what it calls misleading promotional statements in the labeling of Botox and Botox Cosmetic and from the medication guides for those products. The labels state that there have been “no definitive serious adverse event reports of distant spread of toxin effect” with either the cosmetic use or for use in treating chronic migraine, severe underarm sweating, blepharospasm, or strabismus. These statements do not appear in similar labeling in other countries, such as Canada and the United Kingdom, said Public Citizen.
“The FDA needs to implement our two requested actions quickly to warn the public in unambiguous terms about the risk of botulism associated with the use of Botox and related drugs,” Dr. AbuDagga said in the Public Citizen statement. “This will allow health care professionals and patients to make more informed decisions about the benefit-risk profile of these widely used drugs.”
The Public Citizen petition would apply to all seven approved botulinum toxin biological products: abobotulinumtoxinA (Dysport), daxibotulinumtoxinA-lanm (Daxxify), incobotulinumtoxinA (Xeomin), onabotulinumtoxinA (Botox, Botox Cosmetic), prabotulinumtoxinA-xvfs (Jeuveau) and rimabotulinumtoxinB (Myobloc).
An FDA spokesperson said the agency is reviewing the citizen petition, and that generally the agency does not comment on pending petitions. “When we respond to the petition, we will respond directly to the petitioner and post the response in the designated agency docket,” the spokesperson told this news organization. At press time, Botox manufacturer AbbVie had not responded to a request for a comment.
Botulinum toxin is the most-used product for nonsurgical cosmetic procedures, according to the International Society of Aesthetic Plastic Surgery (ISAPS). The ISAPS reported that there were more than 7 million botulinum toxin procedures performed by plastic surgeons worldwide in 2021.
The American Society of Plastic Surgery reported that its members performed 4.4 million Botox procedures in 2020, while the American Society of Dermatologic Surgery (ASDS) said its members performed 2.3 million wrinkle-relaxing procedures in 2019, a 60% increase since 2012.
.
The nonprofit watchdog group successfully petitioned the FDA in 2008 to require a warning for Botox and related products regarding the risk of distant spread of the toxin. In its latest petition to the agency, it says that the injectables need additional warnings about the possibility of iatrogenic botulism with initial and repeated doses and that individuals who contract the condition may need botulinum antitoxin to avert temporary muscle paralysis, hospitalization, and death.
The current warning does not contain any information about the potential need for antitoxin and downplays the need for giving antitoxin in the settings of excessive dosing, accidental injection, and oral ingestion, said Public Citizen.
“Our petition is based on clear postmarketing evidence that refutes industry propaganda claiming that Botox and related drugs are ‘always safe’ and that no ‘definitive’ cases of botulism have occurred with recommended doses,” Azza AbuDagga, PhD, health services researcher at Public Citizen’s Health Research Group, said in a statement.
Public Citizen said that using data from the FDA’s Adverse Event Reporting System (FAERS), it found 5414 reports of serious outcomes from botulinum toxin products from January 1989 through March 2021. Almost 22% involved cosmetic indications and about 78% involved therapeutic indications.
Of the 5414 reports, 121 (2%) specified botulism as an adverse reaction; 89 involved therapeutic uses of a botulinum toxin products, and 32 involved cosmetic uses. Many of those 121 reports involved doses within the recommended range for the indication, according to Public Citizen.
The group is also asking the FDA to remove what it calls misleading promotional statements in the labeling of Botox and Botox Cosmetic and from the medication guides for those products. The labels state that there have been “no definitive serious adverse event reports of distant spread of toxin effect” with either the cosmetic use or for use in treating chronic migraine, severe underarm sweating, blepharospasm, or strabismus. These statements do not appear in similar labeling in other countries, such as Canada and the United Kingdom, said Public Citizen.
“The FDA needs to implement our two requested actions quickly to warn the public in unambiguous terms about the risk of botulism associated with the use of Botox and related drugs,” Dr. AbuDagga said in the Public Citizen statement. “This will allow health care professionals and patients to make more informed decisions about the benefit-risk profile of these widely used drugs.”
The Public Citizen petition would apply to all seven approved botulinum toxin biological products: abobotulinumtoxinA (Dysport), daxibotulinumtoxinA-lanm (Daxxify), incobotulinumtoxinA (Xeomin), onabotulinumtoxinA (Botox, Botox Cosmetic), prabotulinumtoxinA-xvfs (Jeuveau) and rimabotulinumtoxinB (Myobloc).
An FDA spokesperson said the agency is reviewing the citizen petition, and that generally the agency does not comment on pending petitions. “When we respond to the petition, we will respond directly to the petitioner and post the response in the designated agency docket,” the spokesperson told this news organization. At press time, Botox manufacturer AbbVie had not responded to a request for a comment.
Botulinum toxin is the most-used product for nonsurgical cosmetic procedures, according to the International Society of Aesthetic Plastic Surgery (ISAPS). The ISAPS reported that there were more than 7 million botulinum toxin procedures performed by plastic surgeons worldwide in 2021.
The American Society of Plastic Surgery reported that its members performed 4.4 million Botox procedures in 2020, while the American Society of Dermatologic Surgery (ASDS) said its members performed 2.3 million wrinkle-relaxing procedures in 2019, a 60% increase since 2012.
.
The nonprofit watchdog group successfully petitioned the FDA in 2008 to require a warning for Botox and related products regarding the risk of distant spread of the toxin. In its latest petition to the agency, it says that the injectables need additional warnings about the possibility of iatrogenic botulism with initial and repeated doses and that individuals who contract the condition may need botulinum antitoxin to avert temporary muscle paralysis, hospitalization, and death.
The current warning does not contain any information about the potential need for antitoxin and downplays the need for giving antitoxin in the settings of excessive dosing, accidental injection, and oral ingestion, said Public Citizen.
“Our petition is based on clear postmarketing evidence that refutes industry propaganda claiming that Botox and related drugs are ‘always safe’ and that no ‘definitive’ cases of botulism have occurred with recommended doses,” Azza AbuDagga, PhD, health services researcher at Public Citizen’s Health Research Group, said in a statement.
Public Citizen said that using data from the FDA’s Adverse Event Reporting System (FAERS), it found 5414 reports of serious outcomes from botulinum toxin products from January 1989 through March 2021. Almost 22% involved cosmetic indications and about 78% involved therapeutic indications.
Of the 5414 reports, 121 (2%) specified botulism as an adverse reaction; 89 involved therapeutic uses of a botulinum toxin products, and 32 involved cosmetic uses. Many of those 121 reports involved doses within the recommended range for the indication, according to Public Citizen.
The group is also asking the FDA to remove what it calls misleading promotional statements in the labeling of Botox and Botox Cosmetic and from the medication guides for those products. The labels state that there have been “no definitive serious adverse event reports of distant spread of toxin effect” with either the cosmetic use or for use in treating chronic migraine, severe underarm sweating, blepharospasm, or strabismus. These statements do not appear in similar labeling in other countries, such as Canada and the United Kingdom, said Public Citizen.
“The FDA needs to implement our two requested actions quickly to warn the public in unambiguous terms about the risk of botulism associated with the use of Botox and related drugs,” Dr. AbuDagga said in the Public Citizen statement. “This will allow health care professionals and patients to make more informed decisions about the benefit-risk profile of these widely used drugs.”
The Public Citizen petition would apply to all seven approved botulinum toxin biological products: abobotulinumtoxinA (Dysport), daxibotulinumtoxinA-lanm (Daxxify), incobotulinumtoxinA (Xeomin), onabotulinumtoxinA (Botox, Botox Cosmetic), prabotulinumtoxinA-xvfs (Jeuveau) and rimabotulinumtoxinB (Myobloc).
An FDA spokesperson said the agency is reviewing the citizen petition, and that generally the agency does not comment on pending petitions. “When we respond to the petition, we will respond directly to the petitioner and post the response in the designated agency docket,” the spokesperson told this news organization. At press time, Botox manufacturer AbbVie had not responded to a request for a comment.
Botulinum toxin is the most-used product for nonsurgical cosmetic procedures, according to the International Society of Aesthetic Plastic Surgery (ISAPS). The ISAPS reported that there were more than 7 million botulinum toxin procedures performed by plastic surgeons worldwide in 2021.
The American Society of Plastic Surgery reported that its members performed 4.4 million Botox procedures in 2020, while the American Society of Dermatologic Surgery (ASDS) said its members performed 2.3 million wrinkle-relaxing procedures in 2019, a 60% increase since 2012.
FDA Issues Warning About Counterfeit Ozempic
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Clinicians and patients are advised to check the product packages they have received and not to use those labeled with lot number NAR0074 and serial number 430834149057. Some of these counterfeit products may still be available for purchase, the FDA said in a statement.
Together with Ozempic manufacturer Novo Nordisk, the FDA is investigating “thousands of units” of the 1-mg injection product. Information is not yet available regarding the drugs’ identity, quality, or safety. However, the pen needles have been confirmed as fake — thereby raising the potential risk for infection — as have the pen labels, accompanying health care professional and patient label information, and carton.
“FDA takes reports of possible counterfeit products seriously and works closely with other federal agencies and the private sector to help protect the nation’s drug supply. FDA’s investigation is ongoing, and the agency is working with Novo Nordisk to identify, investigate, and remove further suspected counterfeit semaglutide injectable products found in the US,” the statement says.
Patients are advised to only obtain Ozempic with a valid prescription through state-licensed pharmacies and to check the product before using for any signs of counterfeiting. There are several differences between the genuine and counterfeit products in the way the pen needle is packaged. The most obvious is that the paper tab covering the fake needle says “Novofine®” whereas the genuine one says “Novofine® Plus.”
There have been at least five adverse events reported from this lot; none were serious and all were consistent with gastrointestinal issues known to occur with the genuine product.
Counterfeit products should be reported to the FDA ‘s consumer complaint coordinator or to the criminal activity division.
A version of this article first appeared on Medscape.com.
Roflumilast foam gets nod as new option for seborrheic dermatitis
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
FDA approves first 2 gene-editing therapies for sickle cell
These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.
The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio).
“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.
“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.
Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises.
Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.
Exa-cel
Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production.
The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.
The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion.
The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.
The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia.
Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.
While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.
Lovo-cel
Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells.
Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA
This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events.
Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion.
The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.
The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk.
Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”
Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
A version of this article appeared on Medscape.com.
These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.
The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio).
“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.
“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.
Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises.
Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.
Exa-cel
Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production.
The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.
The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion.
The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.
The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia.
Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.
While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.
Lovo-cel
Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells.
Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA
This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events.
Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion.
The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.
The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk.
Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”
Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
A version of this article appeared on Medscape.com.
These “milestone treatments” mark the first cell-based gene therapies for this debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States.
The two therapies are exagamglogene autotemcel, or exa-cel (Casgevy; Vertex Pharmaceuticals and Crispr Therapeutics), and lovotibeglogene autotemcel, or lovo-cel (Lyfgenia; bluebird bio).
“The approval of the first gene therapies for [sickle cell disease] represents a tremendous step forward for the [sickle cell] community, which has been historically overlooked and underfunded,” said Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, in a statement from the American Society of Hematology, following the approval.
“We are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease, by approving two cell-based gene therapies today,” Nicole Verdun, MD, of the FDA’s Center for Biologics Evaluation and Research, added in an agency press release.
Sickle cell disease involves a mutation in hemoglobin, a protein in red blood cells that provides oxygen to tissues. The mutation leads red blood cells to develop a crescent or sickle shape, which can restrict blood flow and cause severe pain and organ damage, known as vaso-occlusive events or crises.
Treatment options prior to these approvals primarily included red blood transfusions and hydroxyurea alongside pain management. The only potential curative option has been allogeneic hematopoietic stem cell transplantation, but that comes with significant risks and most patients don’t have an appropriate donor.
Exa-cel
Exa-cel uses CRISPR gene-editing technology. Before the infusion, patients undergo myeloablative conditioning, which removes cells from the bone marrow. These cells are genetically modified to produce fetal hemoglobin. Patients then receive an infusion of the edited cells, which can help restore normal hemoglobin production.
The FDA approval was based on data from the pivotal CLIMB SCD-121 trial. In an October advisory committee meeting, the FDA highlighted trial data demonstrating that 29 of 31 patients reached the trial’s primary endpoint: freedom from severe vaso-occlusive crises over a 12-month period. In addition, 28 of these patients remained free of vaso-occlusive crises for almost 2 years.
The committee noted that one of the 31 patients died about 9 months after receiving an exa-cel infusion.
The cell-based gene therapy also increased both fetal and total hemoglobin, with total hemoglobin levels increasing to > 11 g/dL by month 3 and remaining at that level afterward. No patients experienced graft failure or rejection.
The most common side effects included low platelets and white blood cell counts, mouth sores, nausea, musculoskeletal pain, vomiting, and febrile neutropenia.
Exa-cel could “provide a one-time functional cure” for patients with severe sickle cell disease, according to Franco Locatelli, MD, of Sapienza University of Rome, who presented initial findings last year.
While the current approval is for patients with infusion-dependent sickle cell disease, exa-cel is also being evaluated in patients with another blood disorder, beta-thalassemia.
Lovo-cel
Lovo-cel, a cell-based gene therapy, uses a different technology — a lentiviral vector, or gene delivery vehicle — that can also genetically modify a patient’s blood stem cells.
Like exa-cel, lovo-cel is a one-time, single-dose infusion that contains the patient’s modified cells. Before the infusion, patients undergo myeloablative conditioning. The patient’s stem cells are then genetically modified to allow them to produce the most common form of hemoglobin, HbA
This approval was based on data from a single-arm, 24-month study in patients aged 12-50 years who had sickle cell disease and a history of vaso-occlusive events.
Overall, 88% of patients (28 of 32) achieved complete resolution of vaso-occlusive events 6-18 months after the infusion.
The most common side effects included stomatitis; febrile neutropenia; and low platelet, white blood cell, and red blood cell counts.
The FDA noted that hematologic cancer has occurred in patients treated with lovo-cel, and the label includes a black-box warning about the risk.
Dr. Brodsky noted, however, that “while these new gene therapies are potentially life-changing for individuals living with [sickle cell disease], they must be accessible to be effective.”
Access is a potential concern. Exa-cel and lovo-cel could cost about $2 million.
A version of this article appeared on Medscape.com.
FDA greenlights iptacopan to treat paroxysmal nocturnal hemoglobinuria
Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.
“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.
Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.
The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.
APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).
The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.
In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.
In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.
“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.
A version of this article appeared on Medscape.com.
Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.
“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.
Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.
The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.
APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).
The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.
In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.
In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.
“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.
A version of this article appeared on Medscape.com.
Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.
“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.
Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.
The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.
APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).
The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.
In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.
In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.
“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.
A version of this article appeared on Medscape.com.
FDA mandates five changes to iPLEDGE program for isotretinoin
In a letter dated Nov. 30, 2023, the .
The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.
The five changes include the following:
- Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
- Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
- Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
- Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
- Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.
Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.
He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.
Dr. Barbieri reported personal fees from Dexcel Pharma.
In a letter dated Nov. 30, 2023, the .
The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.
The five changes include the following:
- Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
- Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
- Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
- Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
- Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.
Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.
He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.
Dr. Barbieri reported personal fees from Dexcel Pharma.
In a letter dated Nov. 30, 2023, the .
The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.
The five changes include the following:
- Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
- Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
- Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
- Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
- Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.
Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.
He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.
Dr. Barbieri reported personal fees from Dexcel Pharma.
FDA approves pirtobrutinib for previously treated CLL/SLL
The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.
Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.
Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.
“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release.
Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.
Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
A version of this article first appeared on Medscape.com.
The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.
Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.
Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.
“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release.
Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.
Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
A version of this article first appeared on Medscape.com.
The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.
Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.
Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.
“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release.
Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.
Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
A version of this article first appeared on Medscape.com.
FDA warns of potentially lethal reaction to seizure meds
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.
Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).
Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.
In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.
As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.
The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).
In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.
DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.
Label updates
As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.
“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.
They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.
DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.
DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.
Adverse reactions with these medications should be reported to the FDA’s MedWatch program.
A version of this article appeared on Medscape.com.
FDA OKs new agent to block chemotherapy-induced neutropenia
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.
The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.
The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.
The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.
During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.
The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.
The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.
A version of this article first appeared on Medscape.com.
FDA investigates secondary cancers from CAR T-cell therapies
Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.
Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.
Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.
Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).
“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.
Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A version of this article first appeared on Medscape.com.
Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.
Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.
Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.
Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).
“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.
Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A version of this article first appeared on Medscape.com.
Secondary cancers are a known risk for this class of immunotherapies, known as B-cell maturation antigen (BCMA)–directed or CD19-directed autologous CAR T-cell therapies, and are included in the prescribing information for these drugs. However, the FDA has received 19 reports of secondary cancers, including CAR-positive lymphoma, since 2017, when the first CAR T-cell treatments were approved, according to Endpoints News.
Most of these reports came from the FDA’s postmarketing adverse event system and others from clinical trial data.
Although the overall benefits of these products continue to outweigh their potential risks, “FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the agency said in a press release.
Currently approved products in this class include idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus), and axicabtagene ciloleucel (Yescarta).
“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA added.
Suspected adverse events, including T-cell cancers, should be reported by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
A version of this article first appeared on Medscape.com.