FDA/CDC

Two Food and Drug Administration (FDA) advisory panels are urging the agency to eliminate the risk management program for the antipsychotic drug clozapine, saying that restrictions are limiting access to a life-changing and life-saving medication for people with schizophrenia.

Members of the Drug Safety and Risk Management and Psychopharmacologic Drugs advisory committees held a joint meeting on November 19 to address whether frequently revised restrictions that have been in place since clozapine was introduced in 1989 should be changed again. Clozapine — the only FDA-approved drug for treatment-resistant schizophrenia — can cause severe neutropenia, so is subject to a Risk Evaluation and Management Strategy (REMS).

Calling the current rules overly burdensome, a majority of committee members voted against continuing a requirement that pharmacies and physicians must provide documentation of a patient’s absolute neutrophil count (ANC) results through the REMS. Monitoring should continue, as directed in the labeling, said the panel.

Panelists also voted overwhelmingly that it is not necessary to mandate physician education about clozapine’s risk of neutropenia and the need for ANC monitoring.

The panel did not vote, however, on whether the REMS should be eliminated altogether. The FDA did not pose that as a voting question for the panels’ consideration.

Following intense lobbying by the American Psychiatric Association (APA), the National Alliance on Mental Illness, and others, the FDA announced in 2022 that the agency would exercise “enforcement discretion” by allowing prescribers and pharmacists to skirt the clozapine REMS rules. But the agency doesn’t know whether the program is meeting its goals, said Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research.

Among other things, the REMS requires that physicians and pharmacists be certified to prescribe and dispense the drug, that patients be enrolled, and that patient status forms be submitted monthly, showing ANC levels and appropriateness of continuing treatment. 

At the meeting, FDA officials said that 148,000 outpatient clozapine prescriptions were written in 2023. But an estimated 814,000–1.2 million Americans have treatment-resistant schizophrenia, the main indication for clozapine.

“We know the drug is being underutilized,” said Farchione, adding that the agency wants to ensure that physicians and pharmacists “can use the drug, use it safely and help the patients who need it.” 

 

REMS a ‘Hindrance’

As reported by this news organization, research presented earlier this year at the APA annual meeting showed that the risk of moderate and severe neutropenia is low to minimal in people taking clozapine for treatment-resistant schizophrenia. Those findings prompted the study’s investigators to suggest clozapine REMS should be reconsidered.

In the November 19th committee meeting, many panelists said that clozapine was no more dangerous than many antipsychotics and that the administrative requirements were preventing clinicians from prescribing.

“I have fantasized for years about abolishing the clozapine REMS,” said Jacob S. Ballon, MD, MPH, a temporary panel member and associate professor of psychiatry at Stanford University in California.

Panelists Jess Fiedorowicz, MD, PhD, professor and senior research chair in adult psychiatry at the University of Ottawa, Canada; Megan J. Ehret, PharmD, MS, a panelist and professor at the University of Maryland School of Pharmacy, Baltimore; and Rajesh Narendran, MD, a professor in radiology and psychiatry at the University of Pittsburgh School of Medicine in Pennsylvania, agreed.

“I strongly feel that the REMS at this point is just a hindrance,” Narendran said. “I think you should get rid of the REMS.”

However, panelist Walter Dunn, MD, PhD, staff psychiatrist at the VA Greater Los Angeles Healthcare System, cautioned that modifying or eliminating the REMS might not necessarily increase prescribers. If monitoring ANC levels is still recommended in labeling, clinicians will still regard it as the standard of care, said Dunn. And “there are a whole host of other issues associated with clozapine,” that he said were “more concerning.” 

Many patients are accessing clozapine without going through the REMS, which is also of concern to the FDA and drug manufacturers. 

“We estimate about 42,000 patients are not participating in the REMS, said James Shamp, VP of data intelligence and program analytics at United BioSource, a company that supports drug makers.

Leah Hart, PharmD, a risk management analyst with the FDA, told the panel that the agency estimates that 25%-35% of patients taking clozapine may not be participating in the REMS. 

“Today, prescribers, pharmacies, and patients do not have to participate in the REMS in order patients to obtain clozapine,” Hart said.

 

Public Testimony Sways Panel

But psychiatrists, pharmacists, families, and patients who testified during the 90-minute open portion of the meeting disagreed with that assessment, saying the REMS program had a devastatingly chilling effect on clozapine access.

Patty Taggart of Las Vegas said her daughter had nine suicide attempts over the past 14 years, while having tried eight different antipsychotics. In August, after the most-recent attempt, Taggart begged the psychiatrist to prescribe clozapine to her daughter. The clinician refused, citing the REMS. After her daughter’s discharge, Taggart said she found another provider who would prescribe the medication.

Lisa Castellanos said her son Daniel had been treated with a variety of antipsychotics but denied clozapine until he was arrested in 2012 for assault during a psychotic break. The state used the medication to improve Daniel’s mental state so he could stand trial. But when he went to jail after accepting a plea deal, the prison stopped the clozapine. Daniel has since deteriorated and was recently ruled ineligible for parole.

Patients and families also described being rejected at pharmacies — most of which, despite the FDA’s supposed “enforcement discretion” continue to rigorously follow REMS requirements. 

Many panelists said they were moved by patients and family testimony. A dozen or more members of the public were wearing black t-shirts with white writing that declared: “Clozapine is the safest antipsychotic in the world.” 

 

‘Blood-for-Drug Program’

Brian Barnett, MD, director of the psychiatric treatment-resistance program at the Cleveland Clinic in Ohio, said during the public portion of the meeting that “many pharmacies simply refuse to dispense clozapine likely because of the administrative burden and lack of financial incentives.” 

Others want faxed lab results even when the results have been filed electronically, he said. “One of the most dangerous features of the current REMS system is its inflexibility, driven by the so-called ‘no blood, no drug’ ethos which has been baked into the minds of America’s pharmacists.”

“This is a blood-for-drug program,” agreed Rachel Strieff of Tempe, Arizona, who noted that her advocacy group, Angry Moms, and others had submitted 4,000 signatures calling for the end of the REMS. “The largest category of patients harmed by the clozapine REMS have never taken a single dose,” she said, noting that millions of eligible individuals are not getting the drug.

Panel chair James Floyd, MD, professor of medicine at the University of Washington, Seattle, said the public testimony was “very moving.” Families and patients had described “the intensity of suffering that people go through prior to getting to clozapine,” he added.

“We have to listen to that,” said Floyd.


“I want you to know that we hear you,” said Farchione. “We’re here today because of you and your loved ones. And your stories are important, and your experience is important, and what you’ve shared today will have an impact on regulatory decision making.”

While the FDA typically follows its panels’ advice, it’s unclear if the agency will do so for clozapine REMS or when it will release its final decision.

A version of this article appeared on Medscape.com.

Two Food and Drug Administration (FDA) advisory panels are urging the agency to eliminate the risk management program for the antipsychotic drug clozapine, saying that restrictions are limiting access to a life-changing and life-saving medication for people with schizophrenia.

Members of the Drug Safety and Risk Management and Psychopharmacologic Drugs advisory committees held a joint meeting on November 19 to address whether frequently revised restrictions that have been in place since clozapine was introduced in 1989 should be changed again. Clozapine — the only FDA-approved drug for treatment-resistant schizophrenia — can cause severe neutropenia, so is subject to a Risk Evaluation and Management Strategy (REMS).

Calling the current rules overly burdensome, a majority of committee members voted against continuing a requirement that pharmacies and physicians must provide documentation of a patient’s absolute neutrophil count (ANC) results through the REMS. Monitoring should continue, as directed in the labeling, said the panel.

Panelists also voted overwhelmingly that it is not necessary to mandate physician education about clozapine’s risk of neutropenia and the need for ANC monitoring.

The panel did not vote, however, on whether the REMS should be eliminated altogether. The FDA did not pose that as a voting question for the panels’ consideration.

Following intense lobbying by the American Psychiatric Association (APA), the National Alliance on Mental Illness, and others, the FDA announced in 2022 that the agency would exercise “enforcement discretion” by allowing prescribers and pharmacists to skirt the clozapine REMS rules. But the agency doesn’t know whether the program is meeting its goals, said Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research.

Among other things, the REMS requires that physicians and pharmacists be certified to prescribe and dispense the drug, that patients be enrolled, and that patient status forms be submitted monthly, showing ANC levels and appropriateness of continuing treatment. 

At the meeting, FDA officials said that 148,000 outpatient clozapine prescriptions were written in 2023. But an estimated 814,000–1.2 million Americans have treatment-resistant schizophrenia, the main indication for clozapine.

“We know the drug is being underutilized,” said Farchione, adding that the agency wants to ensure that physicians and pharmacists “can use the drug, use it safely and help the patients who need it.” 

 

REMS a ‘Hindrance’

As reported by this news organization, research presented earlier this year at the APA annual meeting showed that the risk of moderate and severe neutropenia is low to minimal in people taking clozapine for treatment-resistant schizophrenia. Those findings prompted the study’s investigators to suggest clozapine REMS should be reconsidered.

In the November 19th committee meeting, many panelists said that clozapine was no more dangerous than many antipsychotics and that the administrative requirements were preventing clinicians from prescribing.

“I have fantasized for years about abolishing the clozapine REMS,” said Jacob S. Ballon, MD, MPH, a temporary panel member and associate professor of psychiatry at Stanford University in California.

Panelists Jess Fiedorowicz, MD, PhD, professor and senior research chair in adult psychiatry at the University of Ottawa, Canada; Megan J. Ehret, PharmD, MS, a panelist and professor at the University of Maryland School of Pharmacy, Baltimore; and Rajesh Narendran, MD, a professor in radiology and psychiatry at the University of Pittsburgh School of Medicine in Pennsylvania, agreed.

“I strongly feel that the REMS at this point is just a hindrance,” Narendran said. “I think you should get rid of the REMS.”

However, panelist Walter Dunn, MD, PhD, staff psychiatrist at the VA Greater Los Angeles Healthcare System, cautioned that modifying or eliminating the REMS might not necessarily increase prescribers. If monitoring ANC levels is still recommended in labeling, clinicians will still regard it as the standard of care, said Dunn. And “there are a whole host of other issues associated with clozapine,” that he said were “more concerning.” 

Many patients are accessing clozapine without going through the REMS, which is also of concern to the FDA and drug manufacturers. 

“We estimate about 42,000 patients are not participating in the REMS, said James Shamp, VP of data intelligence and program analytics at United BioSource, a company that supports drug makers.

Leah Hart, PharmD, a risk management analyst with the FDA, told the panel that the agency estimates that 25%-35% of patients taking clozapine may not be participating in the REMS. 

“Today, prescribers, pharmacies, and patients do not have to participate in the REMS in order patients to obtain clozapine,” Hart said.

 

Public Testimony Sways Panel

But psychiatrists, pharmacists, families, and patients who testified during the 90-minute open portion of the meeting disagreed with that assessment, saying the REMS program had a devastatingly chilling effect on clozapine access.

Patty Taggart of Las Vegas said her daughter had nine suicide attempts over the past 14 years, while having tried eight different antipsychotics. In August, after the most-recent attempt, Taggart begged the psychiatrist to prescribe clozapine to her daughter. The clinician refused, citing the REMS. After her daughter’s discharge, Taggart said she found another provider who would prescribe the medication.

Lisa Castellanos said her son Daniel had been treated with a variety of antipsychotics but denied clozapine until he was arrested in 2012 for assault during a psychotic break. The state used the medication to improve Daniel’s mental state so he could stand trial. But when he went to jail after accepting a plea deal, the prison stopped the clozapine. Daniel has since deteriorated and was recently ruled ineligible for parole.

Patients and families also described being rejected at pharmacies — most of which, despite the FDA’s supposed “enforcement discretion” continue to rigorously follow REMS requirements. 

Many panelists said they were moved by patients and family testimony. A dozen or more members of the public were wearing black t-shirts with white writing that declared: “Clozapine is the safest antipsychotic in the world.” 

 

‘Blood-for-Drug Program’

Brian Barnett, MD, director of the psychiatric treatment-resistance program at the Cleveland Clinic in Ohio, said during the public portion of the meeting that “many pharmacies simply refuse to dispense clozapine likely because of the administrative burden and lack of financial incentives.” 

Others want faxed lab results even when the results have been filed electronically, he said. “One of the most dangerous features of the current REMS system is its inflexibility, driven by the so-called ‘no blood, no drug’ ethos which has been baked into the minds of America’s pharmacists.”

“This is a blood-for-drug program,” agreed Rachel Strieff of Tempe, Arizona, who noted that her advocacy group, Angry Moms, and others had submitted 4,000 signatures calling for the end of the REMS. “The largest category of patients harmed by the clozapine REMS have never taken a single dose,” she said, noting that millions of eligible individuals are not getting the drug.

Panel chair James Floyd, MD, professor of medicine at the University of Washington, Seattle, said the public testimony was “very moving.” Families and patients had described “the intensity of suffering that people go through prior to getting to clozapine,” he added.

“We have to listen to that,” said Floyd.


“I want you to know that we hear you,” said Farchione. “We’re here today because of you and your loved ones. And your stories are important, and your experience is important, and what you’ve shared today will have an impact on regulatory decision making.”

While the FDA typically follows its panels’ advice, it’s unclear if the agency will do so for clozapine REMS or when it will release its final decision.

A version of this article appeared on Medscape.com.

Two Food and Drug Administration (FDA) advisory panels are urging the agency to eliminate the risk management program for the antipsychotic drug clozapine, saying that restrictions are limiting access to a life-changing and life-saving medication for people with schizophrenia.

Members of the Drug Safety and Risk Management and Psychopharmacologic Drugs advisory committees held a joint meeting on November 19 to address whether frequently revised restrictions that have been in place since clozapine was introduced in 1989 should be changed again. Clozapine — the only FDA-approved drug for treatment-resistant schizophrenia — can cause severe neutropenia, so is subject to a Risk Evaluation and Management Strategy (REMS).

Calling the current rules overly burdensome, a majority of committee members voted against continuing a requirement that pharmacies and physicians must provide documentation of a patient’s absolute neutrophil count (ANC) results through the REMS. Monitoring should continue, as directed in the labeling, said the panel.

Panelists also voted overwhelmingly that it is not necessary to mandate physician education about clozapine’s risk of neutropenia and the need for ANC monitoring.

The panel did not vote, however, on whether the REMS should be eliminated altogether. The FDA did not pose that as a voting question for the panels’ consideration.

Following intense lobbying by the American Psychiatric Association (APA), the National Alliance on Mental Illness, and others, the FDA announced in 2022 that the agency would exercise “enforcement discretion” by allowing prescribers and pharmacists to skirt the clozapine REMS rules. But the agency doesn’t know whether the program is meeting its goals, said Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research.

Among other things, the REMS requires that physicians and pharmacists be certified to prescribe and dispense the drug, that patients be enrolled, and that patient status forms be submitted monthly, showing ANC levels and appropriateness of continuing treatment. 

At the meeting, FDA officials said that 148,000 outpatient clozapine prescriptions were written in 2023. But an estimated 814,000–1.2 million Americans have treatment-resistant schizophrenia, the main indication for clozapine.

“We know the drug is being underutilized,” said Farchione, adding that the agency wants to ensure that physicians and pharmacists “can use the drug, use it safely and help the patients who need it.” 

 

REMS a ‘Hindrance’

As reported by this news organization, research presented earlier this year at the APA annual meeting showed that the risk of moderate and severe neutropenia is low to minimal in people taking clozapine for treatment-resistant schizophrenia. Those findings prompted the study’s investigators to suggest clozapine REMS should be reconsidered.

In the November 19th committee meeting, many panelists said that clozapine was no more dangerous than many antipsychotics and that the administrative requirements were preventing clinicians from prescribing.

“I have fantasized for years about abolishing the clozapine REMS,” said Jacob S. Ballon, MD, MPH, a temporary panel member and associate professor of psychiatry at Stanford University in California.

Panelists Jess Fiedorowicz, MD, PhD, professor and senior research chair in adult psychiatry at the University of Ottawa, Canada; Megan J. Ehret, PharmD, MS, a panelist and professor at the University of Maryland School of Pharmacy, Baltimore; and Rajesh Narendran, MD, a professor in radiology and psychiatry at the University of Pittsburgh School of Medicine in Pennsylvania, agreed.

“I strongly feel that the REMS at this point is just a hindrance,” Narendran said. “I think you should get rid of the REMS.”

However, panelist Walter Dunn, MD, PhD, staff psychiatrist at the VA Greater Los Angeles Healthcare System, cautioned that modifying or eliminating the REMS might not necessarily increase prescribers. If monitoring ANC levels is still recommended in labeling, clinicians will still regard it as the standard of care, said Dunn. And “there are a whole host of other issues associated with clozapine,” that he said were “more concerning.” 

Many patients are accessing clozapine without going through the REMS, which is also of concern to the FDA and drug manufacturers. 

“We estimate about 42,000 patients are not participating in the REMS, said James Shamp, VP of data intelligence and program analytics at United BioSource, a company that supports drug makers.

Leah Hart, PharmD, a risk management analyst with the FDA, told the panel that the agency estimates that 25%-35% of patients taking clozapine may not be participating in the REMS. 

“Today, prescribers, pharmacies, and patients do not have to participate in the REMS in order patients to obtain clozapine,” Hart said.

 

Public Testimony Sways Panel

But psychiatrists, pharmacists, families, and patients who testified during the 90-minute open portion of the meeting disagreed with that assessment, saying the REMS program had a devastatingly chilling effect on clozapine access.

Patty Taggart of Las Vegas said her daughter had nine suicide attempts over the past 14 years, while having tried eight different antipsychotics. In August, after the most-recent attempt, Taggart begged the psychiatrist to prescribe clozapine to her daughter. The clinician refused, citing the REMS. After her daughter’s discharge, Taggart said she found another provider who would prescribe the medication.

Lisa Castellanos said her son Daniel had been treated with a variety of antipsychotics but denied clozapine until he was arrested in 2012 for assault during a psychotic break. The state used the medication to improve Daniel’s mental state so he could stand trial. But when he went to jail after accepting a plea deal, the prison stopped the clozapine. Daniel has since deteriorated and was recently ruled ineligible for parole.

Patients and families also described being rejected at pharmacies — most of which, despite the FDA’s supposed “enforcement discretion” continue to rigorously follow REMS requirements. 

Many panelists said they were moved by patients and family testimony. A dozen or more members of the public were wearing black t-shirts with white writing that declared: “Clozapine is the safest antipsychotic in the world.” 

 

‘Blood-for-Drug Program’

Brian Barnett, MD, director of the psychiatric treatment-resistance program at the Cleveland Clinic in Ohio, said during the public portion of the meeting that “many pharmacies simply refuse to dispense clozapine likely because of the administrative burden and lack of financial incentives.” 

Others want faxed lab results even when the results have been filed electronically, he said. “One of the most dangerous features of the current REMS system is its inflexibility, driven by the so-called ‘no blood, no drug’ ethos which has been baked into the minds of America’s pharmacists.”

“This is a blood-for-drug program,” agreed Rachel Strieff of Tempe, Arizona, who noted that her advocacy group, Angry Moms, and others had submitted 4,000 signatures calling for the end of the REMS. “The largest category of patients harmed by the clozapine REMS have never taken a single dose,” she said, noting that millions of eligible individuals are not getting the drug.

Panel chair James Floyd, MD, professor of medicine at the University of Washington, Seattle, said the public testimony was “very moving.” Families and patients had described “the intensity of suffering that people go through prior to getting to clozapine,” he added.

“We have to listen to that,” said Floyd.


“I want you to know that we hear you,” said Farchione. “We’re here today because of you and your loved ones. And your stories are important, and your experience is important, and what you’ve shared today will have an impact on regulatory decision making.”

While the FDA typically follows its panels’ advice, it’s unclear if the agency will do so for clozapine REMS or when it will release its final decision.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved zanidatamab (Ziihera, Jazz Pharmaceuticals) as monotherapy for previously treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC). This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication. 

Zanidatamab binds two separate regions on the HER2 cell surface protein, crosslinking neighboring HER2 proteins, blocking HER2 signaling, and inducing cytotoxic immune responses.

The FDA simultaneously announced that it has also approved VENTANA PATHWAY anti–HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to aid in identifying patients with BTC who may be eligible for treatment with zanidatamab.

 

Zanidatamab Trial Results

The approval of zanidatamab was based on the phase 2b HERIZON-BTC-01 trial— which was open-label, multicenter, and single-arm — involving 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. In this trial, zanidatamab 20 mg/kg was administered every 2 weeks to patients who had received gemcitabine-containing chemotherapy previously but not a HER2-targeted therapy.

The objective response rate was 52%, and the median duration of response was 14.9 months, according to the statement from the FDA.

The life expectancy for advanced BTC treated in the second line with standard chemotherapy is approximately 6-9 months, according to Jazz Pharmaceuticals. 

 

Boxed Warning and Adverse Events

The prescribing information contains a boxed warning for embryo-fetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.

The recommended zanidatamab dose is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until progression or unacceptable toxicity. 

Jazz Pharmaceuticals’ application was granted priority review, breakthrough therapy designation, and orphan drug designation.

An ongoing phase 3 trial, HERIZON-BTC-302, is testing zanidatamab in combination with standard-of-care therapy in the first-line setting for advanced or metastatic HER2-positive BTC. The bispecific antibody is also being developed for HER2-positive advanced/metastatic gastroesophageal adenocarcinoma.

A version of this article appeared on Medscape.com. 

The Food and Drug Administration (FDA) has approved zanidatamab (Ziihera, Jazz Pharmaceuticals) as monotherapy for previously treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC). This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication. 

Zanidatamab binds two separate regions on the HER2 cell surface protein, crosslinking neighboring HER2 proteins, blocking HER2 signaling, and inducing cytotoxic immune responses.

The FDA simultaneously announced that it has also approved VENTANA PATHWAY anti–HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to aid in identifying patients with BTC who may be eligible for treatment with zanidatamab.

 

Zanidatamab Trial Results

The approval of zanidatamab was based on the phase 2b HERIZON-BTC-01 trial— which was open-label, multicenter, and single-arm — involving 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. In this trial, zanidatamab 20 mg/kg was administered every 2 weeks to patients who had received gemcitabine-containing chemotherapy previously but not a HER2-targeted therapy.

The objective response rate was 52%, and the median duration of response was 14.9 months, according to the statement from the FDA.

The life expectancy for advanced BTC treated in the second line with standard chemotherapy is approximately 6-9 months, according to Jazz Pharmaceuticals. 

 

Boxed Warning and Adverse Events

The prescribing information contains a boxed warning for embryo-fetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.

The recommended zanidatamab dose is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until progression or unacceptable toxicity. 

Jazz Pharmaceuticals’ application was granted priority review, breakthrough therapy designation, and orphan drug designation.

An ongoing phase 3 trial, HERIZON-BTC-302, is testing zanidatamab in combination with standard-of-care therapy in the first-line setting for advanced or metastatic HER2-positive BTC. The bispecific antibody is also being developed for HER2-positive advanced/metastatic gastroesophageal adenocarcinoma.

A version of this article appeared on Medscape.com. 

The Food and Drug Administration (FDA) has approved zanidatamab (Ziihera, Jazz Pharmaceuticals) as monotherapy for previously treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC). This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication. 

Zanidatamab binds two separate regions on the HER2 cell surface protein, crosslinking neighboring HER2 proteins, blocking HER2 signaling, and inducing cytotoxic immune responses.

The FDA simultaneously announced that it has also approved VENTANA PATHWAY anti–HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to aid in identifying patients with BTC who may be eligible for treatment with zanidatamab.

 

Zanidatamab Trial Results

The approval of zanidatamab was based on the phase 2b HERIZON-BTC-01 trial— which was open-label, multicenter, and single-arm — involving 62 patients with unresectable or metastatic HER2-positive (IHC3+) BTC. In this trial, zanidatamab 20 mg/kg was administered every 2 weeks to patients who had received gemcitabine-containing chemotherapy previously but not a HER2-targeted therapy.

The objective response rate was 52%, and the median duration of response was 14.9 months, according to the statement from the FDA.

The life expectancy for advanced BTC treated in the second line with standard chemotherapy is approximately 6-9 months, according to Jazz Pharmaceuticals. 

 

Boxed Warning and Adverse Events

The prescribing information contains a boxed warning for embryo-fetal toxicity. The most common adverse reactions reported in at least 20% of patients who received zanidatamab were diarrhea, infusion-related reactions, abdominal pain, and fatigue.

The recommended zanidatamab dose is 20 mg/kg, administered as an intravenous infusion once every 2 weeks until progression or unacceptable toxicity. 

Jazz Pharmaceuticals’ application was granted priority review, breakthrough therapy designation, and orphan drug designation.

An ongoing phase 3 trial, HERIZON-BTC-302, is testing zanidatamab in combination with standard-of-care therapy in the first-line setting for advanced or metastatic HER2-positive BTC. The bispecific antibody is also being developed for HER2-positive advanced/metastatic gastroesophageal adenocarcinoma.

A version of this article appeared on Medscape.com. 

The persistent epidemic of sexually transmitted infections (STIs) in the United States is showing signs of a slowdown in cases of syphilis, gonorrhea, and chlamydia, according to the latest data from the Centers for Disease Control and Prevention (CDC).

More than 2.4 million cases of these three nationally notifiable STIs were reported in the United States in 2023 but represent a 1.8% decrease from 2022, based on a new CDC report, Sexually Transmitted Infections Surveillance, 2023.

The 2023 report indicates a 7.2% decrease in gonorrhea, which accounts for most of the decrease.

Although syphilis cases increased overall, they did so by only 1% compared with double-digit increases in previous years, according to the report. Primary and secondary syphilis decreased by 10%, compared with 2022 overall, with a 13% decrease in cases among gay and bisexual men.

Congenital syphilis rates increased by 3%. However, the 3% increase represents a significant drop from the 30% increases each year in recent years, according to the report.

Chlamydia rates remained essentially stable, with a decrease of less than 1.0% overall. Reported chlamydia rates increased by 1.3% among men and decreased by 1.7% among women.

Despite the declines, overall disparities persist, with higher rates of STIs among gay and bisexual men, as well as American Indian/Alaska Native, Black/African American, and Hispanic/Latino populations, according to the report.

 

CDC Cautiously Optimistic

The CDC is “guardedly optimistic that the new data represent a turning point in terms of syphilis and gonorrhea,” said Bradley Stoner, MD, director of the CDC’s Division of STD Prevention, in an interview.

However, a tremendous amount of work remains to be done, notably in addressing disparities in care, said Stoner.

New techniques for diagnosis and treatment, such as the increased use of doxycycline (doxy PEP) for the prevention of STIs after sex for high-risk populations with a history of STIs, are likely contributing to the overall decrease, Stoner said. Other contributing factors include improved communication and awareness of STI treatment options at the community level in emergency departments, substance use facilities, and syringe use programs.

Although the United States has not yet turned the corner in reducing STIs, “We are at an inflection point in the epidemic after years of increases,” Stoner told this news organization. “The CDC is committed to keeping the momentum going and turning things around.” Although congenital syphilis rates are slowing down, it remains a significant problem with severe outcomes for mothers and infants, he noted.

The message to healthcare providers on the front lines is to increase awareness, screen widely, and provide effective treatments, Stoner emphasized.

Looking ahead, more research is needed to identify the settings in which prevention tools can be best utilized, such as urgent care or other programs, said Stoner. “My hope is that implementation science research will give us some clues.” In addition, better tools for detection and treatment of STIs are always needed, notably better diagnostics for syphilis, which still requires a blood test, although research is underway for more efficient testing.

 

Spotlight on Disparities, Syphilis

“I think these are very nuanced results,” said David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, in an interview. “I am happy, on first pass, to see that STI rates have declined.” However, a closer look reveals that most of the improvements are driven by the 7% drop in gonorrhea, while chlamydia and syphilis rates are relatively stable.

The decreases may reflect that the public is receiving the messaging about the need for screening and safer sex. “Clinicians also have been educated on the need for screening,” Cennimo said. However, “we are still 90% above the [STI] rates from 20 years ago.”

Clinicians also must recognize the disparities in STI rates by race and other demographics, Cennimo said. The current report “is a call to make sure that STI and other medical services are targeted to specific groups as needed and are widely available, especially in under-resourced areas.”

“I am still dismayed by the high syphilis rates, which are also resulting in congenital syphilis,” Cennimo said. “Syphilis in pregnancy is very dangerous, and any case of congenital syphilis is a failure of preventive care and screening; it is a potentially devastating disease.

“We have good treatments for STIs, but we must continue to monitor for resistance,” said Cennimo. “More work is needed to reach high-risk individuals and to provide preventive care and screening.” 

The research was supported by the CDC. Stoner and Cennimo had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

The persistent epidemic of sexually transmitted infections (STIs) in the United States is showing signs of a slowdown in cases of syphilis, gonorrhea, and chlamydia, according to the latest data from the Centers for Disease Control and Prevention (CDC).

More than 2.4 million cases of these three nationally notifiable STIs were reported in the United States in 2023 but represent a 1.8% decrease from 2022, based on a new CDC report, Sexually Transmitted Infections Surveillance, 2023.

The 2023 report indicates a 7.2% decrease in gonorrhea, which accounts for most of the decrease.

Although syphilis cases increased overall, they did so by only 1% compared with double-digit increases in previous years, according to the report. Primary and secondary syphilis decreased by 10%, compared with 2022 overall, with a 13% decrease in cases among gay and bisexual men.

Congenital syphilis rates increased by 3%. However, the 3% increase represents a significant drop from the 30% increases each year in recent years, according to the report.

Chlamydia rates remained essentially stable, with a decrease of less than 1.0% overall. Reported chlamydia rates increased by 1.3% among men and decreased by 1.7% among women.

Despite the declines, overall disparities persist, with higher rates of STIs among gay and bisexual men, as well as American Indian/Alaska Native, Black/African American, and Hispanic/Latino populations, according to the report.

 

CDC Cautiously Optimistic

The CDC is “guardedly optimistic that the new data represent a turning point in terms of syphilis and gonorrhea,” said Bradley Stoner, MD, director of the CDC’s Division of STD Prevention, in an interview.

However, a tremendous amount of work remains to be done, notably in addressing disparities in care, said Stoner.

New techniques for diagnosis and treatment, such as the increased use of doxycycline (doxy PEP) for the prevention of STIs after sex for high-risk populations with a history of STIs, are likely contributing to the overall decrease, Stoner said. Other contributing factors include improved communication and awareness of STI treatment options at the community level in emergency departments, substance use facilities, and syringe use programs.

Although the United States has not yet turned the corner in reducing STIs, “We are at an inflection point in the epidemic after years of increases,” Stoner told this news organization. “The CDC is committed to keeping the momentum going and turning things around.” Although congenital syphilis rates are slowing down, it remains a significant problem with severe outcomes for mothers and infants, he noted.

The message to healthcare providers on the front lines is to increase awareness, screen widely, and provide effective treatments, Stoner emphasized.

Looking ahead, more research is needed to identify the settings in which prevention tools can be best utilized, such as urgent care or other programs, said Stoner. “My hope is that implementation science research will give us some clues.” In addition, better tools for detection and treatment of STIs are always needed, notably better diagnostics for syphilis, which still requires a blood test, although research is underway for more efficient testing.

 

Spotlight on Disparities, Syphilis

“I think these are very nuanced results,” said David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, in an interview. “I am happy, on first pass, to see that STI rates have declined.” However, a closer look reveals that most of the improvements are driven by the 7% drop in gonorrhea, while chlamydia and syphilis rates are relatively stable.

The decreases may reflect that the public is receiving the messaging about the need for screening and safer sex. “Clinicians also have been educated on the need for screening,” Cennimo said. However, “we are still 90% above the [STI] rates from 20 years ago.”

Clinicians also must recognize the disparities in STI rates by race and other demographics, Cennimo said. The current report “is a call to make sure that STI and other medical services are targeted to specific groups as needed and are widely available, especially in under-resourced areas.”

“I am still dismayed by the high syphilis rates, which are also resulting in congenital syphilis,” Cennimo said. “Syphilis in pregnancy is very dangerous, and any case of congenital syphilis is a failure of preventive care and screening; it is a potentially devastating disease.

“We have good treatments for STIs, but we must continue to monitor for resistance,” said Cennimo. “More work is needed to reach high-risk individuals and to provide preventive care and screening.” 

The research was supported by the CDC. Stoner and Cennimo had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

The persistent epidemic of sexually transmitted infections (STIs) in the United States is showing signs of a slowdown in cases of syphilis, gonorrhea, and chlamydia, according to the latest data from the Centers for Disease Control and Prevention (CDC).

More than 2.4 million cases of these three nationally notifiable STIs were reported in the United States in 2023 but represent a 1.8% decrease from 2022, based on a new CDC report, Sexually Transmitted Infections Surveillance, 2023.

The 2023 report indicates a 7.2% decrease in gonorrhea, which accounts for most of the decrease.

Although syphilis cases increased overall, they did so by only 1% compared with double-digit increases in previous years, according to the report. Primary and secondary syphilis decreased by 10%, compared with 2022 overall, with a 13% decrease in cases among gay and bisexual men.

Congenital syphilis rates increased by 3%. However, the 3% increase represents a significant drop from the 30% increases each year in recent years, according to the report.

Chlamydia rates remained essentially stable, with a decrease of less than 1.0% overall. Reported chlamydia rates increased by 1.3% among men and decreased by 1.7% among women.

Despite the declines, overall disparities persist, with higher rates of STIs among gay and bisexual men, as well as American Indian/Alaska Native, Black/African American, and Hispanic/Latino populations, according to the report.

 

CDC Cautiously Optimistic

The CDC is “guardedly optimistic that the new data represent a turning point in terms of syphilis and gonorrhea,” said Bradley Stoner, MD, director of the CDC’s Division of STD Prevention, in an interview.

However, a tremendous amount of work remains to be done, notably in addressing disparities in care, said Stoner.

New techniques for diagnosis and treatment, such as the increased use of doxycycline (doxy PEP) for the prevention of STIs after sex for high-risk populations with a history of STIs, are likely contributing to the overall decrease, Stoner said. Other contributing factors include improved communication and awareness of STI treatment options at the community level in emergency departments, substance use facilities, and syringe use programs.

Although the United States has not yet turned the corner in reducing STIs, “We are at an inflection point in the epidemic after years of increases,” Stoner told this news organization. “The CDC is committed to keeping the momentum going and turning things around.” Although congenital syphilis rates are slowing down, it remains a significant problem with severe outcomes for mothers and infants, he noted.

The message to healthcare providers on the front lines is to increase awareness, screen widely, and provide effective treatments, Stoner emphasized.

Looking ahead, more research is needed to identify the settings in which prevention tools can be best utilized, such as urgent care or other programs, said Stoner. “My hope is that implementation science research will give us some clues.” In addition, better tools for detection and treatment of STIs are always needed, notably better diagnostics for syphilis, which still requires a blood test, although research is underway for more efficient testing.

 

Spotlight on Disparities, Syphilis

“I think these are very nuanced results,” said David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, in an interview. “I am happy, on first pass, to see that STI rates have declined.” However, a closer look reveals that most of the improvements are driven by the 7% drop in gonorrhea, while chlamydia and syphilis rates are relatively stable.

The decreases may reflect that the public is receiving the messaging about the need for screening and safer sex. “Clinicians also have been educated on the need for screening,” Cennimo said. However, “we are still 90% above the [STI] rates from 20 years ago.”

Clinicians also must recognize the disparities in STI rates by race and other demographics, Cennimo said. The current report “is a call to make sure that STI and other medical services are targeted to specific groups as needed and are widely available, especially in under-resourced areas.”

“I am still dismayed by the high syphilis rates, which are also resulting in congenital syphilis,” Cennimo said. “Syphilis in pregnancy is very dangerous, and any case of congenital syphilis is a failure of preventive care and screening; it is a potentially devastating disease.

“We have good treatments for STIs, but we must continue to monitor for resistance,” said Cennimo. “More work is needed to reach high-risk individuals and to provide preventive care and screening.” 

The research was supported by the CDC. Stoner and Cennimo had no financial conflicts to disclose.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved bimekizumab, a humanized interleukin (IL)-17A and IL-17F antagonist, for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).

Approval was based on results from two phase 3 studies, BE HEARD I and BE HEARD II, which found that bimekizumab improved the signs and symptoms of disease compared with placebo at week 16 and were sustained to week 48, according to a press release from UCB, the drug’s manufacturer. In both trials, a higher proportion of patients treated with bimekizumab achieved Hidradenitis Suppurativa Clinical Response (HiSCR) scores of 50 and 75 compared with those who received placebo.

The company noted that bimekizumab (Bimzelx) is the first and only approved medicine designed to selectively inhibit IL-17F in addition to IL-17A. According to the prescribing information, the recommended dosing for patients with HS is 320 mg administered by subcutaneous injection at week 0, 2, 4, 6, 8, 10, 12, 14, and 16, then every 4 weeks thereafter.

“The approval of bimekizumab for moderate-to-severe HS is tremendous news for people living with HS” and the clinicians who care for them, Jennifer L. Hsiao, MD, director of the HS clinic at the University of Southern California, Los Angeles, told this news organization.

“It is exciting that we already have two-year trial data for bimekizumab in HS and can see that bimekizumab raises the bar in terms of depth and durability of response that we can expect to see in our patients,” she added. “Given the limited treatment options for HS at this time, the addition of bimekizumab to our treatment armamentarium is a huge step forward for the HS community.”

This development marks the fifth approved indication for bimekizumab since it was first approved in October 2023 for the treatment of moderate to severe plaque psoriasis, followed by approvals for active psoriatic arthritis, nonradiographic axial spondyloarthritis, and active ankylosing spondylitis in September 2024. 

According to the prescribing information, certain adverse reactions have been observed with bimekizumab, including suicidal ideation and behavior, infections, liver biochemical abnormalities, and inflammatory bowel disease. A pregnancy exposure registry has been established that monitors pregnancy outcomes in women exposed to bimekizumab. For information, clinicians or patients can contact the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases Study at 1-877-311- 8972 or visit MotherToBaby Pregnancy Studies.

Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, Sanofi, and UCB; a speaker for AbbVie, Galderma, Novartis, Sanofi Regeneron, and UCB; and an investigator for Amgen, Boehringer Ingelheim, and Incyte.

 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved bimekizumab, a humanized interleukin (IL)-17A and IL-17F antagonist, for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).

Approval was based on results from two phase 3 studies, BE HEARD I and BE HEARD II, which found that bimekizumab improved the signs and symptoms of disease compared with placebo at week 16 and were sustained to week 48, according to a press release from UCB, the drug’s manufacturer. In both trials, a higher proportion of patients treated with bimekizumab achieved Hidradenitis Suppurativa Clinical Response (HiSCR) scores of 50 and 75 compared with those who received placebo.

The company noted that bimekizumab (Bimzelx) is the first and only approved medicine designed to selectively inhibit IL-17F in addition to IL-17A. According to the prescribing information, the recommended dosing for patients with HS is 320 mg administered by subcutaneous injection at week 0, 2, 4, 6, 8, 10, 12, 14, and 16, then every 4 weeks thereafter.

“The approval of bimekizumab for moderate-to-severe HS is tremendous news for people living with HS” and the clinicians who care for them, Jennifer L. Hsiao, MD, director of the HS clinic at the University of Southern California, Los Angeles, told this news organization.

“It is exciting that we already have two-year trial data for bimekizumab in HS and can see that bimekizumab raises the bar in terms of depth and durability of response that we can expect to see in our patients,” she added. “Given the limited treatment options for HS at this time, the addition of bimekizumab to our treatment armamentarium is a huge step forward for the HS community.”

This development marks the fifth approved indication for bimekizumab since it was first approved in October 2023 for the treatment of moderate to severe plaque psoriasis, followed by approvals for active psoriatic arthritis, nonradiographic axial spondyloarthritis, and active ankylosing spondylitis in September 2024. 

According to the prescribing information, certain adverse reactions have been observed with bimekizumab, including suicidal ideation and behavior, infections, liver biochemical abnormalities, and inflammatory bowel disease. A pregnancy exposure registry has been established that monitors pregnancy outcomes in women exposed to bimekizumab. For information, clinicians or patients can contact the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases Study at 1-877-311- 8972 or visit MotherToBaby Pregnancy Studies.

Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, Sanofi, and UCB; a speaker for AbbVie, Galderma, Novartis, Sanofi Regeneron, and UCB; and an investigator for Amgen, Boehringer Ingelheim, and Incyte.

 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved bimekizumab, a humanized interleukin (IL)-17A and IL-17F antagonist, for the treatment of adults with moderate to severe hidradenitis suppurativa (HS).

Approval was based on results from two phase 3 studies, BE HEARD I and BE HEARD II, which found that bimekizumab improved the signs and symptoms of disease compared with placebo at week 16 and were sustained to week 48, according to a press release from UCB, the drug’s manufacturer. In both trials, a higher proportion of patients treated with bimekizumab achieved Hidradenitis Suppurativa Clinical Response (HiSCR) scores of 50 and 75 compared with those who received placebo.

The company noted that bimekizumab (Bimzelx) is the first and only approved medicine designed to selectively inhibit IL-17F in addition to IL-17A. According to the prescribing information, the recommended dosing for patients with HS is 320 mg administered by subcutaneous injection at week 0, 2, 4, 6, 8, 10, 12, 14, and 16, then every 4 weeks thereafter.

“The approval of bimekizumab for moderate-to-severe HS is tremendous news for people living with HS” and the clinicians who care for them, Jennifer L. Hsiao, MD, director of the HS clinic at the University of Southern California, Los Angeles, told this news organization.

“It is exciting that we already have two-year trial data for bimekizumab in HS and can see that bimekizumab raises the bar in terms of depth and durability of response that we can expect to see in our patients,” she added. “Given the limited treatment options for HS at this time, the addition of bimekizumab to our treatment armamentarium is a huge step forward for the HS community.”

This development marks the fifth approved indication for bimekizumab since it was first approved in October 2023 for the treatment of moderate to severe plaque psoriasis, followed by approvals for active psoriatic arthritis, nonradiographic axial spondyloarthritis, and active ankylosing spondylitis in September 2024. 

According to the prescribing information, certain adverse reactions have been observed with bimekizumab, including suicidal ideation and behavior, infections, liver biochemical abnormalities, and inflammatory bowel disease. A pregnancy exposure registry has been established that monitors pregnancy outcomes in women exposed to bimekizumab. For information, clinicians or patients can contact the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases Study at 1-877-311- 8972 or visit MotherToBaby Pregnancy Studies.

Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, Sanofi, and UCB; a speaker for AbbVie, Galderma, Novartis, Sanofi Regeneron, and UCB; and an investigator for Amgen, Boehringer Ingelheim, and Incyte.

 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted fast-track approval for a groundbreaking gene therapy indicated for a rare genetic disorder called aromatic L-amino acid decarboxylase (AADC) deficiency. The gene therapy, marketed under the brand name Kebilidi, is the first in the United States to be injected directly into the brain. It is approved for children with fully developed skulls and for adults.

AADC is an enzyme that helps the body make dopamine. AADC deficiency affects patients’ physical, mental, and behavioral health from infancy, leading to severe disabilities and shorter lifespan. Children with AADC may also experience painful seizure-like episodes called oculogyric crises. 

Kebilidi (generic name: eladocagene exuparvovec) is injected into a specific area of the brain where it boosts AADC, restoring dopamine production and gradually improving movement-related symptoms. This surgery is to be performed only by brain surgeons in specialized centers.

The FDA approval was based on the therapy’s safety and effectiveness as shown in an ongoing clinical trial involving 13 children diagnosed with AADC deficiency. According to PTC Therapeutics, the maker of Kebilidi, long-term follow-up studies of the participants are still needed, and additional proof of the therapy’s benefits are required for full FDA approval.

Common side effects of Kebilidi therapy may include involuntary movements (dyskinesia), anemia, fever, low blood pressure, excessive salivation, problems sleeping, low blood levels of certain minerals, and complications after the injection, including breathing or heart problems. The surgical procedure for injecting Kebilidi also carries certain risks, such as cerebrospinal fluid leaks, bleeding in the brain, inflammation, strokes, and infections. 

 

A version of this article appeared on WebMD.com.

The US Food and Drug Administration (FDA) has granted fast-track approval for a groundbreaking gene therapy indicated for a rare genetic disorder called aromatic L-amino acid decarboxylase (AADC) deficiency. The gene therapy, marketed under the brand name Kebilidi, is the first in the United States to be injected directly into the brain. It is approved for children with fully developed skulls and for adults.

AADC is an enzyme that helps the body make dopamine. AADC deficiency affects patients’ physical, mental, and behavioral health from infancy, leading to severe disabilities and shorter lifespan. Children with AADC may also experience painful seizure-like episodes called oculogyric crises. 

Kebilidi (generic name: eladocagene exuparvovec) is injected into a specific area of the brain where it boosts AADC, restoring dopamine production and gradually improving movement-related symptoms. This surgery is to be performed only by brain surgeons in specialized centers.

The FDA approval was based on the therapy’s safety and effectiveness as shown in an ongoing clinical trial involving 13 children diagnosed with AADC deficiency. According to PTC Therapeutics, the maker of Kebilidi, long-term follow-up studies of the participants are still needed, and additional proof of the therapy’s benefits are required for full FDA approval.

Common side effects of Kebilidi therapy may include involuntary movements (dyskinesia), anemia, fever, low blood pressure, excessive salivation, problems sleeping, low blood levels of certain minerals, and complications after the injection, including breathing or heart problems. The surgical procedure for injecting Kebilidi also carries certain risks, such as cerebrospinal fluid leaks, bleeding in the brain, inflammation, strokes, and infections. 

 

A version of this article appeared on WebMD.com.

The US Food and Drug Administration (FDA) has granted fast-track approval for a groundbreaking gene therapy indicated for a rare genetic disorder called aromatic L-amino acid decarboxylase (AADC) deficiency. The gene therapy, marketed under the brand name Kebilidi, is the first in the United States to be injected directly into the brain. It is approved for children with fully developed skulls and for adults.

AADC is an enzyme that helps the body make dopamine. AADC deficiency affects patients’ physical, mental, and behavioral health from infancy, leading to severe disabilities and shorter lifespan. Children with AADC may also experience painful seizure-like episodes called oculogyric crises. 

Kebilidi (generic name: eladocagene exuparvovec) is injected into a specific area of the brain where it boosts AADC, restoring dopamine production and gradually improving movement-related symptoms. This surgery is to be performed only by brain surgeons in specialized centers.

The FDA approval was based on the therapy’s safety and effectiveness as shown in an ongoing clinical trial involving 13 children diagnosed with AADC deficiency. According to PTC Therapeutics, the maker of Kebilidi, long-term follow-up studies of the participants are still needed, and additional proof of the therapy’s benefits are required for full FDA approval.

Common side effects of Kebilidi therapy may include involuntary movements (dyskinesia), anemia, fever, low blood pressure, excessive salivation, problems sleeping, low blood levels of certain minerals, and complications after the injection, including breathing or heart problems. The surgical procedure for injecting Kebilidi also carries certain risks, such as cerebrospinal fluid leaks, bleeding in the brain, inflammation, strokes, and infections. 

 

A version of this article appeared on WebMD.com.

The Food and Drug Administration has approved revumenib (Revuforj — Syndax Pharmaceuticals) for relapsed or refractory acute leukemia with a KMT2A gene translocation in adult and pediatric patients 1 year or older.

The approval makes the oral small-molecule menin inhibitor the first pharmaceutical to carry the indication. It blocks the binding of menin to mutated KMT2A fusion proteins, tamping down the process that leads to the disease.

Although a relatively uncommon form of leukemia, KMT2A rearrangements are a major driver of acute leukemia in infants.

Approval was based on a single-arm of the open-label AUGMENT-101 trial with 104 adult and pediatric patients with the mutation. Pediatric patients were at least 30 days old.

The rate of complete remission (CR) plus CR with partial hematologic recovery was 21.2% (22 patients) with a median duration of 6.4 months. The median time to remission was 1.9 months.

Eighty-three patients required blood cell and/or platelet transfusions at baseline; 12 (14%) did not need transfusions for 56 days afterward. Of the 21 who were transfusion free at baseline, 10 (48%) remained so over the same period.

The most common adverse reactions in 20% or more of patients were hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolonged, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.

The recommended dose varies by weight and concomitant use of strong CYP3A4 inhibitors. Because of an anticipated delay in commercial availability, the lowest strength dose of revumenib will be available through an expanded access program for patients who weigh < 40 kg.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved revumenib (Revuforj — Syndax Pharmaceuticals) for relapsed or refractory acute leukemia with a KMT2A gene translocation in adult and pediatric patients 1 year or older.

The approval makes the oral small-molecule menin inhibitor the first pharmaceutical to carry the indication. It blocks the binding of menin to mutated KMT2A fusion proteins, tamping down the process that leads to the disease.

Although a relatively uncommon form of leukemia, KMT2A rearrangements are a major driver of acute leukemia in infants.

Approval was based on a single-arm of the open-label AUGMENT-101 trial with 104 adult and pediatric patients with the mutation. Pediatric patients were at least 30 days old.

The rate of complete remission (CR) plus CR with partial hematologic recovery was 21.2% (22 patients) with a median duration of 6.4 months. The median time to remission was 1.9 months.

Eighty-three patients required blood cell and/or platelet transfusions at baseline; 12 (14%) did not need transfusions for 56 days afterward. Of the 21 who were transfusion free at baseline, 10 (48%) remained so over the same period.

The most common adverse reactions in 20% or more of patients were hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolonged, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.

The recommended dose varies by weight and concomitant use of strong CYP3A4 inhibitors. Because of an anticipated delay in commercial availability, the lowest strength dose of revumenib will be available through an expanded access program for patients who weigh < 40 kg.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved revumenib (Revuforj — Syndax Pharmaceuticals) for relapsed or refractory acute leukemia with a KMT2A gene translocation in adult and pediatric patients 1 year or older.

The approval makes the oral small-molecule menin inhibitor the first pharmaceutical to carry the indication. It blocks the binding of menin to mutated KMT2A fusion proteins, tamping down the process that leads to the disease.

Although a relatively uncommon form of leukemia, KMT2A rearrangements are a major driver of acute leukemia in infants.

Approval was based on a single-arm of the open-label AUGMENT-101 trial with 104 adult and pediatric patients with the mutation. Pediatric patients were at least 30 days old.

The rate of complete remission (CR) plus CR with partial hematologic recovery was 21.2% (22 patients) with a median duration of 6.4 months. The median time to remission was 1.9 months.

Eighty-three patients required blood cell and/or platelet transfusions at baseline; 12 (14%) did not need transfusions for 56 days afterward. Of the 21 who were transfusion free at baseline, 10 (48%) remained so over the same period.

The most common adverse reactions in 20% or more of patients were hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolonged, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.

The recommended dose varies by weight and concomitant use of strong CYP3A4 inhibitors. Because of an anticipated delay in commercial availability, the lowest strength dose of revumenib will be available through an expanded access program for patients who weigh < 40 kg.

A version of this article appeared on Medscape.com.