FDA/CDC

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

After more than 10 hours of intense debate, a Food and Drug Administration advisory panel gave its support to a premarket approval application (PMA) for the TransMedics Organ Care System (OCS) Heart system.

Courtesy Transmedics

The OCS Heart is a portable extracorporeal perfusion and monitoring system designed to keep a donor heart in a normothermic, beating state. The “heart in a box” technology allows donor hearts to be transported across longer distances than is possible with standard cold storage, which can safely preserve donor hearts for about 4 hours.

The Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 12 to 5, with 1 abstention, that the benefits of the OCS Heart System outweigh its risks.

The panel voted in favor of the OCS Heart being effective (10 yes, 6 no, and 2 abstaining) and safe (9 yes, 7 no, 2 abstaining) but not without mixed feelings.

James Blankenship, MD, a cardiologist at the University of New Mexico, Albuquerque, voted yes to all three questions but said: “If it had been compared to standard of care, I would have voted no to all three. But if it’s compared to getting an [left ventricular assist device] LVAD or not getting a heart at all, I would say the benefits outweigh the risks.”

Marc R. Katz, MD, chief of cardiothoracic surgery, Medical University of South Carolina, Charleston, also gave universal support, noting that the rate of heart transplantations has been flat for years. “This is a big step forward toward being able to expand that number. Now all that said, it obviously was a less-than-perfect study and I do think there needs to be some constraints put on the utilization.”

The panel reviewed data from the single-arm OCS Heart EXPAND trial and associated EXPAND Continued Access Protocol (CAP), as well the sponsor’s first OCS Heart trial, PROCEED II.

EXPAND met its effectiveness endpoint, with 88% of donor hearts successfully transplanted, an 8% incidence of severe primary graft dysfunction (PGD) 24 hours after transplantation, and 94.6% survival at 30 days.

Data from 41 patients with 30-day follow-up in the ongoing EXPAND CAP show 91% of donor hearts were utilized, a 2.4% incidence of severe PGD, and 100% 30-day survival.

The sponsor and the FDA clashed over changes made to the trial after the PMA was submitted, the appropriateness of the effectiveness outcome, and claims by the FDA that there was substantial overlap in demographic characteristics between the extended criteria donor hearts in the EXPAND trials and the standard criteria donor hearts in PROCEED II.

TransMedics previously submitted a PMA based on PROCEED II but it noted in submitted documents that it was withdrawn because of “fundamental disagreements with FDA” on the interpretation of a post hoc analysis with United Network for Organ Sharing registry data that identified increased all-cause mortality risk but comparable cardiac-related mortality in patients with OCS hearts.

During the marathon hearing, FDA officials presented several post hoc analyses, including one stratified by donor inclusion criteria, in which 30-day survival estimates were worse in recipients of single-criterion organs than for those receiving donor organs with multiple inclusion criteria (85% vs. 91.4%). In a second analysis, 2-year point estimates of survival also trended lower with donor organs having only one extended criterion.

Reported EXPAND CAP 6- and 12-month survival estimates were 100% and 93%, respectively, which was higher than EXPAND (93% and 84%), but there was substantial censoring (>50%) at 6 months and beyond, FDA officials said.

When EXPAND and CAP data were pooled, modeled survival curves shifted upward but there was a substantial site effect, with a single site contributing 46% of data, which may affect generalizability of the results, they noted.

“I voted yes for safety, no for efficacy, and no for approval and I’d just like to say I found this to be the most difficult vote in my experience on this panel,” John Hirshfeld, MD, University of Pennsylvania, Philadelphia, said. “I was very concerned that the PROCEED data suggests a possible harm, and in the absence of an interpretable comparator for the EXPAND trial, it’s really not possible to decide if there’s efficacy.”

Keith B. Allen, MD, director of surgical research at Saint Luke’s Hospital of Kansas City (Mo.), said, “I voted no on safety; I’m not going to give the company a pass. I think their animal data was sorely lacking and a lot of issues over the last 10 years could have been addressed with some key animal studies.

“For efficacy and risk/benefit, I voted yes for both,” he said. “Had this been standard of care and only PROCEED II, I would have voted no, but I do think there are a lot of hearts that go in the bucket and this is a challenging population.”

More than a dozen physicians and patients spoke at the open public hearing about the potential for the device to expand donor heart utilization, including a recipient whose own father died while waiting on the transplant list. Only about 3 out of every 10 donated hearts are used for transplant. To ensure fair access, particularly for patients in rural areas, federal changes in 2020 mandate that organs be allocated to the sickest patients first.

Data showed that the OCS Heart System was associated with shorter waiting list times, compared with U.S. averages but longer preservation times than cold static preservation.

In all, 13% of accepted donor organs were subsequently turned down after OCS heart preservation. Lactate levels were cited as the principal reason for turn-down but, FDA officials said, the validity of using lactate as a marker for transplantability is unclear.

Pathologic analysis of OCS Heart turned-down donor hearts with stable antemortem hemodynamics, normal or near-normal anatomy and normal ventricular function by echocardiography, and autopsy findings of acute diffuse or multifocal myocardial damage “suggest that in an important proportion of cases the OCS Heart system did not provide effective organ preservation or its use caused severe myocardial damage to what might have been an acceptable graft for transplant,” said Andrew Farb, MD, chief medical officer of the FDA’s Office of Cardiovascular Devices.
 

Proposed indication

In the present PMA, the OCS Heart System is indicated for donor hearts with one or more of the following characteristics: an expected cross-clamp or ischemic time of at least 4 hours because of donor or recipient characteristics; or an expected total cross-clamp time of at least 2 hours plus one of the following risk factors: donor age 55 or older, history of cardiac arrest and downtime of at least 20 minutes, history of alcoholism, history of diabetes, donor ejection fraction of 40%-50%,history of left ventricular hypertrophy, and donor angiogram with luminal irregularities but no significant coronary artery disease

Several members voiced concern about “indication creep” should the device be approved by the FDA, and highlighted the 2-hour cross-clamp time plus wide-ranging risk factors.

“I’m a surgeon and I voted no on all three counts,” said Murray H. Kwon, MD, Ronald Reagan University of California, Los Angeles Medical Center. “As far as risk/benefit, if it was just limited to one group – the 4-hour plus – I would say yes, but if you’re going to tell me that there’s a risk/benefit for the 2-hour with the alcoholic, I don’t know how that was proved in anything.”

Dr. Kwon was also troubled by lack of proper controls and by the one quarter of patients who ended up on mechanical circulatory support in the first 30 days after transplant. “I find that highly aberrant.”

Joaquin E. Cigarroa, MD, head of cardiovascular medicine, Oregon Health & Science University, Portland, said the unmet need for patients with refractory, end-stage heart failure is challenging and quite emotional, but also voted no across the board, citing concerns about a lack of comparator in the EXPAND trials and overall out-of-body ischemic time.

“As it relates to risk/benefit, I thought long and hard about voting yes despite all the unknowns because of this emotion, but ultimately I voted no because of the secondary 2-hours plus alcoholism, diabetes, or minor coronary disease, in which the ischemic burden and ongoing lactate production concern me,” he said.

Although the panel decision is nonbinding, there was strong support from the committee members for a randomized, postapproval trial and more complete animal studies.

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

The Food and Drug Administration has granted its first-ever approval of an artificial intelligence device to help find colon lesions during colonoscopy.

The GI Genius (Cosmo Artificial Intelligence) identifies areas of the colon where a colorectal polyp or tumor might be located. Clinicians then follow up with a closer examination and possible treatment.

“With the FDA’s authorization of this device today, clinicians now have a tool that could help improve their ability to detect gastrointestinal lesions they may have missed otherwise,” said Courtney H. Lias, PhD, acting director of the FDA’s gastrorenal, ob.gyn., general hospital, and urology devices office, in a media release.

The GI Genius consists of both hardware and software designed to work with an endoscope. It uses machine learning to recognize possible polyps during a colonoscopy. It marks these areas with green squares on the video generated by the endoscope’s camera and emits a short, low-volume sound. Clinicians decide if a lesion is truly present and whether to sample or remove such a lesion.

The device does not diagnose the lesions or recommend treatments and is not intended to take the place of laboratory sampling

The FDA based its approval on a trial in which 700 people aged 40-80 years underwent colonoscopies for colorectal cancer screening, surveillance, follow-up from positive results of a fecal occult blood test, or gastrointestinal symptoms of possible colon cancer.

Of these participants, 263 were being screened or surveilled every 3 years or more. The researchers randomly divided patients into a group of 136 who underwent white-light standard colonoscopy with the GI Genius, and 127 who underwent white-light standard colonoscopy without the GI Genius.

Using the GI Genius, clinicians identified adenomas or carcinomas that were later confirmed through lab results in 55.1% of patients. Without the GI Genius, the clinicians identified such lesions in 42.0% of patients.

The patients examined with the GI Genius received more biopsies, including slightly more that were not adenomas. But the biopsies did not lead to any adverse events such as perforations, infections, bleeding, or further biopsies.

More information on the GI Genius is available on the FDA website.

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

The Food and Drug Administration has granted its first-ever approval of an artificial intelligence device to help find colon lesions during colonoscopy.

The GI Genius (Cosmo Artificial Intelligence) identifies areas of the colon where a colorectal polyp or tumor might be located. Clinicians then follow up with a closer examination and possible treatment.

“With the FDA’s authorization of this device today, clinicians now have a tool that could help improve their ability to detect gastrointestinal lesions they may have missed otherwise,” said Courtney H. Lias, PhD, acting director of the FDA’s gastrorenal, ob.gyn., general hospital, and urology devices office, in a media release.

The GI Genius consists of both hardware and software designed to work with an endoscope. It uses machine learning to recognize possible polyps during a colonoscopy. It marks these areas with green squares on the video generated by the endoscope’s camera and emits a short, low-volume sound. Clinicians decide if a lesion is truly present and whether to sample or remove such a lesion.

The device does not diagnose the lesions or recommend treatments and is not intended to take the place of laboratory sampling

The FDA based its approval on a trial in which 700 people aged 40-80 years underwent colonoscopies for colorectal cancer screening, surveillance, follow-up from positive results of a fecal occult blood test, or gastrointestinal symptoms of possible colon cancer.

Of these participants, 263 were being screened or surveilled every 3 years or more. The researchers randomly divided patients into a group of 136 who underwent white-light standard colonoscopy with the GI Genius, and 127 who underwent white-light standard colonoscopy without the GI Genius.

Using the GI Genius, clinicians identified adenomas or carcinomas that were later confirmed through lab results in 55.1% of patients. Without the GI Genius, the clinicians identified such lesions in 42.0% of patients.

The patients examined with the GI Genius received more biopsies, including slightly more that were not adenomas. But the biopsies did not lead to any adverse events such as perforations, infections, bleeding, or further biopsies.

More information on the GI Genius is available on the FDA website.

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

The Food and Drug Administration has granted its first-ever approval of an artificial intelligence device to help find colon lesions during colonoscopy.

The GI Genius (Cosmo Artificial Intelligence) identifies areas of the colon where a colorectal polyp or tumor might be located. Clinicians then follow up with a closer examination and possible treatment.

“With the FDA’s authorization of this device today, clinicians now have a tool that could help improve their ability to detect gastrointestinal lesions they may have missed otherwise,” said Courtney H. Lias, PhD, acting director of the FDA’s gastrorenal, ob.gyn., general hospital, and urology devices office, in a media release.

The GI Genius consists of both hardware and software designed to work with an endoscope. It uses machine learning to recognize possible polyps during a colonoscopy. It marks these areas with green squares on the video generated by the endoscope’s camera and emits a short, low-volume sound. Clinicians decide if a lesion is truly present and whether to sample or remove such a lesion.

The device does not diagnose the lesions or recommend treatments and is not intended to take the place of laboratory sampling

The FDA based its approval on a trial in which 700 people aged 40-80 years underwent colonoscopies for colorectal cancer screening, surveillance, follow-up from positive results of a fecal occult blood test, or gastrointestinal symptoms of possible colon cancer.

Of these participants, 263 were being screened or surveilled every 3 years or more. The researchers randomly divided patients into a group of 136 who underwent white-light standard colonoscopy with the GI Genius, and 127 who underwent white-light standard colonoscopy without the GI Genius.

Using the GI Genius, clinicians identified adenomas or carcinomas that were later confirmed through lab results in 55.1% of patients. Without the GI Genius, the clinicians identified such lesions in 42.0% of patients.

The patients examined with the GI Genius received more biopsies, including slightly more that were not adenomas. But the biopsies did not lead to any adverse events such as perforations, infections, bleeding, or further biopsies.

More information on the GI Genius is available on the FDA website.

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

The U.S. Food and Drug Administration is warning health care providers about the risk for potentially life-threatening infections associated with reprocessed endoscopes used for viewing the urinary tract, including cystoscopes, cystouerthroscopes, and ureteroscopes.

The federal agency is investigating more than 450 medical device reports, including three reports of deaths, received between Jan. 1, 2017, and Feb. 20, 2021, that describe post-procedure infections and other possible contamination problems associated with the reprocessing or cleaning and sterilization of the devices.

Although it’s early in the investigation, on the basis of available data, the FDA believes the risk for infection is low.

“We are very concerned about the three reported deaths – outside of the United States – associated with these infections, and we’re acting fast to communicate with health care providers and the public about what we know and what is still an emerging issue,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement released on April 1.

Manufacturer Olympus Corporation submitted three reports of deaths attributed to a bacterial infection. In two of those reports, the infection was linked to a forceps/irrigation plug, an accessory component used to control water flow and enable access to the working channel of the endoscope. Lab tests confirmed that the bacteria that caused the infection was present in the forceps/irrigation plug.

The FDA said the third victim’s death involved a cystoscope that did not pass a leak test. It is possible that the damaged device was a factor in the patient’s becoming infected.

It’s not known to what degree the reported infections or patient comorbidities played a part in the patient deaths. The FDA also hasn’t concluded that any specific manufacturer or brand of these devices is associated with higher risks than others.

The FDA released recommendations for processing and using these devices and emphasized the importance of following manufacturers’ labeling and reprocessing instructions to minimize the risk for infection.

In addition to following reprocessing instructions, the recommendations include not using a device that has failed a leak test, developing schedules for routine device inspection and maintenance, and discussing the potential benefits and risks associated with procedures involving reprocessed urologic endoscopes with patients.

The newly reported concerns with urologic endoscopes are similar to problems associated with reprocessed duodenoscopes. In 2018, the FDA warned about higher-than-expected contamination rates for reprocessed duodenoscopes. The FDA has taken action on infections related to the reprocessing of duodenoscopes. In 2015, it required postmarket safety studies and the updating of sampling and culturing protocols. In 2019, the FDA approved single-use duodenoscopes in an effort to curb infections.

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

The U.S. Food and Drug Administration is warning health care providers about the risk for potentially life-threatening infections associated with reprocessed endoscopes used for viewing the urinary tract, including cystoscopes, cystouerthroscopes, and ureteroscopes.

The federal agency is investigating more than 450 medical device reports, including three reports of deaths, received between Jan. 1, 2017, and Feb. 20, 2021, that describe post-procedure infections and other possible contamination problems associated with the reprocessing or cleaning and sterilization of the devices.

Although it’s early in the investigation, on the basis of available data, the FDA believes the risk for infection is low.

“We are very concerned about the three reported deaths – outside of the United States – associated with these infections, and we’re acting fast to communicate with health care providers and the public about what we know and what is still an emerging issue,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement released on April 1.

Manufacturer Olympus Corporation submitted three reports of deaths attributed to a bacterial infection. In two of those reports, the infection was linked to a forceps/irrigation plug, an accessory component used to control water flow and enable access to the working channel of the endoscope. Lab tests confirmed that the bacteria that caused the infection was present in the forceps/irrigation plug.

The FDA said the third victim’s death involved a cystoscope that did not pass a leak test. It is possible that the damaged device was a factor in the patient’s becoming infected.

It’s not known to what degree the reported infections or patient comorbidities played a part in the patient deaths. The FDA also hasn’t concluded that any specific manufacturer or brand of these devices is associated with higher risks than others.

The FDA released recommendations for processing and using these devices and emphasized the importance of following manufacturers’ labeling and reprocessing instructions to minimize the risk for infection.

In addition to following reprocessing instructions, the recommendations include not using a device that has failed a leak test, developing schedules for routine device inspection and maintenance, and discussing the potential benefits and risks associated with procedures involving reprocessed urologic endoscopes with patients.

The newly reported concerns with urologic endoscopes are similar to problems associated with reprocessed duodenoscopes. In 2018, the FDA warned about higher-than-expected contamination rates for reprocessed duodenoscopes. The FDA has taken action on infections related to the reprocessing of duodenoscopes. In 2015, it required postmarket safety studies and the updating of sampling and culturing protocols. In 2019, the FDA approved single-use duodenoscopes in an effort to curb infections.

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

The U.S. Food and Drug Administration is warning health care providers about the risk for potentially life-threatening infections associated with reprocessed endoscopes used for viewing the urinary tract, including cystoscopes, cystouerthroscopes, and ureteroscopes.

The federal agency is investigating more than 450 medical device reports, including three reports of deaths, received between Jan. 1, 2017, and Feb. 20, 2021, that describe post-procedure infections and other possible contamination problems associated with the reprocessing or cleaning and sterilization of the devices.

Although it’s early in the investigation, on the basis of available data, the FDA believes the risk for infection is low.

“We are very concerned about the three reported deaths – outside of the United States – associated with these infections, and we’re acting fast to communicate with health care providers and the public about what we know and what is still an emerging issue,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement released on April 1.

Manufacturer Olympus Corporation submitted three reports of deaths attributed to a bacterial infection. In two of those reports, the infection was linked to a forceps/irrigation plug, an accessory component used to control water flow and enable access to the working channel of the endoscope. Lab tests confirmed that the bacteria that caused the infection was present in the forceps/irrigation plug.

The FDA said the third victim’s death involved a cystoscope that did not pass a leak test. It is possible that the damaged device was a factor in the patient’s becoming infected.

It’s not known to what degree the reported infections or patient comorbidities played a part in the patient deaths. The FDA also hasn’t concluded that any specific manufacturer or brand of these devices is associated with higher risks than others.

The FDA released recommendations for processing and using these devices and emphasized the importance of following manufacturers’ labeling and reprocessing instructions to minimize the risk for infection.

In addition to following reprocessing instructions, the recommendations include not using a device that has failed a leak test, developing schedules for routine device inspection and maintenance, and discussing the potential benefits and risks associated with procedures involving reprocessed urologic endoscopes with patients.

The newly reported concerns with urologic endoscopes are similar to problems associated with reprocessed duodenoscopes. In 2018, the FDA warned about higher-than-expected contamination rates for reprocessed duodenoscopes. The FDA has taken action on infections related to the reprocessing of duodenoscopes. In 2015, it required postmarket safety studies and the updating of sampling and culturing protocols. In 2019, the FDA approved single-use duodenoscopes in an effort to curb infections.

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

The list of medical comorbidities associated with high risk for severe COVID-19 now includes moderate to severe asthma, diabetes, and substance use disorders, according to the Centers for Disease Control and Prevention.

The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.

On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.

[email protected]

The list of medical comorbidities associated with high risk for severe COVID-19 now includes moderate to severe asthma, diabetes, and substance use disorders, according to the Centers for Disease Control and Prevention.

The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.

On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.

[email protected]

The list of medical comorbidities associated with high risk for severe COVID-19 now includes moderate to severe asthma, diabetes, and substance use disorders, according to the Centers for Disease Control and Prevention.

The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.

On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.

[email protected]

The Food and Drug Administration has approved the nonstimulant medication viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals) for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged 6-17 years, the company has announced.

Viloxazine (formerly SPN-812) is a selective norepinephrine reuptake inhibitor. Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce, as needed.

The approval of viloxazine is supported by data from four phase 3 clinical trials involving more than 1,000 pediatric patients aged 6-17 years, the company said.

In one randomized, placebo-controlled phase 3 study that included more than 400 children, viloxazine reduced symptoms of ADHD as soon as 1 week after dosing and was well tolerated.

As reported by this news organization, the study was published last July in Clinical Therapeutics.

In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical associate professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interview.

Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.

The prescribing label for viloxazine includes a boxed warning regarding the potential for suicidal thoughts and behaviors in some children with ADHD treated with the drug, especially within the first few months of treatment or when the dose is changed. 

In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with viloxazine than in patients treated with placebo. Patients taking viloxazine should be closely monitored for any new or sudden changes in mood, behavior, thoughts, and feelings.

Viloxazine has shown promise in a phase 3 trial involving adults with ADHD.

The company plans to submit a supplemental new drug application to the FDA for viloxazine in adults later this year.

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

The Food and Drug Administration has approved the nonstimulant medication viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals) for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged 6-17 years, the company has announced.

Viloxazine (formerly SPN-812) is a selective norepinephrine reuptake inhibitor. Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce, as needed.

The approval of viloxazine is supported by data from four phase 3 clinical trials involving more than 1,000 pediatric patients aged 6-17 years, the company said.

In one randomized, placebo-controlled phase 3 study that included more than 400 children, viloxazine reduced symptoms of ADHD as soon as 1 week after dosing and was well tolerated.

As reported by this news organization, the study was published last July in Clinical Therapeutics.

In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical associate professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interview.

Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.

The prescribing label for viloxazine includes a boxed warning regarding the potential for suicidal thoughts and behaviors in some children with ADHD treated with the drug, especially within the first few months of treatment or when the dose is changed. 

In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with viloxazine than in patients treated with placebo. Patients taking viloxazine should be closely monitored for any new or sudden changes in mood, behavior, thoughts, and feelings.

Viloxazine has shown promise in a phase 3 trial involving adults with ADHD.

The company plans to submit a supplemental new drug application to the FDA for viloxazine in adults later this year.

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

The Food and Drug Administration has approved the nonstimulant medication viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals) for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged 6-17 years, the company has announced.

Viloxazine (formerly SPN-812) is a selective norepinephrine reuptake inhibitor. Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce, as needed.

The approval of viloxazine is supported by data from four phase 3 clinical trials involving more than 1,000 pediatric patients aged 6-17 years, the company said.

In one randomized, placebo-controlled phase 3 study that included more than 400 children, viloxazine reduced symptoms of ADHD as soon as 1 week after dosing and was well tolerated.

As reported by this news organization, the study was published last July in Clinical Therapeutics.

In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical associate professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interview.

Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.

The prescribing label for viloxazine includes a boxed warning regarding the potential for suicidal thoughts and behaviors in some children with ADHD treated with the drug, especially within the first few months of treatment or when the dose is changed. 

In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with viloxazine than in patients treated with placebo. Patients taking viloxazine should be closely monitored for any new or sudden changes in mood, behavior, thoughts, and feelings.

Viloxazine has shown promise in a phase 3 trial involving adults with ADHD.

The company plans to submit a supplemental new drug application to the FDA for viloxazine in adults later this year.

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

The Food and Drug Administration has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older.

Olivier Le Moal/Getty Images

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

“This approval will help enable appropriate children and adults with diabetes to be able to address sudden and severe hypoglycemia, which can quickly progress from a mild event to an emergency,” Jeremy Pettus, MD, assistant professor of medicine at the University of California, San Diego, said in a company statement.

The approval marks the latest step in the development of newer glucagon formulations that are easier to use in hypoglycemic emergencies than the traditional formulation that requires several steps for reconstitution.

The first intranasal glucagon (Baqsimi, Eli Lilly) was approved in the United States in July 2019 for people with diabetes age 4 years and older.

In September 2019, the FDA approved another prefilled glucagon rescue pen (Gvoke HypoPen, Xeris Pharmaceuticals) for the treatment of severe hypoglycemia in adult and pediatric patients age 2 years and older with diabetes.

Dasiglucagon is currently in phase 3 trials as a subcutaneous infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled, phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection-site pain in both children and adults. Diarrhea was also reported in adults.  

Full launch is expected in late June 2021.

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

The Food and Drug Administration has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older.

Olivier Le Moal/Getty Images

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

“This approval will help enable appropriate children and adults with diabetes to be able to address sudden and severe hypoglycemia, which can quickly progress from a mild event to an emergency,” Jeremy Pettus, MD, assistant professor of medicine at the University of California, San Diego, said in a company statement.

The approval marks the latest step in the development of newer glucagon formulations that are easier to use in hypoglycemic emergencies than the traditional formulation that requires several steps for reconstitution.

The first intranasal glucagon (Baqsimi, Eli Lilly) was approved in the United States in July 2019 for people with diabetes age 4 years and older.

In September 2019, the FDA approved another prefilled glucagon rescue pen (Gvoke HypoPen, Xeris Pharmaceuticals) for the treatment of severe hypoglycemia in adult and pediatric patients age 2 years and older with diabetes.

Dasiglucagon is currently in phase 3 trials as a subcutaneous infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled, phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection-site pain in both children and adults. Diarrhea was also reported in adults.  

Full launch is expected in late June 2021.

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

The Food and Drug Administration has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older.

Olivier Le Moal/Getty Images

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

“This approval will help enable appropriate children and adults with diabetes to be able to address sudden and severe hypoglycemia, which can quickly progress from a mild event to an emergency,” Jeremy Pettus, MD, assistant professor of medicine at the University of California, San Diego, said in a company statement.

The approval marks the latest step in the development of newer glucagon formulations that are easier to use in hypoglycemic emergencies than the traditional formulation that requires several steps for reconstitution.

The first intranasal glucagon (Baqsimi, Eli Lilly) was approved in the United States in July 2019 for people with diabetes age 4 years and older.

In September 2019, the FDA approved another prefilled glucagon rescue pen (Gvoke HypoPen, Xeris Pharmaceuticals) for the treatment of severe hypoglycemia in adult and pediatric patients age 2 years and older with diabetes.

Dasiglucagon is currently in phase 3 trials as a subcutaneous infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled, phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection-site pain in both children and adults. Diarrhea was also reported in adults.  

Full launch is expected in late June 2021.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Food and Drug Administration has approved alirocumab (Praluent, Regeneron Pharmaceuticals) injection as add-on therapy for adults with homozygous familial hypercholesterolemia, the agency announced.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was originally approved in the United States in 2015 as an adjunct to diet, alone or in combination with other lipid-lowering therapies, to reduce LDL cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (FH).

Heterozygous FH is one of the most common genetic disorders, affecting 1 in every 200-500 people worldwide, whereas homozygous FH is very rare, affecting about 1 in 1 million people worldwide.

Alirocumab is also approved to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

The new indication is based on a 12-week randomized trial in 45 adults who received 150 mg alirocumab every 2 weeks and 24 patients who received placebo, both on top of other therapies to reduce LDL cholesterol. At week 12, patients receiving alirocumab had an average 27% decrease in LDL cholesterol, compared with an average 9% increase among patients on placebo.

Common side effects of alirocumab are nasopharyngitis, injection-site reactions, and influenza. Serious hypersensitivity reactions have occurred among people taking alirocumab.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Food and Drug Administration has expanded the indication for mirabegron (Myrbetriq/Myrbetriq Granules) to treat neurogenic detrusor overactivity (NDO), a bladder dysfunction related to neurologic impairment, in children aged 3 years and older.

This comes 1 year after the FDA approved solifenacin succinate, the first treatment of NDO in pediatric patients aged 2 years and older.

The approval of the drug for these new indications is a “positive step” for the treatment of NDO in young patients, Christine P. Nguyen, MD, director of the FDA’s Division of Urology, Obstetrics, and Gynecology, said in an FDA statement.

“Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients,” Dr. Nguyen said.

NDO is a bladder dysfunction that frequently occurs in patients with congenital conditions, such as spina bifida. It also occurs in people who suffer from other diseases or injuries of the nervous system, such as multiple sclerosis and spinal cord injury. Symptoms of the condition include urinary frequency and incontinence.

The condition is characterized by the overactivity of the bladder wall muscle, which is normally relaxed to allow storage of urine. Irregular bladder muscle contraction increases storage pressure and decreases the amount of urine the bladder can hold. This can also put the upper urinary tract at risk for deterioration and cause permanent damage to the kidneys.

The effectiveness of Myrbetriq and Myrbetriq Granules for pediatric NDO was determined in a study of 86 children and adolescents aged 3-17 years. The researchers found that after 24 weeks of treatment, the drug improved the patients’ bladder capacity, reduced the number of bladder wall muscle contractions, and improved the volume of urine that could be held. It also reduced the daily number of episodes of leakage.

Side effects of Myrbetriq and Myrbetriq Granules include urinary tract infection, cold symptoms, angioedema, constipation, and headache. The FDA said the drug may also increase blood pressure and may worsen blood pressure in patients who have a history of hypertension.

The FDA approved mirabegron in 2012 to treat overactive bladder in adults.

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

The Food and Drug Administration has expanded the indication for mirabegron (Myrbetriq/Myrbetriq Granules) to treat neurogenic detrusor overactivity (NDO), a bladder dysfunction related to neurologic impairment, in children aged 3 years and older.

This comes 1 year after the FDA approved solifenacin succinate, the first treatment of NDO in pediatric patients aged 2 years and older.

The approval of the drug for these new indications is a “positive step” for the treatment of NDO in young patients, Christine P. Nguyen, MD, director of the FDA’s Division of Urology, Obstetrics, and Gynecology, said in an FDA statement.

“Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients,” Dr. Nguyen said.

NDO is a bladder dysfunction that frequently occurs in patients with congenital conditions, such as spina bifida. It also occurs in people who suffer from other diseases or injuries of the nervous system, such as multiple sclerosis and spinal cord injury. Symptoms of the condition include urinary frequency and incontinence.

The condition is characterized by the overactivity of the bladder wall muscle, which is normally relaxed to allow storage of urine. Irregular bladder muscle contraction increases storage pressure and decreases the amount of urine the bladder can hold. This can also put the upper urinary tract at risk for deterioration and cause permanent damage to the kidneys.

The effectiveness of Myrbetriq and Myrbetriq Granules for pediatric NDO was determined in a study of 86 children and adolescents aged 3-17 years. The researchers found that after 24 weeks of treatment, the drug improved the patients’ bladder capacity, reduced the number of bladder wall muscle contractions, and improved the volume of urine that could be held. It also reduced the daily number of episodes of leakage.

Side effects of Myrbetriq and Myrbetriq Granules include urinary tract infection, cold symptoms, angioedema, constipation, and headache. The FDA said the drug may also increase blood pressure and may worsen blood pressure in patients who have a history of hypertension.

The FDA approved mirabegron in 2012 to treat overactive bladder in adults.

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

The Food and Drug Administration has expanded the indication for mirabegron (Myrbetriq/Myrbetriq Granules) to treat neurogenic detrusor overactivity (NDO), a bladder dysfunction related to neurologic impairment, in children aged 3 years and older.

This comes 1 year after the FDA approved solifenacin succinate, the first treatment of NDO in pediatric patients aged 2 years and older.

The approval of the drug for these new indications is a “positive step” for the treatment of NDO in young patients, Christine P. Nguyen, MD, director of the FDA’s Division of Urology, Obstetrics, and Gynecology, said in an FDA statement.

“Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients,” Dr. Nguyen said.

NDO is a bladder dysfunction that frequently occurs in patients with congenital conditions, such as spina bifida. It also occurs in people who suffer from other diseases or injuries of the nervous system, such as multiple sclerosis and spinal cord injury. Symptoms of the condition include urinary frequency and incontinence.

The condition is characterized by the overactivity of the bladder wall muscle, which is normally relaxed to allow storage of urine. Irregular bladder muscle contraction increases storage pressure and decreases the amount of urine the bladder can hold. This can also put the upper urinary tract at risk for deterioration and cause permanent damage to the kidneys.

The effectiveness of Myrbetriq and Myrbetriq Granules for pediatric NDO was determined in a study of 86 children and adolescents aged 3-17 years. The researchers found that after 24 weeks of treatment, the drug improved the patients’ bladder capacity, reduced the number of bladder wall muscle contractions, and improved the volume of urine that could be held. It also reduced the daily number of episodes of leakage.

Side effects of Myrbetriq and Myrbetriq Granules include urinary tract infection, cold symptoms, angioedema, constipation, and headache. The FDA said the drug may also increase blood pressure and may worsen blood pressure in patients who have a history of hypertension.

The FDA approved mirabegron in 2012 to treat overactive bladder in adults.

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

Chimeric antigen receptor (CAR) T-cell therapy, described as a “living drug,” is now available for patients with relapsed/refractory multiple myeloma who have been treated with four or more prior lines of therapy.

The Food and Drug Administration said these patients represent an “unmet medical need” when it granted approval for the new product – idecabtagene vicleucel (ide-cel; Abecma), developed by bluebird bio and Bristol-Myers Squibb.

Ide-cel is the first CAR T-cell therapy to gain approval for use in multiple myeloma. It is also the first CAR T-cell therapy to target B-cell maturation antigen.

Previously approved CAR T-cell products target CD19 and have been approved for use in certain types of leukemia and lymphoma.

All the CAR T-cell therapies are customized treatments that are created specifically for each individual patient from their own blood. The patient’s own T cells are removed from the blood, are genetically modified and expanded, and are then infused back into the patient. These modified T cells then seek out and destroy blood cancer cells, and they continue to do so long term.

In some patients, this has led to eradication of disease that had previously progressed with every other treatment that had been tried – results that have been described as “absolutely remarkable” and “one-shot therapy that looks to be curative.”

However, this cell therapy comes with serious adverse effects, including neurologic toxicity and cytokine release syndrome (CRS), which can be life threatening. For this reason, all these products have a risk evaluation and mitigation strategy, and the use of CAR T-cell therapies is limited to designated centers.

In addition, these CAR T-cells products are phenomenally expensive; hospitals have reported heavy financial losses with their use, and patients have turned to crowdfunding to pay for these therapies.
 

‘Phenomenal’ results in MM

The FDA noted that approval of ide-cel for multiple myeloma is based on data from a multicenter study that involved 127 patients with relapsed/refractory disease who had received at least three prior lines of treatment.

The results from this trial were published Feb. 25 in the New England Journal of Medicine.

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel told this news organization at the time.

The lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for patients with relapsed/refractory disease. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.

Nevertheless, in some patients, the disease continues to progress. For patients for whom treatments with all three classes of drugs have failed, the median progression-free survival is 3-4 months, and the median overall survival is 9 months.

In contrast, the results reported in the NEJM article showed that overall median progression-free survival was 8.8 months, but it was more than double that (20.2 months) for patients who achieved a complete or stringent complete response.

Estimated median overall survival was 19.4 months, and the overall survival was 78% at 12 months. The authors note that overall survival data are not yet mature.

The patients who were enrolled in the CAR T-cell trial had undergone many previous treatments. They had undergone a median of six prior drug therapies (range, 3-16), and most of the patients (120, 94%) had also undergone autologous hematopoietic stem cell transplant.

In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

In the NEJM article, the authors report that about a third of patients had a complete response to CAR T-cell therapy.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001); 42 (33%) showed a complete or stringent complete response; and 67 patients (52%) showed a “very good partial response or better,” they write.

In the FDA announcement of the product approval, the figures for complete response were slightly lower. “Of those studied, 28% of patients showed complete response – or disappearance of all signs of multiple myeloma – to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months,” the agency noted.

The FDA also noted that treatment with Abecma can cause severe side effects. The label carries a boxed warning regarding CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life threatening.

The most common side effects of Abecma are CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first 1-2 weeks after treatment, but some side effects may occur later.

The agency also noted that, to further evaluate the long-term safety of the drug, it is requiring the manufacturer to conduct a postmarketing observational study.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

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

Chimeric antigen receptor (CAR) T-cell therapy, described as a “living drug,” is now available for patients with relapsed/refractory multiple myeloma who have been treated with four or more prior lines of therapy.

The Food and Drug Administration said these patients represent an “unmet medical need” when it granted approval for the new product – idecabtagene vicleucel (ide-cel; Abecma), developed by bluebird bio and Bristol-Myers Squibb.

Ide-cel is the first CAR T-cell therapy to gain approval for use in multiple myeloma. It is also the first CAR T-cell therapy to target B-cell maturation antigen.

Previously approved CAR T-cell products target CD19 and have been approved for use in certain types of leukemia and lymphoma.

All the CAR T-cell therapies are customized treatments that are created specifically for each individual patient from their own blood. The patient’s own T cells are removed from the blood, are genetically modified and expanded, and are then infused back into the patient. These modified T cells then seek out and destroy blood cancer cells, and they continue to do so long term.

In some patients, this has led to eradication of disease that had previously progressed with every other treatment that had been tried – results that have been described as “absolutely remarkable” and “one-shot therapy that looks to be curative.”

However, this cell therapy comes with serious adverse effects, including neurologic toxicity and cytokine release syndrome (CRS), which can be life threatening. For this reason, all these products have a risk evaluation and mitigation strategy, and the use of CAR T-cell therapies is limited to designated centers.

In addition, these CAR T-cells products are phenomenally expensive; hospitals have reported heavy financial losses with their use, and patients have turned to crowdfunding to pay for these therapies.
 

‘Phenomenal’ results in MM

The FDA noted that approval of ide-cel for multiple myeloma is based on data from a multicenter study that involved 127 patients with relapsed/refractory disease who had received at least three prior lines of treatment.

The results from this trial were published Feb. 25 in the New England Journal of Medicine.

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel told this news organization at the time.

The lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for patients with relapsed/refractory disease. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.

Nevertheless, in some patients, the disease continues to progress. For patients for whom treatments with all three classes of drugs have failed, the median progression-free survival is 3-4 months, and the median overall survival is 9 months.

In contrast, the results reported in the NEJM article showed that overall median progression-free survival was 8.8 months, but it was more than double that (20.2 months) for patients who achieved a complete or stringent complete response.

Estimated median overall survival was 19.4 months, and the overall survival was 78% at 12 months. The authors note that overall survival data are not yet mature.

The patients who were enrolled in the CAR T-cell trial had undergone many previous treatments. They had undergone a median of six prior drug therapies (range, 3-16), and most of the patients (120, 94%) had also undergone autologous hematopoietic stem cell transplant.

In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

In the NEJM article, the authors report that about a third of patients had a complete response to CAR T-cell therapy.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001); 42 (33%) showed a complete or stringent complete response; and 67 patients (52%) showed a “very good partial response or better,” they write.

In the FDA announcement of the product approval, the figures for complete response were slightly lower. “Of those studied, 28% of patients showed complete response – or disappearance of all signs of multiple myeloma – to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months,” the agency noted.

The FDA also noted that treatment with Abecma can cause severe side effects. The label carries a boxed warning regarding CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life threatening.

The most common side effects of Abecma are CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first 1-2 weeks after treatment, but some side effects may occur later.

The agency also noted that, to further evaluate the long-term safety of the drug, it is requiring the manufacturer to conduct a postmarketing observational study.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

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

Chimeric antigen receptor (CAR) T-cell therapy, described as a “living drug,” is now available for patients with relapsed/refractory multiple myeloma who have been treated with four or more prior lines of therapy.

The Food and Drug Administration said these patients represent an “unmet medical need” when it granted approval for the new product – idecabtagene vicleucel (ide-cel; Abecma), developed by bluebird bio and Bristol-Myers Squibb.

Ide-cel is the first CAR T-cell therapy to gain approval for use in multiple myeloma. It is also the first CAR T-cell therapy to target B-cell maturation antigen.

Previously approved CAR T-cell products target CD19 and have been approved for use in certain types of leukemia and lymphoma.

All the CAR T-cell therapies are customized treatments that are created specifically for each individual patient from their own blood. The patient’s own T cells are removed from the blood, are genetically modified and expanded, and are then infused back into the patient. These modified T cells then seek out and destroy blood cancer cells, and they continue to do so long term.

In some patients, this has led to eradication of disease that had previously progressed with every other treatment that had been tried – results that have been described as “absolutely remarkable” and “one-shot therapy that looks to be curative.”

However, this cell therapy comes with serious adverse effects, including neurologic toxicity and cytokine release syndrome (CRS), which can be life threatening. For this reason, all these products have a risk evaluation and mitigation strategy, and the use of CAR T-cell therapies is limited to designated centers.

In addition, these CAR T-cells products are phenomenally expensive; hospitals have reported heavy financial losses with their use, and patients have turned to crowdfunding to pay for these therapies.
 

‘Phenomenal’ results in MM

The FDA noted that approval of ide-cel for multiple myeloma is based on data from a multicenter study that involved 127 patients with relapsed/refractory disease who had received at least three prior lines of treatment.

The results from this trial were published Feb. 25 in the New England Journal of Medicine.

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel told this news organization at the time.

The lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, commented: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for patients with relapsed/refractory disease. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.

Nevertheless, in some patients, the disease continues to progress. For patients for whom treatments with all three classes of drugs have failed, the median progression-free survival is 3-4 months, and the median overall survival is 9 months.

In contrast, the results reported in the NEJM article showed that overall median progression-free survival was 8.8 months, but it was more than double that (20.2 months) for patients who achieved a complete or stringent complete response.

Estimated median overall survival was 19.4 months, and the overall survival was 78% at 12 months. The authors note that overall survival data are not yet mature.

The patients who were enrolled in the CAR T-cell trial had undergone many previous treatments. They had undergone a median of six prior drug therapies (range, 3-16), and most of the patients (120, 94%) had also undergone autologous hematopoietic stem cell transplant.

In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta-exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta-refractory.

In the NEJM article, the authors report that about a third of patients had a complete response to CAR T-cell therapy.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001); 42 (33%) showed a complete or stringent complete response; and 67 patients (52%) showed a “very good partial response or better,” they write.

In the FDA announcement of the product approval, the figures for complete response were slightly lower. “Of those studied, 28% of patients showed complete response – or disappearance of all signs of multiple myeloma – to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months,” the agency noted.

The FDA also noted that treatment with Abecma can cause severe side effects. The label carries a boxed warning regarding CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life threatening.

The most common side effects of Abecma are CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first 1-2 weeks after treatment, but some side effects may occur later.

The agency also noted that, to further evaluate the long-term safety of the drug, it is requiring the manufacturer to conduct a postmarketing observational study.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

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