Health experts want FDA safety review of fast-tracked Alzheimer’s drug

Doctors and scientists are asking the Food and Drug Administration to convene an expert panel to review safety concerns About the Alzheimer’s disease treatment that received fast track approval in January.

Big picture: This is the latest concern about whether the FDA is cutting corners in evaluating Alzheimer’s drugs, prompted by the controversial 2021. Biogen Approval of Aduhelmwhich overcame advisory board objections and without evidence that the drug actually slowed the decline in memory and brain function.

• Some health experts now say the authorities are not doing enough to address the issue with Eisai’s lecanemab.
• The FDA gave the go-ahead for expedited approval last month after convening an advisory panel instead of following its customary process.
• Accelerated approval is based on the variables that the drug is likely to work rather than actual clinical results.
• Late last year, Congress gave the FDA greater authority over confirmatory trials that are supposed to prove a drug’s efficacy.
• recently National Academy of Sciences, Academy of Engineering and Medicine According to Cowen’s policy note, at the workshop, FDA officials were told they needed to be more transparent about the rationale for using the fast-track process in new areas other than cancer drugs and infectious diseases. rice field.

what’s happening: Some health experts believe Eisai’s drug should be convened for public debate before deciding whether it should be given full approval based on its actual clinical benefit.

• As we wrote An underlying concern during the Aduhelm controversy is that the FDA’s decision could undermine medical standards and give millions of patients false hope. Might be so Work can unlock perverse incentives.

Catch up soon: FDA in early January Eisai’s Accelerated Approval of Lecanemab — Sold at Leqembi — Large-scale clinical trial results Published in New England Journal of Medicine It can slow disease progression by 27% and slow the rate of cognitive decline over 18 months.

• This study showed that patients who took lecanemab showed: more side effects than placebo.
• Eisai reported 13 deaths out of approximately 1,800 trial participants. However, the company has not released details about the deaths, so scientists were unable to independently determine whether lecanemab was related to them. chemistry report.

What they say: “[C]”Significant questions remain as to whether the benefits outweigh the reported risks of brain swelling, cerebral hemorrhage and death in patients receiving this drug,” the independent advocacy group said. doctors for america said in a statement.

• “As physicians, we pledge to ‘do no harm’ in treating our patients, and we are committed to unbiased FDA approval decisions to inform that the benefits of an approved treatment truly outweigh its risks. We expect the FDA to provide independent guidance,” they added.

Line spacing: Eisai researchers suggest that people with Alzheimer’s disease are willing to take drugs with health risks if they can slow the progression of the disease. “They’re willing to risk brain hemorrhages,” one of the principal investigators, Sharon Cohen, said in November.

• “I don’t think it’s much different than an anticancer drug,” said Howard Filitt, co-founder and chief scientific officer of the Alzheimer’s Drug Discovery Foundation, even if there are side effects that can reduce quality. These drugs are approved, he added, even if the
• “We’re seeing an increase in cognitive longevity, that is, people’s ability to think, drive, and do other things,” said Filitt. “For older people, this is very important. I think,” he added.

State of play: a report of nature review neurology Although the lecanemab trial represents a “significant milestone,” they found that a “thorough evaluation of the data” is still needed to show whether the results are clinically meaningful.

• Alzheimer’s disease “is a condition that progresses very slowly without treatment, so we add treatment to slow it down a bit,” but “it’s not something that patients and families perceive on a daily basis.” , said Constantine Ricketsos, an Alzheimer’s researcher at Johns Hopkins Medical School.

detail: Lecanemab targets amyloid plaques, proteins in the brain thought to contribute to the development of Alzheimer’s disease.

• Early approval is NEJM This is for a Phase II trial that investigated patient cognitive scores as the primary clinical endpoint. The drug actually failed to meet the required score on the primary endpoint and was instead given approval based on a surrogate endpoint or variable showing reduction in amyloid plaques.

Zoom in: The presence of amyloid is measured by PET scan. However, there is no conclusive evidence that PET amyloid beta scanning is “reasonable and necessary” for the diagnosis or treatment of Alzheimer’s disease. Medicare and Medicaid Service Center.

• Jason Karlawish, a professor at the University of Pennsylvania Perelman School of Medicine, said: He said an independent committee would need to meet.
• Lecanemab is the third drug the FDA has used a beta-amyloid PET scan to “decide whether to grant accelerated approval, but we have not publicly discussed the data supporting the use of that endpoint,” Karlawish said. added Mr. .

note: In the FDA’s summary for accelerated approval, the agency said it “has not yet been submitted to the agency for review.” NEJM This study appears to support the clinical benefits of this drug.

• Reshma Ramachandran, an assistant professor at Yale School of Medicine, said, “It was amazing to see them making a bit of a big deal by talking about data from clinical trials they hadn’t reviewed yet. .

don’t forget: The FDA is currently evaluating three Alzheimer’s drugs based on the amyloid hypothesis and measured by beta-amyloid PET scans. Aduhelm, lecanemab, and Eli Lily’s donanemab. The latter has not received FDA accelerated approval.

What we see: Some FDA advisers do not believe an expert panel meeting is necessary.

• “I don’t think this data calls for it,” said Liana Apostolova, a neurologist at the Indiana University School of Medicine and a member of the FDA’s Peripheral and Central Nervous System Drug Advisory Committee.
• “Historically, very positive results from trials on multiple results and biomarkers have not been sent to an advisory board,” she added.
• Apostolova told Axios that she has worked as a consultant on Eisai’s lecanemab and as a result will not attend an advisory council if called.