ANDThe companies said Tuesday that Biogen and Eisai’s investigational Alzheimer’s disease treatment slowed the rate of cognitive decline by 27% in a clinical trial, meeting the targets of a closely monitored study, strengthening the drug’s approval status as early as January.
The positive outcome is welcome news for the millions of people living with Alzheimer’s, and a big win for Eisai and Biogen, giving companies a potential blockbuster product in intravenous medicine called lecanemab. For Biogen presiding Disastrous presentation of Alzheimer’s treatment AduhelmThe potential approval of lecanemab offers a rare second chance in a multi-billion dollar market.
Eisai CEO Haruo Naito said in a statement that the lecanemab study is “an important milestone for Eisai in fulfilling our mission to meet the expectations of the Alzheimer’s disease community.”
In the study, which included approximately 1,800 early-stage Alzheimer’s patients, lecanemab outperformed placebo. The treatment also met its secondary goals of reducing toxic plaques in the brain and slowing the patients’ decline in three other measures of memory and function.
Approximately 21% of patients treated with lecanemab experienced brain swelling visible on PET scans, a side effect associated with its type of medication. The companies said less than 3% of these patients had cases of symptomatic swelling.
The CLARITY-AD study was the largest to date. long debated theory That clearing toxic brain plaques called amyloid may slow the rate of Alzheimer’s by slowing the rate of memory loss or delaying the onset of dementia.
Lecanemab is the first treatment of its kind to confirm the so-called amyloid hypothesis in a large Phase 3 clinical trial after two decades of consistent failure and darker results from similar, experimental drugs.
“This is a statistically robust and positive study, but the treatment effect is small,” said Lon Schneider, MD, a physician and Alzheimer’s specialist at the University of Southern California Keck School of Medicine. Schneider cautioned that experts will need to take a much closer look at the lecanemab data when presented in more detail, but based on the results described in Eisai’s press release, he believes lecanemab will gain approval from the Food and Drug Administration. Schneider was not included in the study.
The FDA is already considering lecanemab for conditional approval and promises to make a decision by January. 6 is based on preliminary evidence from a smaller study showing the drug’s effect on amyloid in patients’ brains. Eisai now plans to incorporate more conclusive results from the CLARITY-AD study into her practice, aiming to gain full approval by the summer and convince Medicare to step back. restrictive refund policy It was founded after Aduhelm.
CLARITY-AD may be enough to win the FDA, but the future of lecanemab depends on whether doctors, payers and patients find the supporting data convincing. The study used a metric called Clinical Dementia Rating totals, or CDR-SB, that measures six cognitive domains, including memory, problem solving, and self-care, and produced scores ranging from 0 to 18, with higher numbers indicating more severe dementia. .
In the 18-month trial, patients who received lecanemab performed .45 points better on the test than those who received placebo; it’s a result that reaches the threshold of statistical significance, so it’s unlikely to be the result of random chance.
In a comparable clinical trial, Aduhelm slowed decline by 22% and outperformed placebo by 0.39 points on the same measure. A second, identical run failed.
Lecanemab was administered as an intravenous infusion twice a month. About 25% of the 1,800 participants in the CLARITY-AD study were Hispanic and African-American, making it one of the most diverse populations participating in an Alzheimer’s clinical trial.
For lecanemab, statistical significance does not necessarily mean it is a life-changing drug. Alzheimer’s researchers have spent years debating what small changes in CDR-SB scores mean for patients with the disease. A partial improvement on an 18-point scale may not be noticeable in real life. On the other hand, the metric is not a range scale, that is, their numerical differences are not proportional to each other. Going from 1 to 1.5 in CDR-SB may mean you can no longer drive on your own, while going from 14 to 14.5 would probably make little difference for a patient already suffering from dementia.
The rate of brain swelling in the lecanemab study can be confusing, according to Michael Greicius, a neurologist who studies and treats Alzheimer’s at Stanford University. When patients have a common side-effect called ARIA, everyone involved in the study can be pretty sure they are taking the drug and not the placebo, thus biasing the study. Greicius said he will look to see if a real test of lecanemab’s benefits only helps patients who don’t test positive for ARIA.
“I think this will be at the peak of what is considered to be the least clinically significant, and it may be below that,” said Greicius, who was not involved in the study. “This is where we need to see more data.”
Any definitive decision on lecanemab’s value will require more detailed results from CLARITY-AD, which Eisai promised to present at a medical conference in November, experts said.
Wall Street had only moderate expectations for CLARITY-AD, with analysts identifying a low probability of success and declaring that even a marginal benefit would be considered positive for Biogen and Eisai. Since Aduhelm’s 2021 approval, Biogen’s share price has dropped nearly 50% and Eisai has lost about 60% of its value.
“Today’s announcement hopes patients and their families that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease and provide a clinically meaningful effect on cognition and function,” Biogen CEO Michel Vounatsos said in a statement.
The results start a transformational nine-month period for Alzheimer’s research. By the end of this year, Roche will have data from a two-year dual study on gantenerumab, another antibody that reduces brain plaques. And in the first half of 2023, Eli Lilly hopes to see results from a Phase 3 trial on donanemab, a similar treatment that met its goals in a small study last year.