An Biogen and Eisai’s experimental Alzheimer’s disease treatment slowed the rate of cognitive decline by 27% in a clinical trial, the companies said on Tuesday, meeting the goals of a closely watched study and bolstering the case of the drug for approval as early as January.
The positive result is good news for the millions of people with Alzheimer’s disease and a big win for Eisai and Biogen, giving the companies a potential breakthrough product in intravenous medicine called lecanemab. For Biogen, which presided over the disastrous rollout of Alzheimer’s disease treatment Aduhelm, the potential approval of lecanemab presents a rare second chance in a multi-billion dollar market.
The lecanemab study is an “important step for Eisai in fulfilling our mission to meet the expectations of the Alzheimer’s disease community,” Eisai CEO Haruo Naito said in a statement.
In the study, which recruited around 1,800 patients with early-stage Alzheimer’s disease, lecanemab outperformed placebo. The treatment also achieved its secondary goals of reducing toxic plaques in the brain and slowing the patients’ decline on three other measures of memory and function.
About 21% of lecanemab-treated patients experienced brain swelling visible on PET scans, a side effect associated with drugs of this type. Less than 3% of those patients had symptomatic cases of swelling, the companies said.
The study, called CLARITY-AD, was the largest conducted to date to test the long-debated theory that removing toxic brain plaques, called amyloids, could slow the pace of Alzheimer’s disease by slowing the memory loss or delaying the onset of dementia.
Lecanemab is the first such treatment to support the so-called amyloid hypothesis in a large Phase 3 clinical trial after two decades of consistent failure and murkier results from similar experimental drugs.
“This is a statistically robust and positive study, but the treatment effect is small,” said Lon Schneider, a physician and Alzheimer’s disease expert at the University of California’s Keck School of Medicine. from South. Schneider warned that experts will have to take a closer look at the data on lecanemab when it is presented in more detail, but based on the results described in Eisai’s press release, he believes that lecanemab is likely to obtain Food and Drug Administration approval. Schneider did not participate in the study.
The FDA is already considering canemab for conditional approval, promising to make a decision by Jan. 6 based on preliminary evidence from a smaller study showing the drug’s effect on amyloid in patients’ brains. Eisai now plans to add the most definitive results from the CLARITY-AD study to its application, with the aim of obtaining full approval this summer and persuading Medicare to reverse a restrictive reimbursement policy established following ‘Aduhelm.
CLARITY-AD might be enough to convince the FDA, but the future of lecanemab depends on whether physicians, payers, and patients find the supporting data compelling. The study used a metric called the Clinical Rating of Dementia Sum of Boxes, or CDR-SB, which measures six cognitive domains, including memory, problem solving and self-care, and produces scores ranging from 0 to 18, with higher numbers indicating more severe dementia. .
In the 18-month trial, patients who received lecanemab performed 0.45 points better on the test than those who received placebo, a result that reached statistical significance, meaning it is unlikely to be the result of chance.
Aduhelm, in a comparable clinical trial, slowed the decline by 22%, outperforming placebo by 0.39 points on the same measure. A second identical study failed.
Lecanemab was administered as an intravenous infusion twice a month. Approximately 25% of the 1,800 participants in the CLARITY-AD study were Hispanic and African American, making it one of the most diverse populations ever enrolled in an Alzheimer’s disease clinical trial.
For lecanemab, statistical significance does not necessarily mean that it is a life-changing drug. Alzheimer’s disease researchers have spent years debating what small changes in CDR-SB scores mean for patients with the disease. Fractional improvement on an 18-point scale might be unnoticeable in real life. On the other hand, the metric is not an interval scale, which means that its numerical differences are not proportional to each other. Going from a 1 to a 1.5 on the CDR-SB could mean no longer being able to drive alone, while going from a 14 to a 14.5 would probably make little difference to a patient already plagued by dementia.
For Michael Greicius, a neurologist at Stanford University who studies and treats Alzheimer’s disease, the rate of brain swelling in the lecanemab study might be disconcerting. Once patients experience the common side effect, called an ARIA, everyone involved in the trial can be pretty sure they are getting the drug and not the placebo, exposing the study to bias. A true test of lecanemab’s benefits would be solely whether it helped patients who did not test positive for ARIA, Greicius said.
“I think if anything, it’s going to be on the cusp of what’s considered minimally clinically significant, and it may be below that,” said Greicius, who wasn’t involved in the study. “That’s where we need to see more data.”
Experts said any final decision on the value of lecanemab would require more detailed results from CLARITY-AD, which Eisai promised to present at a medical conference in November.
Wall Street had only moderate expectations for CLARITY-AD, with analysts pegging a low probability of success and saying even a marginal benefit would count as a plus for Biogen and Eisai. Biogen’s share price has fallen almost 50% since Aduhelm’s approval in 2021, and Eisai has lost around 60% of its value.
“Today’s announcement gives patients and their families hope that lecanemab, if approved, has the potential to slow the progression of Alzheimer’s disease and have a clinically meaningful impact on cognition and function,” Biogen CEO Michel Vounatsos said in a statement.
The results kick off what will be a transformational nine months for Alzheimer’s disease research. By the end of this year, Roche will have data from a pair of two-year studies of gantenerumab, another antibody that reduces brain plaques. And in the first half of 2023, Eli Lilly expects to have results from a Phase 3 trial of donanemab, a similar treatment that met its goals in a small study last year.