The Food and Drug Administration's approval of Biogen's Alzheimer's drug Aduhelm in early June has become one of the most controversial and publicly acrimonious decisions in the agency's recent history. In the nearly four months since, the decision has led to high-profile resignations by FDA advisers, a federal investigation and extraordinary pushback from a number of insurers and physicians.
Late on Monday evening, Japanese drugmaker Eisai, Biogen's partner in Alzheimer's research, revealed it had begun the process of asking the FDA for accelerated approval of a second drug that works similarly to Aduhelm. The application, which Eisai will file in a rolling fashion, was anticipated after Aduhelm's OK but comes months earlier than analysts expected it would be submitted.
In seeking approval, Eisai will test the precedent set by the FDA with Aduhelm and put the agency's decisionmaking under the microscope yet again. The pharma company is basing its application principally on results from a Phase 2 study that showed treatment with its drug reduced toxic brain plaques — an effect scientists have for decades hypothesized, but not proven, could slow Alzheimer's progression.
While that research remains unsettled, the FDA surprisingly cleared Aduhelm using data that indicated the drug could eliminate brain plaques, rather than looking solely at conflicting evidence from two large Phase 3 studies of whether that translated to patient benefit. The decision signaled acceptance of plaque lowering as an approvable effect, opening the door to companies with other drugs that did the same.
Eisai said it decided to use the accelerated approval pathway, and reduction in plaque as a surrogate marker, following discussions with the FDA, which it claimed had agreed to receive the drugmaker's application on a rolling basis. Only after Eisai finishes submitting the application will the FDA assign a target date for decision on approval.
Called lecanemab, Eisai's drug also has a checkered clinical trial history. In December 2017, one-year results from the Phase 2 study on which Eisai is basing its application showed the drug was unlikely to work. While the disclosure greatly dimmed expectations for lecanemab, testing continued for another six months. Unexpectedly, at that 18-month mark, Eisai said treatment with a high dose of the drug appeared beneficial.
Further data suggested a dose-dependent relationship between reductions in plaque and clinical benefit, as measured by an assessment created by Eisai along with two other, more standard Alzheimer's disease tests. But those data also raised new questions, leading some to doubt whether the drug was driving the positive findings as much as Eisai claimed.
In its Monday statement, Eisai did not say exactly which dose of lecanemab it's asking the FDA to approve, although it highlighted the 10 milligram per kilogram dose that delivered the best results in the Phase 2 trial. Three lower doses tested in that study didn't show any difference over placebo in slowing disease progression.
While Eisai began lecanemab's submission, the company splits development costs and any future profits from sales with Biogen under a partnership set up in 2014 and amended in 2017. Eisai licensed the drug a decade earlier from the Swedish company BioArctic.
Eisai and Biogen's collaboration on Aduhelm, which also dates to 2017, is structured differently, with Biogen leading development.
Like Aduhelm, lecanemab is designed to bind to and remove plaques from the brain, but at a different stage in their formation. Both drugs are meant to treat people early in their disease course, before Alzheimer's has too heavily damaged the brain and degraded cognitive function.
Eisai began a larger Phase 3 study of lecanemab in early Alzheimer's in March 2019 and completed enrollment earlier this year with 1,795 participants. The FDA, Eisai said, has agreed this study could serve as a confirmatory trial should the agency grant an accelerated approval. Results are due by September 2022, which, depending on when Eisai completes its application, could mean the company will have Phase 3 data before or around the time of a FDA decision. Drug reviews by the agency typically take 10 months after acceptance of an application.
Biogen's confirmatory study of Aduhelm, meanwhile, has yet to begin and could take up to nine years to deliver final results.
Other would-be Alzheimer's drugs could join Aduhelm on the market well before then. Eli Lilly has confirmed it will also seek a speedy approval of a plaque-busting therapy its developing called donanemab, and Roche is expected to advance a treatment of its own called gantenerumab.
Note: This story has been updated to include mention of the timing of data from Eisai's Phase 3 study.