Eisai, Biogen's injectable Leqembi delayed as FDA asks for more data

What analysts viewed as a potential “inflection point” for Eisai and Biogen’s slow-footed Leqembi is facing a delay with the FDA.

That inflection point industry watchers have been waiting for is a more convenient injectable version of the two firms’ currently infused Alzheimer’s disease drug. But Eisai has been forced to delay filing of the subcutaneous formulation as the FDA is asking for more data that the company can’t immediately provide.

The FDA has required additional three-month immunogenicity data for subcutaneous Leqembi given at a maintenance dose of 360 mg weekly, Eisai and Biogen said Monday.

Eisai, which leads Leqembi efforts, first planned to start a rolling submission in March as it collects the additional data. But the FDA told the company that a fast-track designation for the under-the-skin formulation—separate from the infused version’s—is needed to enjoy rolling review. So Eisai had to first request that new designation, which the FDA will decide on within 60 days from the company’s March submission.

Leqembi’s launch has been slow so far because of its complicated logistics related to diagnosis and treatment. The antibody drug currently needs to be infused every two weeks, a requirement that poses a burden on the healthcare infrastructure and the patients. As establishing those practices takes longer than expected, Eisai earlier this year said Leqembi likely won’t meet the goal to reach 10,000 patients by the end of March.

Eisai and Biogen hope to alleviate the situation with less frequent infusions or a subcutaneous version. For the first part of that plan, Eisai on Monday filed with the FDA for approval of Leqembi as a monthly intravenous maintenance treatment after a biweekly-dosed initiation phase, the exact length of which remains under discussion with the FDA.

For the injectable version, the two companies had hoped that bioequivalence on pharmacokinetics and similar brain plaque reduction would suffice for an FDA application. However, the agency is now asking for more immunogenicity analyses. The partners have also been expecting a separate filing for the subcutaneous formulation as a full treatment, including the initiation phase, in 2025.

Back in October, data from an extension of the phase 3 Clarity AD trial showed that a subcutaneous injection of Leqembi cleared 14% more amyloid plaque in the brain of Leqembi-naïve patients at six months, although the rate of the side effect amyloid-related imaging abnormalities was slightly higher for the injectable.

The subcutaneous delay is a “technicality,” William Blair analysts said in a Monday note to clients. Still, this will push back a potential filing to the second half of 2024—or even longer if the FDA denies it the fast-track designation, the team noted.

In another recent setback, drug reviewers at the European Medicines Agency couldn’t discuss Leqembi’s application at a scheduled meeting last month because of “procedural reasons.”

“[T]hese are technicalities in our view and do not undermine the potential of Leqembi,” the William Blair analysts said, “but they are disappointing delays for Biogen, which clearly needs to demonstrate better execution to improve investor sentiment.”

At least Eisai and Biogen don’t have to worry about any immediate threat from a competitor. The FDA also postponed its ruling on Eli Lilly’ rival anti-beta-amyloid antibody donanemab. Rather than delivering a verdict by March, the FDA is now plotting an adivosry committee meeting to disuccss the Lilly drug’s data, and an exact date has not been provided.