Dive Brief:

• The Food and Drug Administration is delaying an approval decision on Eli Lilly’s experimental medicine for Alzheimer’s disease so it can hold an advisory committee meeting to more closely scrutinize the drug’s safety and effectiveness, the company said Friday. 
• According to Lilly, the FDA wants more input on the “unique” design of the key study underlying the company’s approval application, which allowed enrollees to stop taking the drug, donanemab, once it cleared clumps of amyloid protein from their brains. The agency also seeks more information on the safety of donanemab, which, like other, similar Alzheimer’s drugs, is associated with a type of brain swelling. 
• Lilly has been expecting a verdict on donanemab by the end of March. An advisory committee meeting will push a decision date past the first quarter, the company said. 

Dive Insight:

After decades of disappointments, two drugs designed to slow the progression of Alzheimer’s disease have been approved in the last three years. Both have struggled to gain traction, though. One, Biogen’s Aduhelm, was pulled from the market because of low sales and limited effectiveness. The other, Eisai and Biogen’s Leqembi, has had a slower-than-expected start, with about 2,000 U.S. patients receiving it as of mid-February.

The surprise delay for donanemab gives Eisai and Biogen more time to establish Leqembi ahead of what could be tough competition from Lilly. While the two drugs haven’t been formally tested against one another, making comparisons difficult, donanemab had a more pronounced impact on disease progression than Leqembi in clinical testing. Donanemab also removed amyloid plaques so well that more than half of those who received it discontinued treatment, which, in real-world use, could reduce the risk of adverse events.

Lilly acknowledged that it is “unusual” for the FDA to schedule an advisory committee meeting so late in a drug’s evaluation. An advisory panel also adds more risk to an FDA review, as a negative vote can influence the regulator’s stance. Still, Lilly noted that the agency similarly called on outside advisers to review Aduhelm and Leqembi and approved both afterward.  

A prominent patient advocacy group also argued that the FDA’s decision to call the panel is part of normal regulatory review. 

“Today’s FDA decision is not a setback, but another step forward in the drug approval process, with the regulatory agency doing its due diligence before the distribution of the drug to patients,” said Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation.

Nonetheless, it’s another delay for donanemab. The FDA last year turned back Lilly’s attempt to win an accelerated approval based on the results of a Phase 2 trial. Data from the more recent study, a Phase 3 trial called TRAILBLAZER-ALZ 2, were revealed four months later. In that study, patients taking donanemab declined about 35% slower than those taking a placebo.