Lilly, citing FDA feedback, won't seek speedy approval of Alzheimer's drug

 

• An Eli Lilly executive said on a conference call Tuesday that the company won't seek an accelerated U.S. review of its experimental Alzheimer's disease drug donanemab based on Phase 2 data the company disclosed last month.
• Lilly is still in discussions with the Food and Drug Administration and is "fully exploring any opportunities for early submissions," said chief scientific officer Dan Skovronsky. But in the meantime, the company announced plans to start a new donanemab study in presymptomatic Alzheimer's patients. That trial will begin later this year and should take a year to fully enroll. Disease progression will be measured after three years, Skovronsky said.
• Winning an early approval of an Alzheimer's drug based on mid-stage data is unlikely "based on feedback from the FDA," he said. Nonetheless, interest has grown because of the FDA's unusually friendly stance toward Biogen's experimental drug aducanumab. That could change, however, should the regulator reject it by a review deadline of June 7.

Drugs that target the accumulation of a protein called amyloid in the brains of Alzheimer's patients have a long history of showing promise in early trials before falling short in larger Phase 3 tests. Until Biogen's aducanumab, no drug been shown to significantly delay disease progression — and many have argued Biogen failed on that measure as well given controversial and conflicting data. 

Eli Lilly, which had its own disappointing and expensive setback with an drug called solanezumab, is optimistic donanemab might be different based on the findings from the TRAILBLAZER-ALZ study. In the Phase 2 trial, patients who took donanemab experienced disease progression, as measured by a scale that tests function and cognition, that was one-third slower than those who received a placebo.

The results were from a small group of just 257 patients. But they were persuasive enough for Lilly to alter its clinical plan for the drug, which involved enlarging a study called TRAILBLAZER-ALZ 2 and designating it as a Phase 3 trial intended to support FDA approval. At the time, the company wanted to explore the possibility of gaining accelerated approval — a tool the FDA uses for drugs that treat serious diseases where no or few other options exist — based on TRAILBLAZER-ALZ 1. That option now appears off the table.

"We currently do not see a path forward for near-term submission and approval based on the first TRAILBLAZER-ALZ study alone," Skovronsky said on the conference call Tuesday.

Testing in presymptomatic patients is likewise a high-risk strategy, but also one with a big payoff if Lilly succeeds. The setting is also one Lilly is well familiar with. Its once highly touted Alzheimer's antibody solanezumab fell short in a study, DIAN-TU, testing the drug in presymptomatic patients.

Lilly hasn't been deterred, however. Skovronsky said because amyloid accumulates in the brain for years before patients show symptoms, treating people earlier could have a greater effect on slowing disease progression. And it's possible to do so now because of improvements in diagnostic technology. Potential enrollees can be identified with blood tests rather than expensive brain scans.

"That's a huge advance that just unlocks this trial," he said.

https://www.biopharmadive.com/news/lilly-donanemab-fda-accelerated-review-alzheimers/599118/