In a move that surprised many, the Food and Drug Administration has rejected Eli Lilly’s application for accelerated approval for its anti-amyloid antibody donanemab. The agency said there was not enough safety data, given that fewer than 100 people in the Phase 2 trial stayed on drug for one year. “No other deficiencies were identified,” Lilly noted in a January 19 press release. The company said its Phase 3 Trailblazer-Alz2 study remains on track to read out in June. If the results are positive, Eli Lilly will apply for traditional approval.
Unlike some previous FDA decisions, the news stirred up no strong feelings, with many saying the decision will have little impact on donanemab’s development. “I do not think this has any implications for the overall program involving these drugs,” Ron Petersen at the Mayo Clinic in Rochester, Minnesota, told Alzforum. Industry analysts agreed, noting that because the Centers for Medicare and Medicaid Services do not cover amyloid immunotherapy, an accelerated approval would have resulted in little clinical use (Endpoint news).
Some praised the FDA’s measured approach. “I think the FDA made a thoughtful decision,” said Eric Reiman at the Banner Alzheimer’s Institute in Phoenix.
Lilly’s application for accelerated approval rested on Phase 2 data from Trailblazer-Alz1. In this 18-month study, 131 people started out on donanemab, but dosing was stopped once participants became amyloid-negative. This was defined as below 11 centiloids on one PET scan, or below 25 on two consecutive scans, which were done at six, 12, and 18 months. At six months, 40 percent of the cohort, or 52 people, were switched to placebo, leaving only 79 participants continuing on donanemab to one year (Mar 2021 news).
The 100-person stricture is unlikely to affect an approval based on Phase 3 data. Trailblazer-Alz2 enrolled more than 1,800 participants, according to Dawn Brooks at Eli Lilly. If a similar proportion as in Phase 2 stop treatment at six months, around 540 people would complete at least a year of treatment. “Lilly has collected sufficient 12-month exposures during Lilly’s ongoing Phase 3 Trailblazer-Alz 2 study,” Brooks wrote to Alzforum.
Eric Siemers of Siemers Integration LLC summed up the collective view. “At this point, the field just anxiously awaits the Phase 3 results for donanemab,” he wrote to Alzforum.—Madolyn Bowman Rogers
- Donanemab Mops Up Plaque Faster Than Aduhelm
- In TRAILBLAZER, Plasma GFAP Falls, but NfL Continues to Rise
- Drilling Down into the CMS Aduhelm Decision—A Primer
- On Donanemab, Plaques Plummet. Off Donanemab, They Stay Away
- Donanemab Phase 3 Puts Plasma p-Tau, Remote Assessments to the Test
- Can Donanemab Prevent AD? Phase 3 TRAILBLAZER-ALZ3 Aims to Find Out
- In Phase 2, Donanemab Curbs Cognitive Decline in Early Alzheimer’s