The FDA issued a complete response letter on the accelerated approval of donanemab for treatment of early symptomatic Alzheimer’s disease, citing the limited number of patients with longer drug exposure data.

Manufacturer Eli Lilly said in a press release that the FDA specifically requested that the company provide data from at least 100 patients who received a minimum of 12 months of continued treatment with donanemab.

The accelerated approval application was based on phase 2 trial data, which demonstrated reduction of amyloid plaques in the brain, the company said. A phase 3 trial remains ongoing, with data expected in the second quarter of 2023.

Donanemab’s specificity to target deposited amyloid plaque informed the clinical trial design of the current phase 3 trial, which allowed patients to complete their course of treatment when they reached a predefined level of amyloid plaque clearance, according to Eli Lilly.

Although the phase 2 trial included more than 100 patients treated with donanemab, because of the speed of plaque reduction, many patients were able to stop treatment after 6 months, which resulted in less than 100 patients receiving 12 months of donanemab, according to Eli Lilly.

“We look forward to our upcoming confirmatory phase 3 results and subsequent FDA submission, which we’ve always seen as the most impactful next steps for patients,” Anne White, Lilly Neuroscience executive vice president and president, said in the release. “We anticipate this study will confirm the benefit and safety profile we observed in the phase 2 study and believe that patients and physicians will be well-served by having the full phase 3 data available alongside our phase 2 data when they need to make treatment decisions.”

The Alzheimer’s Drug Discovery Foundation (ADDF) issued a statement in response to the FDA’s request.

“This drug did what it was intended to do — remove amyloid plaques in the brain — and because of the trial’s innovative design, treatment was halted for patients once the biomarker PET scans confirmed the plaques were gone,” Howard Fillit, MD, co-founder and chief science officer at the foundation, said in an ADDF press release. “In some cases, this occurred in less than 12 months, which is why fewer patients stayed on the drug for a full year.”

The Alzheimer’s Association also responded, issuing a statement that it “appreciates” the FDA’s methodical process in reviewing treatments for AD.

“The FDA’s determination that additional data is required to reach a decision on accelerated approval of donanemab demonstrates the rigorous approach the agency takes in reviewing individual treatments,” the association said in a press release.

Earlier this month, the FDA authorized the accelerated approval of Leqembi (lecanemab-irmb, Eisai) for the treatment of AD. This was the agency’s second accelerated approval for an Alzheimer’s treatment, after it approved Aduhelm (aducanumab, Biogen/Eisai) in June 2021.

References:

ADDF statement on FDA decision not to grant accelerated approval to donanemab for treatment of Alzheimer’s disease. https://www.alzdiscovery.org/news-room/announcements/addf-statement-on-fda-decision-not-to-grant-accelerated-approval-to-donanemab-for-treatment-of-alzheimers-disease. Published Jan. 19, 2023. Accessed Jan. 20, 2023.

Alzheimer’s Association statement on FDA complete response letter for donanemab. https://www.alz.org/news/2023/donanemab-fda-complete-response-letter. Published Jan. 19, 2023. Accessed Jan. 20, 2023.