Eli Lilly recently announced that the FDA had granted a breakthrough therapy designation for donanemab, its investigational antibody therapy for Alzheimer’s disease. The designation means the FDA will expedite the drug’s development and review because it treats a serious condition, and early evidence has shown enough improvement on key clinical measures compared to other drugs on the market. This should mean it has a good chance of being effective in treating the condition.
Donanemab, also called N3pG, is an investigational antibody that targets a modified form of beta-amyloid, aiming to clear out plaques that have built up in the brain. Lilly’s Phase 2 trial, TRAILBLAZER-ALZ, studied the efficacy and safety of donanemab in patients with early, symptomatic Alzheimer’s. The results, which appeared in the May 6 New England Journal of Medicine, concluded that “donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed.”
Lilly plans to submit a biologics license application (BLA) for donanemab under the accelerated approval pathway later this year based on data from the trial, according to a statement from the company, which announced the FDA decision on June 24. The safety, tolerability and efficacy of donanemab also is being evaluated in an ongoing randomized, placebo-controlled, double-blind, multi-center Phase 3 study called TRAILBLAZER-ALZ 2.
For now, aducanumab (Aduhelm) is the only FDA-approved therapy to address amyloid plaque. However, the FDA is under fire for its contentious decision. A third member of the advisory panel who advised against approval has resigned. Cost and potential side effects remain serious concerns among many physicians and potential patients, as ethicist Leonard Fleck a professor of bioethics and social justice at Michigan State University, noted in an essay for The Hastings Center.
Fleck called on the company to provide the drug at cost, plus 5% profit. That would reduce the annual cost to approximately $2,500 to $5,000 while aducanumab undergoes the Phase 4 investigation. Fleck said it’s a reasonable tradeoff between reimbursement the uncertainty around the drug’s safety and efficacy. If the drug is proven viable in the trial, then perhaps the $56,000 price tag could then be justified given the “competing pressures of intense patient demand and just allocation of scarce health care resources.”
A recent poll from STAT found many Americans are excited about having a new drug to help treat the disease but expressed concern about how the FDA went about the approval process as well as the proposed price.
Will the FDA’s approval for aducanumab affect its decision-making on future Alzheimer’s drugs? Martin Tolar, the CEO of Alzheon, a biotech firm developing ALZ-801, which targets the APOE 4 gene to inhibit amyloid plaque formation, wasn’t sure. “They lowered the bar for approval for everybody else,” he said. He emphasized that his company’s data collection and analysis will be up to the highest scientific standards.
To learn more about the current treatment pipeline for Alzheimer’s disease, read part two of this package: Another Alzheimer’s treatment takes a different route than the rest