Alzheimer’s: the FDA does not approve the new drug and asks for an independent opinion

Alzheimer’s: the FDA does not approve the new drug and asks for an independent opinion

After past controversies, with an approved drug and a long list of external experts criticizing its effectiveness and safety, this time the American FDA is taking time and delaying the opinion on another Alzheimer’s drug, Eli Lilly’s donanemab, whose approval was expected this month. The agency instead decided to convene a panel of independent experts to evaluate the drug’s effectiveness and safety.

The decision surprised many experts who instead expected the drug to arrive on the market quickly, around the first quarter of this year. “We didn’t expect this,” said Anne White, Lilly’s executive vice president and president of the Neurosciences division. And that’s because she-she continued-while the FDA often convenes independent committees when it has questions about drugs, it is unusual for it to do so “at the end of a review process beyond the date communicated to us.”

The agency has made no public comment on the decision which will presumably postpone the approval of donanemab to the end of this year. Decision due precisely to precedents regarding other approvals for a disease, Alzheimer’s, which to date does not have a cure that can restore lost memory or cognitive decline. For years there have been promising drugs that later turned out to be useless. But donanemab, one infusion a month, belongs to a new class of drugs that experts hope could help patients fight the amyloid protein that forms plaques in patients’ brains.

Last year, the FDA approved another drug in the class, Leqembi, from Eisai and Biogen. An infusion every 15 days, Leqembi can modestly slow cognitive decline in the early stages of the disease.

The new drugs are considered only a first step because they cannot slow cognitive decline enough to be a visible result to patients and families, experts say. The drugs also pose significant health risks, including the dreaded brain swelling and bleeding. The first drug approved in the anti-amyloid class, Aduhelm, was challenged for weak evidence so much so that Biogen, the company that produced it, abandoned it.

Donanemab should easily win approval because data shows it can modestly slow cognitive decline in people with mild symptoms, and similar risk profiles to Leqembi. But the two drugs are not directly comparable because the donanemab study included some patients with more complex medical problems. The donanemab study has two unusual aspects that the FDA asked independent experts to evaluate, he said John Sims, Lilly’s medical director and head of studies on the drug. One feature is of interest to patients: Participants stopped receiving the donanemab infusion after their amyloid plaques had regressed to a certain level, which happened after about a year for half of the participants, and their cognitive decline slowed. Lilly doctors estimate that it takes about four years for amyloid levels to rise above the threshold again. According to Sims, the FDA wants to understand more on this point to evaluate whether other anti-amyloid drugs could be suspended at some point.

The other unusual feature of the study involves another protein, tau, which forms concentrations in the brain after amyloid buildups. Higher levels of tau are more closely associated with memory and thinking problems. The donanemab study divided participants into groups with high tau levels and intermediate levels. The latter people had slower cognitive decline, which supports the theory that treating patients as early as possible gives a better chance of slowing symptoms.

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