The Food and Drug Administration has determined to delay motion on a intently watched Alzheimer’s drug, donanemab, which the company was extensively anticipated to approve this month. The F.D.A. will as a substitute require donanemab to endure the scrutiny of a panel of impartial specialists, the drug’s maker, Eli Lilly and Company, mentioned Friday.
“The F.D.A. has informed Lilly it wants to further understand topics related to evaluating the safety and efficacy of donanemab, including the safety results in donanemab-treated patients and the efficacy implications of the unique trial design,” the corporate mentioned in a press release.
The determination is prone to shock many Alzheimer’s specialists, medical doctors and sufferers who had anticipated the medicine would quickly be in the marketplace. The F.D.A.’s transfer was startling to the corporate, which had been planning for the company to greenlight the drug through the first quarter of this yr.
“We were not expecting this,” Anne White, an govt vp of Lilly and president of its neuroscience division, mentioned in an interview. She mentioned that whereas the F.D.A. typically calls on such impartial advisory committees when it has questions on medication, it was uncommon to take action “at the end of the review cycle and beyond the action date that the F.D.A. had given us.”
The F.D.A. didn’t say something publicly concerning the transfer, which is able to delay any determination about whether or not to approve donanemab till at the very least later this yr. Lilly officers mentioned they anticipated it will be just a few months earlier than the advisory committee holds a listening to.
“The F.D.A. did commit to us to move quickly, so we would hope that they would then take action shortly after the advisory committee,” Mrs. White mentioned.
The determination to convene an advisory committee displays the excessive stakes and rocky historical past of creating remedies for Alzheimer’s. The illness afflicts greater than six million Americans and at the moment has no remedy and no medicine that may restore reminiscence loss or reverse cognitive decline.
For years, the sector was marked by failed drug trials. But donanemab, an infusion given as soon as a month, belongs to a brand new class of medicine that specialists hope may assist sufferers by attacking a protein, amyloid, that clumps into plaques within the brains of individuals with Alzheimer’s.
Last yr, the F.D.A. authorized one other drug within the class, Leqembi, made by Eisai and Biogen. An infusion given each two weeks, Leqembi can modestly gradual cognitive decline within the early levels of Alzheimer’s.
The new medication are thought of solely a primary step in a doubtlessly fruitful path as a result of they might not gradual decline sufficient to be noticeable to sufferers or households, specialists say. The medication additionally carry important security dangers, together with swelling and bleeding within the mind.
(The first drug authorized within the anti-amyloid class, Aduhelm, was controversial as a result of it had weak proof; Biogen, the producer of the drug, lately deserted it.)
Donanemab was anticipated to win approval simply as a result of information confirmed that the drug may additionally modestly gradual cognitive decline in folks with delicate signs, and the protection dangers had been just like these of Leqembi. Because donanemab’s trial design was completely different than Leqembi’s and included some sufferers with extra complicated medical issues, the 2 medication’ trials can’t be straight in contrast.
Donanemab’s trial had two uncommon features that the F.D.A. indicated it will ask the advisory committee to guage, mentioned Dr. John Sims, a medical director with Lilly and the chief of the donanemab medical trials.
One function could be significantly interesting to sufferers: Participants within the trial stopped receiving donanemab after their amyloid plaques had been cleared to a sure stage — a couple of yr for half the individuals who began off with donanemab — and their cognitive decline stored slowing. Lilly scientists have estimated it will take almost 4 years for amyloid ranges to bump up over the brink once more.
Dr. Sims mentioned he believed the F.D.A. wished to know extra about stopping remedy as a result of “it’s very unique” and regulators may wish to discover whether or not different anti-amyloid medication could possibly be halted at a sure level.
Mrs. White mentioned that amongst medical doctors and sufferers, “there’s a lot of enthusiasm for this concept of once you clear the target that you’re going after, that you don’t need to put patients through additional infusions and visits.”
The different uncommon function of the trial concerned one other protein, tau, which types tangles within the mind after amyloid accumulates. Higher tau ranges are extra intently related to reminiscence and considering issues.
The donanemab trial divided individuals into teams with excessive tau ranges and intermediate tau ranges. People with intermediate tau ranges had extra slowing of cognitive decline — supporting a widespread principle that treating sufferers as early as doable within the illness course of supplies a greater probability of slowing signs.
Dr. Sims mentioned that measuring tau was “informative, but not necessary for instituting therapy for patients, and we had treatment effects across the entire spectrum of tau.” He mentioned that the F.D.A. had not indicated “the specifics of what they want to talk about” involving tau, simply that it was a topic the advisory committee would take into account.
Mrs. White mentioned, “There’s some people here at Lilly that have been working on this for 35 years, and so you can imagine that this was certainly a disappointment to them not to bring this to patients right now.” But she mentioned the corporate was assured in its information and would spend the following few months eager about “additional analyses that we can do to help answer any questions that someone might pose at us.”
