A drug Eli Lilly expected to win approval as a treatment for Alzheimer’s disease has been put on hold pending further review. In a surprise move, the U.S. Food and Drug Administration announced plans to have an advisory committee look at the safety and efficacy of donanemab before it decides whether the drug can be marketed to treat the degenerative brain disorder.
Donanemab targets amyloid beta plaques in the brain, which are believed to be a key component of Alzheimer’s. The disease impacts at least 6 million Americans.
Per The Washington Post, “The call for additional scrutiny surprised Lilly executives, who noted that it is unusual for such a review to occur after the FDA has given an anticipated date to make a decision on approval.”
Instead, the FDA said it will gather together its Peripheral and Central Nervous System Drugs Advisory Committee to discuss findings of the phase 3 clinical trial, which looked at how well donanemab works in early symptomatic Alzheimer’s disease. When that will happen, though, is not known.
The Alzheimer’s Association issued a statement calling for a swift review and decision. “While the decision is a surprise at this stage in the review process, the safety and appropriate administration of treatments is paramount,” the group said. “On behalf of everyone who could benefit from this treatment, we strongly urge the FDA to move swiftly in this next stage of its review.”
“We are confident in donanemab’s potential to offer very meaningful benefits to people with early symptomatic Alzheimer’s disease,” Anne White, executive vice president of Eli Lilly and Company and president of Lilly Neuroscience, said in a written statement. “It was unexpected to learn the FDA will convene an advisory committee at this stage in the review process. … We will work with the FDA and the stakeholders in the community to make that presentation and answer all questions.”
The company said that the 1,736 participants from eight countries in its phase 3 study were chosen based on cognitive assessments in conjunction with amyloid plaque imaging” and the presence of tau tangles, both seen using positron emission tomography (PET) imaging. Compared to other trials using therapy targeting amyloid beta, these trial participants had more advanced disease. And all of them benefited from donanemab, per Eli Lilly, “with the patients in earlier stages of the disease experiencing the stronger results.” The company also noted that about half of the participants completed their course of treatment in six to 12 months.
But they did note a potentially life-threatening side effect, called “amyloid related imaging abnormalities,” including brain swelling and tiny hemorrhages. More common risks include reaction to the infusion, headache and nausea.
Alzheimer’s drug controversy
The results of the phase 3 trial were published in the Journal of the American Medical Association. Study of the drug, in different clinical trials, is ongoing.
Donanemab was earlier denied fast-track approval by the FDA, which asked that more data be collected in clinical trial. Two other drugs that also target amyloid beta won previous, but contentious, approval. Aduhelm, in the words of the Post, “sputtered commercially after Medicare declined to broadly reimburse for it.” It was already controversial because the FDA approved it against the advice of its advisory panel. Biogen stopped marketing the drug this year. The other drug produced by Biogen and Eisai, Leqembi, did win approval and Medicare — after a great deal of pushback on an earlier decision to deny coverage — said it would cover that drug. But Leqembi also had adverse events in some trial participants, including brain bleeds. And uptake of the drug is reportedly lower than expected, with some experts suggesting cost and the proof-of-disease required, including scans, is likely slowing down use.
Drugs targeting amyloid beta plaques appear to slow the disease, but don’t reverse it, experts say. That’s why they have thus far been approved for early-stage Alzheimer’s disease.
According to CNN, the phase 3 clinical trial had a “unique trial design,” grouping people by the levels of an Alzheimer’s-related protein called tau, which is believed to interact with the amyloid beta and the decision that once amyloid beta cleared from the brain, the participants could stop taking donanemab. The study said that for participants with an “intermediate level” of tau, those on donanemab had 35% slower decline in thinking and ability to do daily tasks, compared to folks on placebo.
“When people with high levels of tau — who are thought to be further along in the disease — were included, the benefit compared to placebo was 22%,” per CNN.