Alzheimer’s drug from Eli Lilly wins backing of FDA committee

Much of the committee’s discussion focused on the safety of the drug, donanemab, which works by clearing a sticky plaque from the brain, amyloid beta, that is associated with the memory-robbing disease. In a clinical trial, three patients who received the drug died of a condition called ARIA that can cause the brain to bleed or swell, while there were no such deaths in a placebo group. There were also more deaths in the group that received the drug than in the placebo arm.

Still, the FDA signaled that it wasn’t overly alarmed by the drug’s safety profile, noting in a briefing document that the findings “are generally consistent” with the class of drugs that aim to reduce or eliminate amyloid plaques.

The committee voted 11-0 that donanemab was effective and that the benefits outweighed the risks for patients with mild cognitive impairment and mild dementia. Still, some committee members stressed the importance of educating health-care providers and patients, who may not all get the same benefit from the drug depending on the state of their disease and their genetics.

“I do believe we need to think responsibly if this medicine is going to come to market, because there are risks associated,” said Sarah Dean, the panel’s consumer representative.

The committee’s favorable recommendation, though not binding on the FDA, removes a hurdle to Eli Lilly winning regulatory approval. If approved, donanemab would be the third anti-amyloid drug since 2021 to win the FDA’s blessing after Aduhelm and Leqembi, both made by drugmakers Eisai and Biogen.

“We are pleased with the committee’s unanimous recognition of donanemab’s positive benefit-risk profile,” Mark Mintun, an Eli Lilly vice president, said in a statement. “We look forward to bringing this treatment option to patients.”

There remains an urgent need for additional treatments, according to the agency, for a disease that affects an estimated nearly 7 million Americans.

Eli Lilly shares rose 1.8 percent Monday, as panel members voted. Still, donanemab is unlikely to be an instant blockbuster, according to Wall Street analysts. David Risinger, an analyst at Leerink Partners, said in a research note Sunday that the drug has a “questionable competitive profile.”

A key feature of Eli Lilly’s approach is that treatment with the drug could be discontinued once a patient’s amyloid levels are reduced to a certain level. That assumes that dropping the treatment wouldn’t compromise the benefit of the drug that could reduce the treatment burden on patients. The FDA called this theory “reasonable” but not directly supported by evidence.

Leqembi has gotten off to a slower-than-expected start, with about 5,000 patients getting treatment in the United States, according to William Blair analysts. But its sponsors, Eisai and Biogen, are pursuing an injectable version that would be far more convenient for patients than the current infusion method, potentially giving it a leg up on donanemab if it wins approval. The two drugmakers said earlier this year that they would cease marketing Aduhelm, a controversial drug that fizzled commercially after conflicting results about its effectiveness.

Eli Lilly’s path hasn’t been entirely smooth. The drugmaker changed the primary measure of its clinical trial midcourse, drawing initial objections from the FDA that it appears to have ultimately overcome. In March, the agency surprised Lilly when it delayed making a decision on approving the drug and decided to hold an advisory committee meeting.

Monday’s meeting included emotional pleas from patients stricken with Alzheimer’s. One man appearing remotely by video described how, after an infusion of donanemab, “my right arm began to shake uncontrollably” and his blood pressure surged. Still, he concluded that the benefits outweigh the risks. “I’m pleased to tell you as a result of my treatment with the Lilly drug my amyloids have completely cleared,” he said.

Donanemab has its critics, including a few who argued against approving the drug during public comments at the meeting.

Judy Butler, senior research fellow at Georgetown University Medical Center, urged the committee to reject the medication, saying the medical terminology hides brain hemorrhaging behind the “benign acronym” ARIA.

“Just like its predecessors aducanumab and lecanemab” — alternative names for Aduhelm and Leqembi — “it does not improve how a patient feels, functions or survives,” she said of donanemab. “And the net effect of these drugs appears to be harm.”

Melissa Veenhuizen, vice president of global patient safety at Eli Lilly, told the panel that “there is no evidence of an increased risk of mortality or excess deaths related to donanemab” beyond the three deaths associated with ARIA. The trial reported outcomes for 853 patients who received donanemab and 874 who got a placebo. Also speaking on the company’s behalf, Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, called ARIA a “manageable adverse event.”

The donanemab studies offer additional proof that “if you get rid of the amyloid, people get a clinical benefit,” said Howard Fillit, co-founder of the Alzheimer’s Drug Discovery Foundation, which has received contributions from Eli Lilly and Biogen.

Still, Fillit noted that the existing treatments only modestly slow the disease and that future treatments must take different approaches. “There must be other mechanisms involved in the disease that we haven’t addressed,” he said.