Eli Lilly Alzheimer’s disease drug has received its long-awaited FDA approval, bringing patients a treatment that works similarly to an Eisai medication for the neurodegenerative disorder but with dosing advantages that patients might prefer.
The Tuesday regulatory decision comes less than a month after an FDA advisory committee voted unanimously that the benefits of the Lilly drug in slowing cognitive decline outweigh its safety risks. The approval covers the treatment of Alzheimer’s patients with mild cognitive impairment or mild dementia, the same population that was evaluated in clinical trials. Known in development as donanemab, Lilly will market its new Alzheimer’s medication under the brand name Kisunla.
One of the hallmark characteristics of Alzheimer’s is the aggregation of two types of protein in the brain: amyloid beta and tau. Kisunla is an antibody designed to target and reduce plaques of amyloid beta protein in the brain. Lilly supported its FDA submission with data from a placebo-controlled Phase 3 study that enrolled 1,736 patients with confirmed amyloid plaques and mild cognitive impairment or mild dementia due to Alzheimer’s. The main study goal was to measure the change in score according to a rating scale used to assess Alzheimer’s patients.
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Over 18 months, the study drug arm evaluated two groups of patients: one with low-to-medium levels of tau and an overall population of patients with high levels of that protein. Results showed that the group with low-to-medium tau achieved a statistically significant 35% slowing of decline compared to placebo, as measured by a rating scale used to assess cognitive and functional ability in Alzheimer’s patients. That translates to about a six month delay in reaching the same level of cognitive and functional decline compared to a placebo. In the overall study population, the slowing of decline was 22%. These results were also statistically significant. Furthermore, data from the study showed that Kisunla-treated patients had a 39% lower risk of progressing to the next stage of disease compared to those who received a placebo. The study results were published last year in the journal JAMA Network.
One of the secondary goals of the clinical trial was to measure clearance of amyloid from the brain. In the overall study population, medical imaging of brains showed treatment with Kisunla reduced amyloid plaques from baseline by an average of 61% at six months, by 80% at 12 months, and by 84% at 18 months. Patients confirmed to have reached specified levels of amyloid clearance were permitted to stop taking the drug and receive a placebo for the remainder of the trial. This unusual trial design played a role in regulatory setbacks that delayed an FDA decision for the drug.
In early 2023, the FDA turned down Lilly’s application, asking for more data from patients who took the drug for at least 12 months. At the time, Lilly did not have those data because the amyloid clearance achieved by Kisunla meant many patients were moving off of the study drug before hitting the 12-month mark. Lilly eventually gathered the requested data and resubmitted its application last summer. But this past March, the FDA told Lilly it would convene an advisory panel to weigh in on the drug, a move that was consistent with the reviews of Aduhelm and Leqembi, the antibody drugs from partners Biogen and Eisai that had each received accelerated FDA approval. While this additional layer of review further delayed the regulatory decision, the approval was welcomed by the Alzheimer’s community.
“This milestone will not only catalyze the next generation of therapies, but also reframe how we deliver treatments,” Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said in a prepared statement. “It’s promising to see that some patients essentially enter remission, where they achieve full amyloid clearance with no resurgence in substantial plaque buildup for several years to follow.”
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Kisunla’s label carries a black box warning that alerts clinicians and patients about the risk of serious and potentially life-threatening brain bleeds and inflammation. The label also cautions that people who carry the ApoE 4 gene have a higher risk of developing these complications. These risks are associated with the class of antibody drugs for Alzheimer’s. The black box warning for Leqembi is similar.
While Biogen has stopped selling Aduhelm, Eisai leads the commercialization of Leqembi and is continuing to market that product. Leqembi, which received full FDA approval last July, is administered as an hourlong intravenous infusion every two weeks. By contrast, Lilly’s Kisunla is given as a 30-minute infusion administered once monthly.
Leqembi carries an annual price of $26,500, but comparing pricing with Kisunla is tricky. Lilly has priced its new Alzheimer’s drug at $695.65 per vial, and like Leqembi, the number of vials needed is calculated according to a patient’s weight. But complicating the pricing picture is the dosing schedule. Unlike Leqembi, which patients will take indefinitely or until adverse effects warrant stopping treatment, the Lilly drug’s label permits stopping treatment after medical imaging shows removal of amyloid plaques — just as it did in its Phase 3 clinical trial. That means for some patients, a shorter duration of treatment is possible. Less frequent dosing and the possibility of stopping dosing entirely reduces a patient’s exposure to the therapy, which in turn lowers the safety risk to the patient.
Lilly provided several examples of treatment scenarios for its new drug. A patient needing 12 months of treatment with Kisunla would require 13 infusions for a total cost of $32,000, making it more expensive than one year of Leqembi. Six months of treatment would require six infusions totaling $12,522, while 18 months of treatment would require 19 doses at a total cost of $48,696. The out-of-pocket cost to patients will depend on the duration of treatment and the patient’s insurance. A Centers for Medicare and Medicaid Services coverage determination established for Aduhelm in 2022 covers the entire class of amyloid plaque-busting antibody drugs, including Kisunla.
[Story updated to add the following two paragraphs with analyst comments.] In a note sent to investors on Wednesday, William Blair analyst Myles Minter wrote that while Kisunla has an apparent dosing advantage, Eisai can counter with a once-weekly subcutaneous injection version of Leqembi currently under regulatory review. This new formulation could launch in 2025. Acknowledging all of the caveats with cross-trial comparisons, Minter noted that the rates of brain complications in the Kisunla trial were roughly double the rates reported for Leqembi. He expects debate over whether to select Leqembi as an option for traditional chronic therapy or Kisunla for the potential option of stopping therapy if plaque removal is achieved. Still, with more than 6 million Alzheimer’s disease patients in the U.S. alone, Minter sees room in the market for both therapies.
“Moreover, we continue to believe a second approval strengthens patient, provider, and payer confidence in anti-amyloid antibody efficacy following the Aduhelm collapse,” he said. “With Biogen and Eisai recently expanding the U.S. Leqembi sales team, we believe Eli Lilly entering the market will only boost awareness, overall demand, and hopefully aid in clearing some of the patient bottlenecks in scheduling neurologist visits and required imaging to get on to anti-amyloid therapy early in the disease course.”
Photo: Craig F. Walker/The Boston Globe, via Getty Images