“I agree with the FDA decision today regarding approval,” said R. Scott Turner, director of the Memory Disorders Program at Georgetown University, after the agency cleared Eli Lilly’s donanemab. The drug is a once-monthly 350 mg/20 mL infusion, sold as Kisunla, for adults with early symptomatic Alzheimer disease. Turner told NeurologyLive that its efficacy and safety are proven for people with mild cognitive impairment or mild dementia due to the disease.
Patients must have confirmed amyloid pathology to receive it.
Where it sits among amyloid drugs
Donanemab is the third antiamyloid therapy to win FDA approval. Aducanumab (Aduhelm, from Biogen) got conditional approval in 2021 and was withdrawn from the market earlier this year. Lecanemab (Leqembi, from Eisai) followed in 2023. Patients with early-stage disease now have donanemab and lecanemab to choose from.
One feature sets Kisunla apart. It is the first and only medication with evidence supporting a stop to treatment once amyloid plaques are cleared, which could mean fewer infusions and lower therapy costs. Howard Fillit, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said he is encouraged by that potential to stop, which could cut out-of-pocket costs and the infusion burden.
Turner pointed to the next open question: Medicare and other payers have yet to decide on coverage. If they cover it, he said, clinicians and eligible patients will get a choice between lecanemab and donanemab. He added that a more competitive market “may also lead to price competition”.
What the trial showed
The approval came less than a month after a positive recommendation from the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee. It rests on TRAILBLAZER-ALZ-2, a phase 3, double-blind, placebo-controlled trial of 1736 patients with early-stage Alzheimer disease. Some 860 received donanemab and 876 received placebo, every 4 weeks for up to 72 weeks, at 277 medical sites in 8 countries.
In patients with low or medium tau pathology, the iADRS score changed by -6.02 on donanemab and -9.27 on placebo at 76 weeks. That works out to a 35.1% slowing of disease progression. In the overall population the effect was smaller, a 22.3% slowing. Patients in the low and medium tau group also had a 38.6% lower risk of moving to the next clinical stage on CDR-Global. By week 76, 80.1% of them had cleared amyloid; no one on placebo had.
Safety looked like earlier findings and matched what is seen across amyloid-lowering drugs. ARIA-E, a type of amyloid-related imaging abnormality, occurred in 24% of patients, and most events were mild to moderate on imaging. They usually appeared within the first three infusions (58%). The first events resolved on imaging in 98% of participants, in a mean of about 10 weeks. Recurrent ARIA-E hit 6% of patients on active treatment.
A separate head-to-head trial, TRAILBLAZER-ALZ-4, compared donanemab with aducanumab. After 6 months, 37.9% of donanemab patients had cleared amyloid versus 1.6% on aducanumab.
Anne White, executive vice president of Lilly and president of Lilly Neuroscience, said in a statement that Kisunla “demonstrated very meaningful results” and that the medicines work best when patients are treated earlier in the disease.
