Game on: Lilly's Alzheimer's drug Kisunla, a challenger to Biogen and Eisai's Leqembi, gains full FDA nod

After turning down Eli Lilly’s Alzheimer’s disease drug donanemab for an accelerated approval last year, the agency has now offered the anti-amyloid therapy—and a competitor to Eisai and Biogen’s Leqembi—a full approval.

The FDA has cleared donanemab-abzt, branded as Kisunla, to treat adults with early symptomatic Alzheimer’s disease, including people with mild cognitive impairment and those in the mild dementia stage of the neurodegenerative disease, Lilly said Tuesday.

Kisunla’s indication is almost identical to the FDA-approved use for Leqembi. Both drugs need confirmation of amyloid beta pathology in patients' brain tissue before beginning treatment, and both bear a boxed warning on the risk of amyloid-related imaging abnormalities (ARIA), which are known side effects of these antibodies that target the toxic aggregates of beta amyloid proteins.

But industry watchers believe Lilly’s offering holds at least one advantage, which the company was quick to highlight in its approval announcement. Kisunla is the first anti-amyloid drug that allows for stopping therapy when amyloid plaques are removed, enabling fewer infusions and lower treatment costs.

And while Leqembi is given as an intravenous infusion once every two weeks, Kisunla is dosed every four weeks. Lilly has priced Kisunla at a list price of $695.65 per vial. The total cost will depend on when a patient completes treatment. For one year, the Lilly therapy costs $32,000, which is higher than Leqembi’s U.S. launch price of $26,500 per year.

The disadvantage of Kisunla, however, is a perceived less favorable safety profile on ARIAs compared with Leqembi. And the drug's FDA label reflects this factor.

While Leqembi’s label requires four brain MRI scans before infusions, Kisunla’s demands five. The requirement for the extra MRI scan was expected after Lilly showed that an MRI prior to the second infusion led to a 25% reduction in serious ARIA cases.

In a June note to clients, Leerink Partners analysts said they expect Leqembi will grab more market share given its better ARIA profile, but the analysts also said the Alzheimer’s market is large enough for multiple players. Besides, the competitor launch should accelerate the uptake of the entire class by helping build the commercial infrastructure around the medicines, the team added.

In the TRAILBLAZER-ALZ 2 trial, patients who achieved a visually negative PET scan of amyloid plaques were able to complete their Kisunla treatment and switch over to placebo. At six months, 17% of people in the Kisunla group completed treatment. The number rose to 47% after one year, and 69% at 18 months. 

Even with that trial design, Kisunla significantly slowed the decline of cognition by 22% compared with placebo, as measured by the integrated Alzheimer's Disease Rating Scale (iADRS), over 18 months. The drug’s effect was more pronounced in those with milder disease, in whom the drug slowed the cognitive decline by 35%.

Lilly had previously tried to use amyloid plaque reduction results from the study to seek an accelerated approval, but the company received a rejection from the FDA at the beginning of 2023 because the agency had concerns about the limited number of patients who’d been on the drug for a year or more. Kisunla reduced amyloid plaques on average by 80% at 12 months and 84% at 18 months, compared to baseline measurements. 

Kisunla’s approval also comes at the end of a somewhat challenging regulatory path, with the FDA extending its review earlier this year to summon a council of outside experts to assess the amyloid-busting antibody. 

Ultimately, however, the advisory committee meeting for donanemab proved to be a boon for Lilly. Last month, the FDA’s outside experts voted unanimously in favor of Lilly’s drug on two voting questions around efficacy and safety.

Lilly's Kisunla arrives at somewhat of an opportune moment, given that Biogen and Eisai's Leqembi—and Aduhelm before it—have helped to clarify coverage Alzheimer's treatment pathways at the Centers for Medicare & Medicaid Services. 

Last summer, CMS blueprinted plans to broadly cover the new class of Alzheimer’s disease drugs that includes Kisunla and Leqembi once the therapies win full approval at the FDA. As part of the framework, the drugmakers behind the Alzheimer’s meds must enroll patients in real-world data collection registries to support the ongoing merit of their products.

CMS released the latest coverage decision after issuing a narrower coverage framework in 2022 for Leqembi's failed predecessor, Aduhelm. Under that coverage framework, CMS said new Alzheimer's antibodies approved under the FDA’s accelerated pathway would only be covered when administered in eligible clinical trials.

Not everyone was onboard with CMS’ new approach last year, including the industry trade group PhRMA, which cautioned that the registry framework could “severely restrict” patient access and raise barriers to “potentially life-changing” treatments.