The FDA today approved Eli Lilly’s early Alzheimer’s disease drug Kisunla™ (donanemab-azbt), a once-monthly injection treatment indicated for adults with early symptomatic Alzheimer’s disease (AD), including mild cognitive impairment (MCI) or mild dementia stage of disease with confirmed amyloid pathology.

Kisunla is the first amyloid plaque-targeting therapy with evidence to support stopping therapy when amyloid plaques are removed, which according to Lilly can reduce both the number of infusions needed as well as the treatment cost.

The FDA based its approval of Kisunla on positive data from the Phase III TRAILBLAZER-ALZ 2 trial (NCT04437511), in which people least advanced in the disease showed the strongest results 18 months after receiving the drug. Treatment with Kisunla significantly slowed clinical decline in two groups: Patients with low to medium levels of tau protein, and patients mirroring the overall population, which also included participants with high tau levels.

According to Lilly, patients treated with Kisunla who were less advanced in their disease showed a significant slowing of decline of 35% compared with placebo on the integrated Alzheimer’s Disease Rating Scale (iADRS), which measures memory, thinking, and daily functioning. In the overall population, a statistically significant 22% showed response to treatment based on the iADRS.

Among the two groups analyzed, participants treated with Kisunla had up to a 39% lower risk of progressing to the next clinical stage of disease compared with placebo patients. And among patients in the group mirroring the overall population, Kisunla reduced amyloid plaques on average by 61% at six months, 80% at 12 months, and 84% at 18 months compared to the start of the study.

“Very meaningful results”

“Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer’s disease, who urgently need effective treatment options. We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis,” Anne White, executive vice president and president of Lilly Neuroscience, said in a statement.

The positive data led to a recommendation in favor of the drug last month by the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee. Through two 11–0 votes, the advisory panel unanimously concluded that it was effective in treating patients with mild cognitive impairment, based on available data—and that the benefits of the drug outweighed its risks.

Lilly had been pursuing FDA approval for Kisunla since July 2022. The pharma giant initially expected a decision in the first quarter of this year, only to be told in May the agency would decide after hearing from the advisory committee.

Akash Tewari, an equity analyst with Jefferies, has projected peak annual sales for Kisunla of $2.9 billion—below the $4.6 billion projected by a consensus of analysts, asserting that Leqembi has shown an incrementally better risk-benefit profile in early AD patients. Tewari expects a commercial launch for Kisunla in the fourth quarter of this year.

Lilly has set a list price of $695.65 per vial for Kisunla, or about $32,000 for a year of treatment. That’s about 21% above the $26,500 annual list price in patients of typical weight for Leqembi® (lecanumab-irmb), an Alzheimer’s treatment marketed by Eisai and Biogen which gained full approval four days short of a year ago (Leqembi received accelerated approval in January 2023). The costs for patients needing six and 18 months of treatment have been set at, respectively, $12,522 and $48,696.

“Duration of Kisunla regimen will differ across pts [patients],” Tewari wrote in a research note, “so we’ll need to see how real-world data w/ Kisunla looks.” He noted that the average time to negative amyloid beta level was ~47 weeks in the TRAILBLAZER-ALZ2 trial.

Alzheimer’s has been a notoriously difficult indication for drug developers. Only a handful of drug successes have ever reached the market, most of which have merely slowed progression of symptoms by six to twelve months.

2014 Cleveland Clinic study found a 99.6% failure rate of clinical trials for AD drug candidates between 2002 and 2012. That study found high attrition rates for AD treatments, with 72% of agents failing in Phase I, 92% failing in Phase II, and 98% failing in Phase III.

Reshaping AD drug landscape

Kisunla is also the second new drug in as many years that is expected to reshape the AD drug landscape following decades of failures by big pharmas and small biotechs alike. The other is Leqembi, a recombinant humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody designed to treat Alzheimer’s by targeting aggregated soluble and insoluble forms of amyloid beta (Aβ).

The FDA is reviewing Eisai’s Supplemental Biologics License Application (sBLA) for a monthly intravenous maintenance dosing form of Leqembi, with the agency setting a Prescription Drug User Fee Act (PDUFA) target action date of January 25, 2025.

Leqembi is one of two amyloid-targeting Alzheimer’s drugs from Eisai and Biogen to win FDA approval in recent years. The other is Aduhelm® (aducanumab-avwa), which won a controversial but historic FDA accelerated approval in 2021 as the first therapy indicated for reducing clinical decline in AD patients and the first therapy to tie improved clinical outcomes to removing amyloid beta. Aduhelm became the first treatment approved with an Alzheimer’s indication since 2003.

However, in January Biogen ended commercialization of Aduhelm following disappointing sales and the failure of the drug to gain reimbursement from the Centers and Medicaid and Medicare Services. The latter triggered Biogen’s initial rounds of cost-cutting in 2022, as well as the departure of the company’s previous CEO Michel Vounatsos, since succeeded by current CEO Christopher Viehbacher. Biogen said it would instead shift resources to commercialization of Leqembi and development of other pipeline candidates designed to treat Alzheimer’s.

The disruption caused by Aduhelm, Leqembi and now Kisunla has fueled development of new Alzheimer’s therapies by other biopharma giants, and several smaller biotechs—including Alzheon, which last month completed a $100 million Series E financing, and Cognition Therapeutics, which has shown clinical success for its lead candidate CT1812.

Howard Fillit, MD, co-founder and chief science officer for the Alzheimer’s Drug Discovery Foundation (ADDF), hailed the FDA approval of Kisunla.

“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,” Fillit stated. “This approval is emblematic of the new era of Alzheimer’s research where we now have the first class of disease-modifying drugs that will eventually be used in combination with novel therapies—based on the biology of aging—that target all the underlying complexities of this disease.”

“This milestone will not only catalyze the next generation of therapies, but also reframe how we deliver treatments,” Fillit added.

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