EU Regulators Reject Lilly's Alzheimer's Drug Kisunla, Raising Safety Concerns

The European Union's Committee for Medicinal Products for Human Use (CHMP) has issued a negative opinion on Eli Lilly's Alzheimer's drug Kisunla (donanemab), citing safety concerns that outweigh the potential benefits. This decision follows a similar path to that of rival drug Leqembi, developed by Biogen and Eisai, which initially faced rejection but later gained limited approval.

Safety Concerns Overshadow Potential Benefits

The CHMP's decision was primarily based on the risk of amyloid-related imaging abnormalities (ARIA), a side effect that can lead to potentially fatal brain swelling and bleeding. In clinical trials, 36.8% of patients taking Kisunla experienced ARIA, compared to 14.9% in the placebo group. While most cases were asymptomatic, 1.6% of patients suffered serious ARIA events, with three patients dying.

Eli Lilly reported modest improvements in Alzheimer's disease progression scores for patients taking Kisunla, both with and without the ApoE4 gene, a known risk factor for Alzheimer's. However, the CHMP determined that these benefits were not substantial enough to justify the associated risks.

Regulatory Challenges and Market Access

The rejection of Kisunla in Europe adds to the regulatory hurdles faced by Alzheimer's drugs targeting amyloid plaques. Leqembi, developed by Biogen and Eisai, initially received a negative opinion from CHMP in July 2024 but later secured a limited recommendation for patients with one or no copies of the ApoE4 gene. The European Commission subsequently requested a reevaluation based on new safety data, with CHMP reaffirming its positive stance earlier this month.

In the United States, both Kisunla and Leqembi have received FDA approval, albeit with black box warnings for ARIA risk. Kisunla was approved by the FDA in July 2024, while Leqembi gained approval earlier. However, uptake of both drugs has been slow as healthcare systems adapt to the new treatment paradigm.

Next Steps and Market Implications

Eli Lilly has announced its intention to seek a re-examination of the CHMP decision within the 15-day window provided. The company remains confident in Kisunla's safety and efficacy profile and hopes to continue discussions with European regulators to bring the drug to market.

Analysts from William Blair note that CHMP reversals occur in approximately 25% of re-examination cases, as seen with Leqembi. However, they caution that there is a "real risk" that Kisunla may not gain approval in the EU due to the high rates of ARIA reported in clinical trials.

The slow uptake of both Leqembi and Kisunla in the U.S. market is reflected in recent sales figures. According to Jefferies, Leqembi's U.S. sales were relatively flat at $18.9 million for the previous month, while Kisunla saw a modest increase from $3.2 million to $4.7 million in the same period.

As the landscape for Alzheimer's treatments continues to evolve, pharmaceutical companies face ongoing challenges in balancing efficacy with safety concerns, particularly in the European market. The outcome of Eli Lilly's re-examination request and any future regulatory decisions will likely have significant implications for the development and accessibility of amyloid-targeting Alzheimer's therapies worldwide.