Lilly to appeal after CHMP rejects Alzheimer's drug Kisunla

The EMA's human medicines committee has said it does not recommend approval of Eli Lilly's anti-amyloid Alzheimer's disease treatment Kisunla, saying its modest benefits don't outweigh its risks.

The negative decision came even though Lilly proposed restricting the use of Kisunla (donanemab) to patients who do not have ApoE4, a gene variant for the protein apolipoprotein E that raises the risk of potentially serious amyloid-related imaging abnormalities (ARIA) with the drug, like brain bleeding and swelling.

As it stands, the decision puts Lilly at a disadvantage in the EU compared to rivals Eisai and Biogen, whose amyloid-targeting therapy Leqembi (lecanemab) has been recommended by the committee (the CHMP) for use in patients with only one or no copy of ApoE4, after being rejected earlier for use in a broader group of Alzheimer's patients.

Lilly said it is planning to request a re-examination of the CHMP's appraisal of Kisunla, pointing out that the drug has already been approved in the US, China, Japan, and other world markets for people with the early signs of Alzheimer's.

"Lilly remains confident in the safety and effectiveness of donanemab and the value it can bring to patients with early symptomatic Alzheimer's," said Lilly's International president, Ilya Yuffa.

The decision by the CHMP comes after Kisunla was approved for marketing in the UK, but immediately turned down for use by the NHS in England because the costs of providing Kisunla, including regular infusions and intensive monitoring for serious side effects, outweigh its relatively small benefit.

The EMA said that the CHMP's decision to take a tougher line with Kisunla stemmed in part from data in a small number of patients with no copies of the ApoE4 variant, which showed that even in this lower risk population the risk of ARIA was doubled to 24.7% of people who received Kisunla compared with 12% of those on placebo. While most cases were mild, there was an ARIA-related death in the Kisunla group.

"The benefits of Kisunla were not large enough to outweigh the risks of potentially fatal events due to ARIA, even in the small group of people who do not carry copies of ApoE4," said the agency.

In the US, both Leqembi and Kisunla are approved without the ApoE4 restriction, but with a black-box warning for ARIA risk.

Other CHMP decisions

At its March meeting, the CHMP also recommended approval of two other new medicines, Averoa's Xoanacyl (ferric citrate coordination complex) for the treatment of hyperphosphataemia and iron deficiency in adults with chronic kidney disease (CKD), and Santen's Ryjunea (atropine) for slowing the progression of myopia in children aged three to 14 years. There was also a positive opinion on Bristol Myers Squibb's new subcutaneous formulation of blockbuster cancer drug Opdivo (nivolumab).

Meanwhile, the CHMP also finished a review of the safety of Orexigen's weight-loss therapy Mysimba (naltrexone/bupropion), which concluded it should remain on the market, but with a 12-month time-limit on treatment duration if weight-loss of 5% isn't maintained. More information will have to be submitted to the EMA from an ongoing safety study, due to read out in 2028.