In an unusual reversal, key drug regulators in Europe are now saying Leqembi, a high-profile medicine for Alzheimer’s disease, should be approved there, though only for patients less likely to experience a certain kind of concerning side effect.
Leqembi’s primary developer, Japan-based Eisai, submitted a marketing application to the European Medicines Agency in early 2023. After some delays, the agency concluded this summer that the drug’s safety risks outweigh its potential benefits. Chief among those risks was the “frequent occurrence” of a side effect known as “ARIA,” which can present as brain swelling and small-scale bleeding.
Eisai appealed the EMA’s so-called negative opinion. The appeal process takes about four months and assigns different reviewers to assess the application. It’s also rarely successful for drug developers. Analysts at the investment firm RBC Capital Markets crunched the numbers and found that, over the past decade, the EMA’s main drug review committee has changed its mind only 20% of the time.
But Leqembi beat the odds. The committee said Thursday it supports approval for patients with mild cognitive impairment or mild dementia due to Alzheimer’s, who have one or no copies of a gene believed to increase the risk of ARIA. According to Jefferies analyst Michael Yee, around 60% to 80% of the Alzheimer’s population in Europe fits that genetic profile. Yee also noted that Leqembi seems more effective in this type of patient, which may therefore help justify its price and reimbursement to European payers.
However, the recommendation also comes with a caveat that measures be in place to reduce the risk of severe and symptomatic ARIA and “monitor its consequences in the long term.” The committee’s new opinion will be sent to the European Commission, which makes the ultimate verdict on what drugs receive marketing authorization in the EU.
“On one hand, we believe the single-payer healthcare systems in Europe could enable fewer bureaucratic hurdles than were faced in the U.S. around screening, drug administration, and monitoring, which could enable smoother ultimate uptake,” wrote RBC analyst Brian Abrahams in a note to clients Thursday. Even so, “there may be time lags and uncertainty on reimbursement,” and the drug’s price will likely be lower than its U.S. tag of roughly $11,000 per patient.
“Although Leqembi’s entrance into the EU market is an overall positive, we expect [Biogen] and Eisai to face commercial hurdles similar to the U.S., which has led to relatively tepid uptake dynamics so far,” wrote Piper Sandler analyst Christopher Raymond in his own note to clients.
A sign outside Biogen’s Cambridge, Massachusetts, offices shows the company’s logo on Sept. 5, 2024.
Jacob Bell/BioPharma Dive
Eisai and its partner Biogen work together commercializing Leqembi, and initially hoped European regulators would clear the drug for a broader group of Alzheimer’s patients. Yet, even a narrower approval could significantly boost sales. Abrahams has estimated that peak annual Leqembi sales would reach $8.3 billion, with 20% coming from the European market.
Eisai recorded 10 billion yen, or about $66 million, in Leqembi revenue between July and September. Biogen said the drug’s improving sales are one reason the company expects to do better on a key metric of financial health this year.
Leqembi is designed to combat Alzheimer’s by breaking up clumps of toxic proteins. These “amyloid beta” proteins have long been seen as a root cause of the disease, making them a prime target for pharmaceutical researchers. Kisunla, a recently approved product from Eli Lilly, also works on amyloid beta, as does another medicine from the Eisai and Biogen partnership, Aduhelm, though that drug was shelved following a series of commercial setbacks.
In making its decision, the EMA’s committee pointed to clinical data showing the differences in ARIA rates among participants who had one or no copies of that risk gene, and those with two. In that former group, nearly 9% and 13% of those who got Leqembi experienced brain swelling and microbleeding, respectively, while the rates among those who got a placebo were 1.3% and 6.8%.
Among all the participants who got Leqembi, the rates of ARIA brain swelling and microbleeding were 12.6% and 16.9%.
As for effectiveness, the committee said the “benefits of Leqembi in the restricted population are in line with those seen in the broader population.” Regulators in the U.S., Japan, China and a handful of other countries have already approved Leqembi based on evidence that it slows the progression of Alzheimer’s around 27% — an effect described as modest by some experts.
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- Source: https://www.biopharmadive.com/news/leqembi-european-recommendation-chmp-eisai-biogen-alzheimers/732998/