Biogen and Eisai's Alzheimer’s Drug Aduhelm Rejected by European Regulators

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Everything was as expected. After the key committee cast a "trend vote" against it in mid-last month, it seemed inevitable that the EU regulatory authority would reject the approval of Aduhelm.

Recently, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has officially issued a negative opinion on the marketing authorization application submitted by Biogen and its partner Eisai for the monoclonal antibody drug Aduhelm intended to treat early Alzheimer's disease (AD).

Last Friday, Biogen said that it would seek a re-examination of the opinion by the CHMP when disclosing this news. Biogen needs to submit a review within 15 days after receiving the opinion. According to EMA rules, CHMP will have 60 days to reassess its opinion. "As part of the re-examination process, we will seek to address the reasons for CHMP's refusal with the aim of making this drug available in the EU," said Dr. Priya Singhal, head of Biogen's R&D, in a statement.

In rejecting Aduhelm, the EMA pointed out some known aspects of the drug. The EMA stated that this antibody medication showed it could reduce β-amyloid plaques in the brain, but the connection between its effect and actual clinical improvement remains questionable. The EMA's decision came after last month’s negative "trend vote" by the CHMP on Aduhelm’s marketing application.

In terms of regulation, the U.S. FDA granted accelerated approval to Aduhelm in June 2021 based on data showing clearance of AD biomarkers. Despite the approval, the FDA also acknowledged that there is currently insufficient evidence to indicate the drug is beneficial to patients.

EMA also pointed out in its negative opinion that the results of two controversial Phase 3 trials (EMERGE and ENGAGE) appear to be contradictory. Biogen explained that an imbalance in rapid progressors and limited exposure to the high dose of Aduhelm could explain the drug's lack of efficacy.

Moreover, the EMA raised questions about the safety of Aduhelm, particularly regarding a serious side effect known as amyloid-related imaging abnormalities (ARIA), which can present as brain bleeding or swelling. Biogen and the FDA are investigating the potential role of Aduhelm in the recent death of a patient reported in the FDA's adverse event tracking system. In this case, a 75-year-old woman in Canada who was receiving Aduhelm treatment died after being diagnosed with ARIA.

EMA stated regarding ARIA: "It is currently unclear whether these abnormalities can be appropriately monitored and managed in clinical practice."

Outside Europe, Biogen and Eisai have also submitted an application for the approval of Aduhelm in Japan, and the progress appears to be optimistic. Japan's Ministry of Health, Labour and Welfare (MHLW) has decided to hold a meeting on December 22 to discuss the drug. In a report to clients last Tuesday, Jefferies analysts suggested that the sudden scheduling of such a meeting (usually held according to a regular schedule) could be a good sign for potential approval. The Jefferies team currently estimates that Aduhelm’s sales in Japan could reach $878 million in the fiscal year ending March 2030, but the drug has only a 50% chance of being approved.

At the same time, Biogen now hopes to launch a post-marketing confirmatory clinical trial in May next year and aims to report data before 2026. If the trial results are negative, the FDA has the option to withdraw the accelerated approval. Due to the lack of convincing data, Biogen is facing significant challenges in selling Aduhelm, with sales reaching only $300,000 in the third quarter of this year, far below expectations. In January 2022, Biogen will face a critical Medicare coverage decision.

Reference Source: Biogen vows to contest EMA rejection of Aduhelm as EU regulators question weak link to Alzheimer's clinical benefit