Biogen vows to contest EMA rejection of Aduhelm

 Biogen knew what was coming: After a key committee's negative “trend vote,” a rejection of Aduhelm from EU authorities seemed inevitable. So when the rebuff did come, the biotech pounced.

Drug reviewers at the European Medicines Agency (EMA) have officially adopted a negative opinion (PDF) on Biogen and partner Eisai’s application for Aduhelm to treat early-stage Alzheimer’s disease. In revealing the snub Friday, Biogen said it will seek a reexamination of the opinion by the Committee for Medicinal Products for Human Use (CHMP).

The biotech needs to file for reexamination within 15 days of receiving the opinion, and the committee has 60 days to reevaluate its opinion, per EMA rules.

“As part of the re-examination process, we will seek to address the CHMP’s grounds for refusal, with the goal of making this medicine available in the EU,” Priya Singhal, M.D., Biogen’s interim R&D head, said in a statement.

In refusing Aduhelm, the EMA pointed to some known caveats in the drug’s profile. The antibody drug showed it can reduce amyloid beta plaques in the brain, but the effect’s link with actual clinical improvement remains in question, the EMA said. The EMA decision comes after a negative “trend vote” on the Aduhelm application from the CHMP last month.

Across the pond, the U.S. FDA cleared Aduhelm in June under the accelerated approval pathway based on its protein clearance biomarker data. Despite the approval, the U.S. agency acknowledged that there wasn’t enough evidence to show that the drug benefits patients.

In its rejection, the EMA also flagged seemingly conflicting results from the two controversial phase 3 trials called EMERGE and ENGAGE. For its part, Biogen says an imbalance in disease fast progressors and limited exposure to a higher dose of Aduhelm explain the drug’s lack of showing.

Further, the EMA took issue with Aduhelm’s safety profile, especially a dangerous side effect called amyloid-related imaging abnormalities (ARIA), which may show up as brain bleeding or swelling. Biogen and the FDA are probing Aduhelm’s potential role in a patient’s death that was recently reported to the FDA’s adverse events tracking system. In the case, a 75-year-old woman in Canada who had taken Aduhelm died after being diagnosed with ARIA.

“[I]t is not clear that the abnormalities can be properly monitored and managed in clinical practice,” the EMA said of ARIA.

Besides Europe, Biogen and its partner Eisai have an outstanding application for Aduhelm in Japan. The country’s Ministry of Health, Labour and Welfare will hold a meeting (Japanese) to discuss the drug Dec. 22. In a Tuesday note to clients, analysts at Jefferies figured the sudden gathering of such a meeting—which usually takes place on a regular schedule—could be a good sign for a potential approval. The Jefferies team currently estimates Aduhelm could reach $878 million sales in Japan in the fiscal year ending in March 2030, but only assigned a 50% chance of approval there.

Meanwhile, Biogen now looks to launch an FDA-mandated confirmatory trial next May and report data by 2026. If the trial turns out negative, the FDA has the option to yank its accelerated approval. Without convincing data, Biogen is having a hard time selling Aduhelm, and a key Medicare coverage decision looms in 2022.

https://www.fiercepharma.com/pharma/biogen-vows-to-contest-ema-rejection-aduhelm-eu-regulators-weak-link-to-alzheimer-s-clinical