EMA Committee Votes Against Approving Aduhelm in Europe
The EMA’s Committee for Medicinal Products for Human Use, known as CHMP, is expected to issue a formal ruling based on this so-called negative trend vote after its meeting in mid-December. But the regulatory agency usually follows the CHMP’s recommendations in approving, or not, an investigational therapy.
Biogen said it will continue to work with the EMA and CHMP toward making Aduhelm available to patients in Europe.
“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab [Aduhelm] has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease,” Priya Singhal, MD, head of global safety and regulatory sciences, and interim head of research and development at Biogen, said in a press release.
Aduhelm is an antibody therapy designed to remove from the brain amyloid plaques, or irregular clumps of protein that are characteristic of Alzheimer’s and lead to its symptoms. The therapy is given by infusion into the bloodstream (intravenously).
A decision by the U.S. Food and Drug Administration (FDA) in June to grant Aduhelm accelerated approval had prompted substantial controversy. Three members of an FDA advisory committee, which voted overwhelmingly against approval, resigned in protest.
At issue is Aduhelm’s effectiveness.
After early clinical trial data indicated that the therapy could effectively clear amyloid plaques, Biogen launched two Phase 3 clinical trials — EMERGE (NCT02484547) and ENGAGE (NCT02477800) — to test whether Aduhelm might slow the decline in cognition that is the hallmark of the disease.
When an interim analysis suggested that the therapy was unlikely to benefit patients, Biogen terminated those trials in 2019.
However, once all available data from the stopped trials were collected and analyzed, it was discovered that one trial — but not the other — had actually met its goal, with Aduhelm treatment significantly slowing the decline in cognitive function relative to a placebo.
Biogen then applied for approval of Aduhelm in the U.S. The therapy was granted accelerated approval — essentially meaning that it would be made available to patients based on the early clinical data that showed it cleared amyloid plaques, but also requiring Biogen to conduct more tests for efficacy.
In a reversal of the June decision a month later, the FDA in July limited Aduhelm’s use to patients with mild Alzheimer’s, updating the treatment’s label.
A recent data analysis of the EMERGE and ENGAGE clinical trials has shown that treatment with Aduhelm significantly correlated with lower blood levels of p-tau181, a disease biomarker, and lesser cognitive and functional decline in Alzheimer’s patients.