‘No’ Recommendation for Aduhelm in EU; Biogen to Seek Re-exam
The CHMP, which is part of the European Medicines Agency (EMA), voted against recommending Aduhelm last month, and now has issued its formal ruling. The decision comes despite lobbying efforts by Alzheimer’s Research UK, and the therapy’s accelerated approval in the U.S., under which Aduhelm is being marketed while further studies are done to test its effectiveness.
Aduhelm’s developer, Biogen, is planning to request a re-examination of the CHMP’s opinion. This will involve the submission of documents with detailed grounds for the request, after which the CHMP will have 60 days to re-examine its opinion.
“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, MD, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in a separate press release.
Evans said the CHMP decision “reflects a lack of clear evidence” from the developer that the therapy can improve the lives of patients.
“Biogen must continue collecting essential data to clarify the safety and effectiveness of aducanumab,” Evans said.
Aduhelm is an antibody-based therapy designed to clear from the brain amyloid plaques, which are irregular clumps of protein that are characteristic of Alzheimer’s disease and are thought to drive its symptoms. After early clinical trial data showed that Aduhelm could effectively clear these plaques, Biogen launched two Phase 3 clinical trials, EMERGE (NCT02484547) and ENGAGE (NCT02477800), to test the medication’s effect on cognition and functional decline.
Biogen pulled the plug on those trials in 2019, after an interim analysis indicated that the medication was unlikely to benefit patients. However, the company reversed course once full data from the trials were collected — one showed that Aduhelm treatment significantly slowed cognitive and functional decline in one of the trials, but not the other.
The U.S. Food and Drug Administration (FDA) granted Aduhelm the accelerated approval in June — a move that basically allows Biogen to market the therapy based on the early evidence of amyloid plaque clearance, but still requires the company to conduct further studies testing efficacy on cognition and function.
The FDA’s decision was met with substantial controversy, prompting three members of an advisory committee that had voted strongly against approval to resign in protest, while lawmakers launched an investigation into irregularities during the process. Aduhelm’s high price — about $56,000 per patient per year — also has sparked criticism.
The CHMP, in its ruling, stated that evidence shows Aduhelm can clear amyloid plaques, but that the link between this biological effect and actual improvement in patients’ clinical condition is not clear, so approval was not recommended.
“The last year has seen a complex situation with aducanumab play out differently through EU and US regulatory pathways. What people with Alzheimer’s need is a medicine that improves their lives and the EMA committee’s decision reflects a lack of clear evidence that aducanumab can do that,” Evans said.
Apart from its effectiveness, concerns have been raised concerning Aduhelm’s safety: a recent study found that more than a third of patients given the medication in the Phase 3 trials experienced swelling in the brain, or ARIA-edema. This didn’t cause symptoms in most patients, though in some individuals it can cause enough problems to require hospitalization, and one case of death associated with this side effect is being investigated.
“We understand why the committee couldn’t recommend a licence for aducanumab at this time, but we must also recognise the many thousands of people with Alzheimer’s who continue to be without effective new treatment options,” said Evans.
It’s not yet known whether Biogen will submit a separate application seeking approval of Aduhelm in the U.K. Outside the U.S. and Europe, the medication has been approved in the United Arab Emirates (UAE).
“For Europeans impacted by Alzheimer’s disease, the lack of options to treat its early stages is felt every day,” Singhal said, adding, “The longer we wait, the more people will progress toward more advanced dementia and we may miss the opportunity to potentially treat them.”