On Thursday, the EMA’s human medicines committee (CHMP) recommended refusal of the marketing authorization for Aduhelm, Biogen’s medicine for the Alzheimer’s disease, which was controversially approved in the US earlier this year.
Approval in the US was granted based on data from clinical trials showing the effect of Aduhelm on reducing amyloid beta plaques in the brain: with the accumulation of such plaques a feature of Alzheimer’s disease.
The CHMP, however, did not deem this sufficient to grant authorization.
“The EMA noted that although Aduhelm reduces amyloid beta in the brain, the link between this effect and clinical improvement had not been established,” said the agency. “Results from the main studies were conflicting and did not show overall that Aduhelm was effective at treating adults with early stage Alzheimer’s disease.
“In addition, the studies did not show that the medicine was sufficiently safe as images from brain scans of some patients showed abnormalities suggestive of swelling or bleeding, which could potentially cause harm. Furthermore, it is not clear that the abnormalities can be properly monitored and managed in clinical practice.
“Therefore, the agency’s opinion was that the benefits of Aduhelm did not outweigh its risks.”
The CHMP assessed efficacy, safety and biomarker data from a global clinical development program of around 3,600 patients.
'European patients deserve access to innovative treatments'
Responding to the EMA’s announcement, Biogen said on Friday it would seek a re-examination of the CHMP’s opinion. In order to do so, it must set out its grounds for requesting the re-examination.
Once the EMA has received an official request, it will have 60 days to re-examine its opinion.
“For Europeans impacted by Alzheimer’s disease, the lack of options to treat its early stages is felt every day. The longer we wait, the more people will progress toward more advanced dementia and we may miss the opportunity to potentially treat them,” said Priya Singhal, M.D., M.P.H., Head of Global Safety & Regulatory Sciences and interim Head of Research & Development at Biogen.
“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. European patients deserve access to innovative treatments for Alzheimer’s disease.”
In June, the US Food and Drug Administration (FDA) granted accelerated approval for ADUHELM (aducanumab-avwa) 100 mg/mL injection for intravenous use as the first Alzheimer’s disease treatment to address a defining pathology of the disease by reducing amyloid beta plaques in the brain. Aduhelm is also approved in the United Arab Emirates.
Aduhelm is a monoclonal antibody directed against amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. The accelerated approval of Aduhelm in the US was granted based on data from clinical trials showing the effect of Aduhelm on reducing amyloid beta plaques, a surrogate biomarker that is ‘reasonably likely’ to predict clinical benefit, in this case a reduction in clinical decline, according to Biogen.
