The drug hit a block in December when the European Medicine Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended refusal of the application. In response, Biogen formally requested that the committee re-examine its opinion.
On Friday (22 April), however, Biogen announced that it would no longer be pursuing the application: withdrawing the application before the CHMP's re-examination had finished. In a statement, the company says that its interactions with the CHMP had indicated that the available data would not be sufficient to support a positive opinion.
In its letter to the EMA, Biogen notes there will be no consequences of the withdrawal on ongoing clinical trials.
The drug was approved in the US last year: 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.
In Europe, however, the CHMP's December review did not deem this sufficient to grant authorization: saying the link between the reduction of amyloid beta in the brain and clinical improvement had not been established. Furthermore, it noted studies ‘did not show 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’.
Its conclusion was that the benefits of the drug did not outweigh the risks.
Biogen's EMA application was based on two main studies of over 3,000 patients with early-stage Alzheimer’s disease comparing the effects of a low and high dose of Aduhelm with the effects of placebo. The studies looked at how the patients’ symptoms changed after 78 weeks of treatment using a dementia rating scale known as CDR-SB.
“We are thankful to the patients, caregivers and physicians that supported the re-examination process as part of the EMA review,” said Priya Singhal, M.D., M.P.H., Head of Global Safety & Regulatory Sciences and interim Head of Research & Development at Biogen.
“We stand by the safety and efficacy of aducanumab, and we look forward to upcoming data readouts to continue to provide important information on the science of this new class of compound.”
Noting that the last approval of an Alzheimer’s medicine by the EMA dates back to 2002, Alzheimer’s Europe says Biogen's decision will be disappointing news for Europeans affected by the disease.
“Alzheimer Europe will continue to monitor clinical trial developments with great interest and notes the welcome announcement by Biogen about the launch of a phase IV trial of aducanumab in May 2022,"
said the group.
"The organisation hopes that this trial and ongoing trials by other companies will lead to positive results and to the approval by the EMA of the first new treatment against Alzheimer’s disease in over 20 years.
“Alzheimer Europe also calls for continued research into much-needed and anticipated treatment options, including symptomatic treatments for people in more advanced stages of the disease.”
Phase 4 trial set to start in May
Biogen’s decision to abandon the drug in the EU follows a subdued rollout in the US. Earlier this month, a much-anticipated decision from the US Centers for Medicare & Medicaid Services (CMS) confirmed that coverage of the drug will be limited to clinical trials.
Biogen had already halved the price of the drug and started cost-cutting measures across the company including layoffs.
However, last month the company announced new long-term Phase 3 data showing that, after nearly 2.5 years of treatment, Aduhelm continued to reduce two key Alzheimer’s disease pathologies (amyloid beta plaques and p-tau181).
Meanwhile, a Phase 4 trial for the drug – as required by the FDA in its approval last year to help verify the drug’s clinical benefit – is set to start screening patients in May.