Aduhelm Most Appropriate for Early-stage Alzheimer’s, Experts Say

Aduhelm (aducanumab), approved for Alzheimer’s disease in the U.S., is most appropriate for people with mild cognitive impairment (MCI) due to the disease or early Alzheimer’s dementia, the disorders for which it was tested in clinical trials and subsequently approved, according to experts from the scientific community.

The experts discussed the path forward for Aduhelm following its U.S. approval at a meeting convened by the Alzheimer’s Association, which published a press release with details from the meeting.

The association reaffirmed its stance that the medication’s price — $56,000 per year, according to Biogen (which developed the therapy alongside Eisai) — is “simply unacceptable.”

“The price announced by the manufacturer will pose an insurmountable barrier to access, complicate and jeopardize sustainable access to this treatment, and may further deepen issues of health equity,” Maria Carrillo, PhD, the association’s chief science officer, said in her welcome remarks at the meeting.

The association said it is committed to working with private insurers and the Centers for Medicare and Medicaid Services to ensure access to the therapy for appropriate patients.

Experts noted that clinical trials of Aduhelm specifically enrolled participants with MCI due to Alzheimer’s disease and early Alzheimer’s dementia. As such, the treatment “is not appropriate for people in all stages of Alzheimer’s,” they said. (The FDA approval indicates Aduhelm is “for the treatment of Alzheimer’s disease,” with no additional restrictions.)

“We must continue to diversify the treatment pipeline to address this devastating disease at all stages through multiple pathways and for all communities, as we have with other major diseases,” the association states.

Data from early clinical trials showed that the medication could lower levels of beta-amyloid plaques in the brains of people with early Alzheimer’s — these abnormal protein plaques are a hallmark of Alzheimer’s and are thought to drive disease progression.

However, Biogen halted development of Aduhelm in 2019, after an interim analysis of the Phase 3 clinical trials ENGAGE (NCT02477800) and EMERGE (NCT02484547) suggested the medication was unlikely to benefit participants. The trials enrolled about 3,300 people with MCI due to Alzheimer’s disease or early Alzheimer’s dementia.

After this decision was made, more data were collected and showed that, contrary to the interim analysis, one of the trials (EMERGE) had met its primary endpoint: treatment with Aduhelm slowed the decline in a measure of functional and cognitive abilities, relative to a placebo. Based on the findings, Biogen reversed course, announcing plans to seek FDA approval.

The Alzheimer’s Association had campaigned for FDA approval, saying it would be inhumane to deny people a medication that might slow the progression of an otherwise untreatable disease. Other experts, however, including the majority of those on an FDA advisory committee, said that there wasn’t enough data to ensure the medication’s effectiveness and justify its approval.

Earlier this month, the FDA approved Aduhelm under the accelerated approval pathway. This pathway allows for earlier approval based on a surrogate endpoint as a marker, such as a laboratory measure — in this case, the reduction in beta-amyloid observed in early clinical trials — while still requiring the therapy’s makers to conduct additional studies of its efficacy.

The approval “begins a new era in Alzheimer’s treatment and research,” the association states. “History has shown us that approvals of the first drug in a new category will invigorate the field, increase investments in new treatments and generate greater innovation.”