- On Monday the U.S. Food and Drug Administration (FDA) made its highly-anticipated call on Biogen’s Alzheimer’s candidate, Aduhelm (aducanumab)
- The regulatory agency approved the drug under its Accelerated Approval pathway, which allows patients to gain access to the drug even if there remains some uncertainty about its clinical benefit
- Alzheimer’s is an incredibly complex neurological disorder and one of the most prominent challenges facing healthcare today, with lots of treatments missing the mark in the past. Because of its history, dotted with early-stage failures and no new drug approvals since 2003, the FDA’s decision is historical and will serve as a point of reference for future drug approvals in similar areas. Read our INSIGHT here:
MARYLAND, United States – On Monday, the U.S. Food and Drug Administration (FDA) made its highly-anticipated call on Biogen’s Alzheimer’s candidate, Aduhelm (aducanumab).
The regulatory agency approved the drug under its Accelerated Approval pathway, which allows patients to gain access to the drug even if there remains some uncertainty about its clinical benefit.
Alzheimer’s is an incredibly complex neurological disorder and one of the most prominent challenges facing healthcare today, with lots of treatments missing the mark in the past. Because of its history, dotted with early-stage failures and no new drug approvals since 2003, the FDA’s decision is historical and will serve as a point of reference for future drug approvals in similar areas.
Aduhelm’s FDA Journey
The road to approval has been peppered with uncertainty from within pharma, and media speculation added an altogether new kind of pressure to the FDA’s committee.
In March 2019, Biogen and its Aduhelm partner Eisai discontinued a number of relevant trials after an independent data monitoring committee indicated they were unlikely to hit their primary endpoint.
However, the blow was short lived and later in the year the two drugmakers announced plans to seek FDA approval based on the Phase 3 EMERGE trial.
The study in question ultimately did meet its primary endpoint, demonstrating a notable reduction in clinical decline from Alzheimer’s. The company also announced that the data from a subset of participants in the Phase 3 ENGAGE Study who were given suitable exposure to high dose aducanumab backed the findings from EMERGE.
In November 2020, an FDA advisory panel voted heavily against approval of the anti-amyloid antibody for use in the indication, citing conflicting results from various trials outside the ENGAGE study. At the time, the panel gave one yes, eight no and two uncertain votes on the matter, ultimately deciding that the ENGAGE study did not provide strong evidence that supported the effectiveness of Aduhelm for the treatment of Alzheimer’s disease.
In a statement released on Monday, the FDA acknowledged the unusually public nature of the regulatory decision, noting that it is “well-aware of the attention surrounding this approval,” following years of debate surrounding the weigh up between the drug’s efficacy and safety, compared to the huge area of unmet need that Alzheimer’s presents.
“We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders. With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review.
“Further, the data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit. There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.”
Do Patient Barriers Remain?
Drug approval does not equal drug access, and the drug’s price remains yet to be seen.
On May 7, the Institute for Clinical and Economic Review (ICER) published a Draft Evidence Report on the comparative clinical effectiveness and value of Aduhelm for Alzheimer’s Disease, rating the drug’s evidence as being “insufficient” to demonstrate a net health benefit for patients.
Using the combined results from two contradictory Phase 3 randomized trials for a base-case cost-effectiveness analysis, ICER concluded there was a small overall health gain commensurate with value-based prices at traditional cost-effectiveness thresholds between $2,500-$8,300 per year.
If evidence suggests no health benefit for aducanumab, then aducanumab’s value-based price would be $0, whereas an optimistic scenario considering only the favorable pivotal trial supports an annual price for aducanumab between $11,100-$23,100.
On the release of the report, David Rind, MD, ICER’s Chief Medical Officer, said, “[Alzheimer’s] is a condition that people dread like no other, and the first therapy that effectively cures or stops the progression of the disease will warrant a very high price in the US health system. However, the clinical trial history and evidence regarding aducanumab are complex, and we believe that at the current time the evidence remains insufficient to determine whether the drug provides an overall health benefit.
“This is an area of tremendous unmet need, but this treatment has important side effects, and its wide use would have important ramifications for patients and health care budgets, making it all the more important that we know whether a therapy like aducanumab is, or is not, effective.”
This particular drug approval has spurred a sizeable portion of the medical industry and the general public to call the FDA’s credibility into question, with Public Citizen’s Health Research Group claiming the regulatory body “inappropriately collaborated” with Biogen to “rush the lucrative, unproven treatment.”
Dr. Michael Carome, director of the Research Group, believes that the decision shows a “stunning disregard for science and eviscerates the agency’s standards for approving new drugs.
“Because of this reckless action, the agency’s credibility has been irreparably damaged.”
He added, “Approving aducanumab despite the lack of evidence of effectiveness plus the well-documented risk of serious harm will raise false hope for millions of Alzheimer’s patients and their families, potentially bankrupt the Medicare program because of the drug’s projected exorbitant price and impede for years the development of other experimental treatments for the disease.”
A number of healthcare professionals are also skeptical about actually giving the therapy to their patients, such as Aroonsiri Howell, M.D, M.P.H., Assistant Professor of Medicine, who took to Twitter to express: “Not only will I NOT prescribe #Aducanumab, I’ll share the unconvincing results w/ all colleagues so no one prescribes it.”
Aduhelm Sets the Bar for Future Alzheimer’s R&D
What sets Biogen’s efforts apart from the noise is its mechanism of action. Up until this point, multiple Alzheimer’s candidates designed to eliminate or prevent amyloid accumulation failed to demonstrate an improvement in cognition and memory in later-phase clinical trials, even in instances when there was biomarker and magnetic resonance imaging (MRI) evidence that the amyloid was cleared.
At the very core of the decision, Aduhelm is now the first approved treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain.
This could be seen as a verdict on the broader amyloid hypothesis and ultimately have a knock-on effect for Alzheimer’s research and development (R&D) going forward.
“This FDA drug approval ushers in a new era in Alzheimer’s treatment and research,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer. “History has shown us that approvals of the first drug in a new category invigorates the field, increases investments in new treatments and encourages greater innovation. We are hopeful and this is the beginning — both for this drug and for better treatments for Alzheimer’s.”
By granting the approval via the Accelerated Access pathway, the agency upended years of regulatory precedent, creating new potential and more hope for treatments with considerable potential but perhaps not perfect trial data.