BOSTON, June 7, 2021 -- The Institute of Clinical and Economic Review (ICER) believes that the FDA, in approving aducanumab (Aduhelm™, Biogen) for the treatment of Alzheimer’s disease, has failed in its responsibility to protect patients and families from unproven treatments with known harms.
Our review of the evidence was concordant with that of many independent experts: current evidence is insufficient to demonstrate that aducanumab benefits patients. The avenue forward has seemed clear: another study would be needed to reduce the substantial uncertainty about the drug’s effectiveness, a requirement of even greater priority because of the drug’s common and potentially serious side effects.
However, instead of waiting for such a trial, the FDA chose to move the goalposts and approve aducanumab based on the surrogate outcome of removing amyloid from the brain rather than the patient-centered outcome of clinical benefit, which has been required of all previous emerging treatments for Alzheimer’s disease. Many other drugs have been shown to remove amyloid from the brain, yet have failed to help patients, making this decision all the more puzzling. Additionally, the FDA granted approval for treatment of all patients with Alzheimer’s disease despite the fact that the drug has been studied only in patients with mild cognitive impairment (MCI) and mild dementia. Trials of other amyloid therapies in later Alzheimer’s disease have all failed. Thus, there appears to be no evidentiary basis to justify the FDA’s decision to extend the label of aducanumab beyond the study populations.
Alzheimer’s disease has a tremendous impact on patients and loved ones, and no one can be insensitive to the hopes and the fears that are part of their daily lives. But no one should assume that approving a drug with such conflicting and uncertain evidence will necessarily help patients and families. On them now falls the decision of whether to use a treatment that may not work, that has modest effects at best, and that causes brain swelling and potential bleeding in approximately 30% of patients. This is the type of situation in which the FDA should play a supremely important role: to protect patients and families by holding firm to a standard that evidence reasonably establish that a therapy benefits patients.
With the approval today, very important questions remain: how will patients be diagnosed; how will insurers cover aducanumab; how will patients be screened for possible side effects; and how can aducanumab be introduced into practice in a way that addresses the systemic disparities across our health care system. Questions about the design of the confirmatory trial now also take center stage.
We will also address the question of fair pricing for a drug that now seems likely to become one of the top selling drugs in the history of the United States. ICER’s preliminary draft report calculated a fair annual price to lie between $2,500-$8,300. Even our most optimistic cost-effectiveness scenario -- which ignores the contradictions within the two pivotal trials and presumes that only the positive trial captures the true benefits of treatment -- aducanumab’s health gains would support an annual price between $11,100-$23,100. The list price of $56,000 per year announced today by the drug maker far exceeds even this optimistic scenario. Our report notes that only a hypothetical drug that halts dementia entirely would merit this pricing level. The evidence on aducanumab suggests that, at best, the drug is not nearly this effective. Nonetheless, even at the lower range of the estimated number of eligible patients, at this price the drug maker would stand to receive well in excess of $50 billion per year even while waiting for evidence to confirm that patients receive actual benefits from treatment.
We look forward to engaging stakeholders, including the manufacturer, in a discussion of how the pricing for aducanumab should reflect its value to patients and families, the substantial uncertainty surrounding its effectiveness, and the scale of its potential use.