— Accepting the uncertainty associated with the positive estimate obtained from pooled data from both pivotal trials, the revised report finds the price range needed to reach standard cost-effectiveness thresholds is $3,000-$8,400, representing an 85%-95% discount from the announced list price —

— At July 15 public meeting, a roundtable of key stakeholders — including Biogen, the Alzheimer’s Association, and a former FDA and CMS chief — will discuss the mismatch between the announced price and value-based estimates, coverage options for Medicare and private payers, potential research designs for the required confirmatory trial of aducanumab, and the impact of the approval of aducanumab on future development of treatments for Alzheimer’s disease —

BOSTON, June 30, 2021 – The Institute for Clinical and Economic Review (ICER) today released its revised Evidence Report assessing the comparative clinical effectiveness and value of aducanumab (Aduhelm™, Biogen) for the treatment of Alzheimer’s disease. A draft version of this report was previously open for a four-week public comment period; this updated version reflects changes made based on the breadth of the FDA label, the treatment’s announced price, and comments received from the manufacturer, patient groups, clinicians, and other stakeholders. Detailed responses to public comments can be found here.

“Individuals and families dread Alzheimer’s disease, and the first therapy that effectively halts or reverses dementia will warrant a very high price in the US health system,” said David Rind, MD, ICER’s Chief Medical Officer. “However, the clinical trial history and evidence regarding aducanumab are complex, and we agree with many independent experts that the current evidence is insufficient to know whether or not aducanumab slows the loss of cognition. Many other drugs have been shown to remove amyloid from the brain yet failed to improve the lives of those with Alzheimer’s disease; none of these other treatments received FDA approval. After months of delving into the data, and working with patient groups, clinical experts, and the manufacturer to gain their perspectives, our judgment remains that the evidence on aducanumab is insufficient to be able to demonstrate that patients get benefits that would outweigh the risks and harms of this treatment.”

Public Meeting

This Evidence Report will be reviewed at a virtual public meeting of the California Technology Assessment Forum (CTAF) on July 15, 2021. CTAF is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy. These experts will hear a presentation of the clinical evidence and economic models, as well as testimony from patients, neurologists and Biogen, before voting on aducanumab’s 1) net health benefit, 2) other potential benefits and important contextual considerations, and 3) long-term cost-effectiveness. 

Following these votes, ICER will facilitate a policy roundtable discussion among several key stakeholders:

  • Biogen
  • The Alzheimer’s Association
  • Mark McClellan, MD, PhD, former FDA Commissioner and former CMS Administrator
  • Patients and caregivers living with the disease
  • Expert neurologists
  • US commercial payers

This cross-section of stakeholders will engage with the looming policy questions related to aducanumab’s approval, such as: how the confirmatory trial should be designed; how patients should be diagnosed and screened for side effects; how Medicare and private insurers should cover aducanumab; how much this single treatment will swell the Medicare budget, and how much of the financial burden will fall directly on individual patients and families; how this approval may change evidence requirements and clinical studies for future Alzheimer’s treatments; if there are opportunities to strengthen the FDA’s accelerated approval pathway; and if policymakers may now seek reforms to better align a drug’s price with its demonstrated ability to improve patients’ lives.

Key Clinical Findings

While the evidence suggests that aducanumab’s side effects are both common and potentially serious, the two Phase III clinical trials produced contradictory results as to whether aducanumab slows the progression of the disease or improves cognition. ICER has determined the evidence is “insufficient” (I) to show a net health benefit for patients with mild cognitive impairment due to Alzheimer’s disease, as well as for patients with mild Alzheimer’s disease.

If we had rated the net benefit for the entire population of individuals with Alzheimer’s disease specified in the FDA label, our evidence rating would likely have been lower: for the population of patients with severe Alzheimer’s disease, it is reasonably likely that aducanumab’s harms outweigh any potential benefits.

Key Cost-Effectiveness Findings

Despite substantial uncertainty regarding aducanumab’s health benefits, ICER’s base-case cost-effectiveness analysis combined the results from the two contradictory phase III randomized trials. ICER’s health-benefit price benchmark (HBPB) range for aducanumab is $3,000-$8,400 per year for patients with early Alzheimer’s disease. This range is slightly higher than what was included in our preliminary draft report, and the change is largely due to the FDA requiring fewer MRIs than what patients received during the clinical trials.

If patients with advanced dementia are also treated with aducanumab, consistent with the FDA’s broader label, ICER’s HBPB range for the therapy would be lower. As it is, ICER’s HBPB range for aducanumab would require an 85%-95% discount off the treatment’s announced annual US list price of $56,000 per year.

ICER also calculated what a fair price would be for a hypothetical chronic maintenance therapy that halted the progression of dementia in people with Alzheimer’s disease. While this hypothetical treatment could be priced between $50,000-$70,000 per year and still meet commonly cited thresholds for long-term cost-effectiveness, aducanumab is not close to being this effective.

ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.