— Independent appraisal committee unanimously determined the evidence is not adequate to demonstrate that aducanumab provides a net health benefit—

— In light of substantial uncertainty of patient benefit, policy recommendations call for a lower price to avoid strain on Medicare and Medicaid budgets and to avert financial toxicity for patients; urge experts and policymakers to avoid overstating the potential benefits of treatment; explore options for insurance coverage criteria; and suggest specific rigorous research designs that should be considered as part of any potential Medicare coverage decision with requirements for further evidence development —

BOSTON, August 5, 2021 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report assessing the comparative clinical effectiveness and value of aducanumab (AduhelmTM, Biogen) for the treatment of Alzheimer’s disease. ICER’s report was reviewed at the July 2021 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s three independent evidence appraisal committees.

“The clinical trial history and evidence regarding aducanumab are complex,” said David Rind, MD, ICER’s Chief Medical Officer. “We have spent eight months analyzing the study results, talking with patient groups and clinical experts, and working with the manufacturer to understand their position.  At the conclusion of this effort, despite the tremendous unmet need for new treatments for Alzheimer’s disease, we have judged the current evidence to be insufficient to demonstrate that aducanumab slows cognitive decline, while it is clear that it can harm some patients.

Nonetheless, the FDA has approved this drug, and if Medicare and private insurers choose to provide coverage, millions of patients and families will face the question of whether to use it — which means many patients and families will suffer financial toxicity without knowing whether they are taking a drug more likely to help them than hurt them.  The company had another path open to them.  They could have priced in line with our current best estimate of clinical value at a tenth of their current list price and still expected to make billions of dollars each year. It is unfortunate that they did not choose such a path.”

Voting on Clinical Effectiveness and Contextual Considerations

During the public meeting, the CTAF panelists voted unanimously (15-0) that the evidence was not adequate to demonstrate that aducanumab plus supportive care provides a net health benefit when compared to supportive care alone.

During their deliberations, panel members also weighed the therapies’ other potential benefits, disadvantages, and contextual considerations. The voting highlighted the following aspects as particularly important for payers and other policymakers to note:

  • The acuity of need for people with Alzheimer’s disease;
  • The magnitude of the lifetime impact of the disease;
  • Patients’ ability to achieve major life goals related to education, work, or family life;
  • Caregivers’ quality of life and/or ability to achieve major life goals related to education, work, or family life; and
  • Society’s goal of reducing inequities among patient populations.

Cost-Effectiveness Findings

Consistent with ICER’s process, because the CTAF had already voted unanimously that the evidence did not show a net health benefit for aducanumab, the panel did not take a separate vote on the treatment’s long-term value for money.

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 – which would require an 85-95% discount off the treatment’s US list price of $56,000.  

ICER’s HBPBs are price ranges 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.

Access and Affordability Alert

Approximately 2.5%, or 35,000 out of 1.4 million Alzheimer’s patients eligible for treatment with aducanumab could be treated within five years before crossing the ICER potential budget impact threshold of $819 million per year when taking a health care system perspective.

The purpose of an ICER access and affordability alert is to signal to stakeholders and policy makers that the amount of added health care costs associated with a new service may be difficult for the health system to absorb over the short term without displacing other needed services, creating pressure on payers to sharply restrict access, or causing rapid growth in health care insurance costs that would threaten sustainable access to high-value care for all patients.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, a former US regulator, and representatives from US payers and Biogen — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

  • Biogen should lower the price of aducanumab to a value-based price range determined by independent research to fairly align with demonstrated benefits for patients.  Fair pricing is required to fulfill the social responsibility held by manufacturers to avoid financial toxicity that falls hardest on the most vulnerable patients. 
  • If Medicare chooses to provide coverage following its National Coverage Determination (NCD) process, it should work with input from the National Institutes of Health and other research methodology experts to design a rigorous Coverage with Evidence Development (CED) program requiring patients be enrolled in a randomized controlled trial or a trial using a rigorous quasi experimental “waitlist” research design.
  • Biogen should accelerate the timeline of a confirmatory randomized controlled trial conducted internationally to provide more definitive evidence on the clinical efficacy of aducanumab as well as additional safety data.

ICER’s detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

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.