ICER Updates Report on Aducanumab Pricing, Affirms Agent Is Not Cost-Effective

David Rind, MD

A newly published revised report from the Institute for Clinical and Economic Review (ICER) suggests that Biogen must drastically reduce the price of its newly approved anti-amyloid agent for the treatment of Alzheimer disease (AD), aducanumab (Aduhelm), in order for the therapy to be considered cost-effective for patients. The current list price of aducanumab has been set at $56,000 annually.¹

This new report affirms the prior published report from ICER, which suggested that in order for the agent to be cost-effective, its price would be between $2500 and $8300 per patient per year. When calculating the price based on assumed "optimistic" treatment benefits—relying only on the results of the positive study—and would price the agent between $11,100 and $23,100 for it to be considered cost-effective. Based on an assumption of "conservative" treatment benefits, the cost-effective range was reduced to between $1200 and $4200.²

Most notably, the new report draws its conclusion based on the established level of efficacy—which has been a subject of much debate among the AD community—and calculated that the treatment would be cost-effective only if listed at prices ranging from $3000 to $8400, a massive reduction equaling 85% to 95% of the current price, respectively.¹ Many analysts have reported that the current price is expected to greatly stretch the Medicare budget for drugs administered by doctors, in part due to the average age and coverage of the AD patient population.

“Individuals and families dread Alzheimer disease, and the first therapy that effectively halts or reverses dementia will warrant a very high price in the US health system,” David Rind, MD, chief medical officer, ICER, said in a statement.³ “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 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,” Rind continued.

READ MORE: International Perception of Aducanumab: Will Other Regulatory Agencies Approve the Agent?

ICER also announced that its new evidence report is expected to be reviewed at a virtual public meeting of the California Technology Assessment Forum (CTAF) on July 15, 2021. The CTAF meeting is among the 3 independent evidence appraisal committees that ICER conducts, which includes medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy. At the meeting, those individuals will see a presentation of the clinical evidence and economic models, as well as testimony from patients, neurologists and Biogen, before voting on the following: aducanumab’s net health benefit; aducanumab’s other potential benefits and important contextual considerations; and aducanumab’s long-term cost-effectiveness. Following that vote at CTAF, ICER noted that it will facilitate a policy roundtable discussion among several key stakeholders, including Biogen; the Alzheimer’s Association; Mark McClellan, MD, PhD, a former FDA Commissioner and former CMS Administrator; patients and caregivers living with the disease; expert neurologists; and US commercial payers.

The FDA decision to approve aducanumab followed ongoing debate within the medical community. It all began in March 2019, when Biogen announced that it was discontinuing the 2 phase 3 clinical trials evaluating the anti-amyloid agent—EMERGE (NCT02484547) and ENGAGE (NCT02477800), as well as a phase 2 safety study, EVOLVE (NCT03639987)—which was followed by an October 2019 announcement that the company had reversed course on its decision. Later that year at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) annual meeting, December 4-7, 2019, in San Diego, California, new data from EMERGE and a post hoc analysis of a subset of patients who received high-dose treatment in ENGAGE were presented, suggesting that there were statistically significant changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores, with P values of .010 or .031 based on cutoff dates. At that point, Biogen declared its intention to submit the agent to the FDA for review.⁴

ICER noted that Biogen “explored possible explanations for the discordant results between the two trials; they concluded that the timing of post-Protocol Version 4 allowed more patients in EMERGE than ENGAGE to receive the full high-dose regimen (28.8% vs. 22.3%) and that randomization had failed to balance ‘rapid progressors’ in ENGAGE.”³

The original biologics license application (BLA) for aducanumab was submitted to the FDA in July 2020, at which time it was accepted for review. As such, the data were reviewed by the agency’s Peripheral and Central Nervous System Drugs Advisory Committee in November 2020, who ultimately voted to not recommend regulatory approval. Then, in January 2021, the agency extended the review period by 3 months to June 7, 2021, after Biogen submitted additional clinical data and analyses in response to an information request from the FDA.

The NeurologyLive Mind Moments podcast recently featured a number of experts in AD to inquire about their reactions to aducanumab’s approval in Episode 39, "A Controversial FDA Decision." It features insights from a number of individuals in the Alzheimer disease space, including neurologists, psychiatrists, and advocacy partners who share their varying and nuanced opinions on this decision to better understand not only what this approval means for clinical care, but what the downstream effects of it may be. Listen to their varying insights below.

REFERENCES
1. Lin GA, Whittington MD, Synnott PG, McKenna A, Campbell J, Pearson SD, Rind DM. Aducanumab for Alzheimer’s Disease: Effectiveness and Value; Evidence Report. Institute for Clinical and Economic Review, June 30, 2021. Accessed July 1, 2021. https://icer.org/assessment/alzheimersdisease-2021/.
2. Lin GA, Whittington MD, Synnott PG, McKenna A, Campbell J, Pearson SD, Rind DM. Aducanumab for Alzheimer’s Disease: Effectiveness and Value; Draft Evidence Report. Institute for Clinical and Economic Review, May 5, 2021. Accessed July 1, 2021. https://icer.org/assessment/alzheimersdisease-2021/.
3. In Revised Evidence Report, ICER Confirms Judgment That Evidence is Insufficient to Demonstrate Net Health Benefit of Aducanumab for Patients with Alzheimer’s Disease. News release. ICER. Published June 30, 2021. Accessed July 1, 2021. https://icer.org/news-insights/press-releases/in-revised-evidence-report-icer-confirms-judgment-that-evidence-is-insufficient-to-demonstrate-net-health-benefit-of-aducanumab-for-patients-with-alzheimers-disease/
4. Biogen plans regulatory filing for aducanumab in Alzheimer’s Disease based on new analysis of larger dataset from phase 3 studies. News release. Biogen and Eisai. October 22, 2019. Accessed July 1, 2021. https://www.biospace.com/article/releases/biogen-plans-regulatory-filing-for-aducanumab-in-alzheimer-s-disease-based-on-new-analysis-of-larger-dataset-from-phase-3-studies