CMS Policy Trumps FDA Approval for Aducanumab
Surprising turn of events is a strong message to the pharmaceutical industry about the acceptable developmental pathway for this drug class.
Last year in this column, I expressed disappointment in the decision by the FDA to grant regulatory approval for the marketing of aducanumab (Aduhelm) for the treatment of patients with Alzheimer disease (AD) based on a surrogate end point that had not been clearly linked to clinical improvement or slowing of the disease.1
At that time, most of the large commercial payers had decided to not cover the cost of treatment. The Centers for Medicare & Medicaid Services (CMS) stated that a national coverage determination (NCD) hearing was to be convened and it would take approximately 9 months for that process to be completed. Patient advocacy groups, most notably the Alzheimer’s Association, lauded the drug as a historic breakthrough therapy and were advocating for broad access to treatment.2 Several large health care systems said that they would not offer the treatment pending more data, a decision that was not overly brave, considering that there was essentially no way to get paid for providing this expensive therapy.
Having become a bit of a cynic in my later years, I feared that the necessary influences would be applied in the proper places, resulting in a shift ofpolitical and public opinion toward funding this treatment, despite controversial and sparse evidence of efficacy and definitive evidence of harm. So, what has developed in the past year regarding antiamyloid monoclonal antibody treatments?
In the face of minimal sales and a huge financial fallout, Biogen/Eisai said in January 2022 that they would reduce the cost of aducanumab by 50% to an average of approximately $28,000 per year. This move did not lead to any appreciable increase in utilization, as major payers did not reconsider coverage and the CMS had not yet completed the NCD process. In April 2022, the CMS finalized Medicare coverage policy for monoclonal antibodies targeting amyloid for the treatment of AD. The coverage determination had 2 major elements:
Medicare will cover monoclonal antibodies targeting amyloid or plaque for the treatment of AD that receive traditional approval from the FDA under coverage with evidence development.
For drugs that the FDA has not determined to have shown a clinical benefit or that receive an accelerated FDA approval, Medicare will cover in the case of FDA or National Institutes of Health approved trials. Under this NCD, the CMS will support the FDA by covering the drug and any related services, including, in some cases, PET scans if required by trial protocol for individuals with Medicare who are participating in these trials.3
This NCD is noteworthy for 2 reasons. First, it did not address just aducanumab but rather the entire drug class, which is important, given the number of agents in various stages of clinical development. Second, it signaled that the CMS was not going to broadly cover the treatment unless there was adequate evidence of efficacy and safety to warrant traditional FDA approval. This was a strong message to the pharmaceutical industry concerning the acceptable development pathway for these drugs.
In May 2022, Biogen said that its CEO would step down, along with most of the commercial Aduhelm marketing team. This essentially marked the end of the commercial development of aducanumab. Biogen failed to successfully introduce this therapy into broad clinical use, with less than $6 million in sales since Aduhelm’s approval.4,5 The partnership between Biogen and Eisai is shifting its attention to gaining approval for lecanemab, another antiamyloid monoclonal antibody, with suggestions that Eisai will lead the regulatory effort this time. The Clarity AD confirmatory trial (NCT03887455) of lecanemab is expected to have early data reported in fall 2022. Anticipating the final CMS policy decision, Eli Lilly announced delays in the development plan for its candidate, donanemab, so that larger clinical trials with efficacy and safety end points could be completed later in 2022. The company abandoned its plans to pursue accelerated approval based on surrogate end points.6
On June 15, 2022, Genentech announced that crenezumab was ineffective at preventing the development of cognitive decline in patients with autosomal dominant AD.7 This was a study of patients with a genetic predisposition to develop early AD who were enrolled prior to the onset of cognitive decline.
There were high hopes for this trial given the early introduction of treatment, which was hypothesized to be most effective prior to the onset of clinical signs and symptoms. Although the results from this unique subset of patients may not predict efficacy in typical AD, it is one more study that questions the validity of the amyloid theory as a treatment target for AD.
We all remain hopeful for a meaningful breakthrough in the treatment of AD, a disease that affects more than 6 million individuals in the United States, with devastating consequences for patients and families, but this saga reminds us that there are no shortcuts and that rushing treatments to market for business purposes is not ethical or helpful. The actions taken by CMS in this case should provide some reassurance that one governmental agency is willing to take an evidence-based position on policy, whereas another is not. Perhaps the system of checks and balances is still working. Health system pharmacists must remain cognizant of the evidence behind new drug approvals, contribute to decisions that are in the best interest of patients, and support responsible use of limited health care resources available in the community.
About the Author
Curtis E. Haas, PharmD, FCCP, is director of pharmacy for the University of Rochester Medical Center in New York.
1. Haas CE. Aducanumab may indicate erosion of drug approval standards. Pharmacy Times Health-System Edition™. September 1, 2021. Accessed July 6, 2022. https://www.pharmacytimes.com/view/aducanumab-may-indicate-erosion-of-drug-approval-standards
2. Alzheimer’s Association welcomes FDA approval of Aducanumab. Alzheimer’s Association. June 7, 2021. Accessed July 6, 2022. https://www.alz.org/news/2021/alzheimers-association-fda-approval-aducanumab
3. CMS finalizes Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. Center for Medicare & Medicaid Services. April 7, 2022. Accessed July 6, 2022. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment
4. Robbins R. Biogen C.E.O. will step down after disastrous launch of Alzheimer’s drug. The New York Times. May 3, 2022. Accessed July 6, 2022. https://www.nytimes.com/2022/05/03/business/biogen-aduhelm-michel-vounatsos.html
5. Liu A. Biogen sends CEO to the exit, abandons Aduhelm sales team in $1B overhaul. Fierce Pharma. May 3, 2022. Accessed July 6, 2022. https://www.fiercepharma.com/pharma/biogen-ceo-steps-down-amid-aduhelm-fallout-biotech-trims-commercialteam-1b-cost-cutting
6. Gardner J. Lilly slows FDA submission of Alzheimer’s drug after Medicare decision. Biopharma Dive. February 3, 2022. Accessed July 6, 2022. https://www.biopharmadive.com/news/eli-lilly-fda-donanemab-slow-submission-alzheimers/618258/
7. Genentech provides update on Alzheimer’s prevention initiative study evaluating crenezumab in autosomal dominant Alzheimer’s disease. Genentech. News release. June 15, 2022. Accessed July 6, 2022. https://www.gene.com/media/press-releases/14957/2022-06-15/genentech-provides-update-on-alzheimersabout