Biogen has directed a response to the US Centers for Medicaid and Medicare Services’ (CMS) over the CMS’ draft decision last month (January 2022) to restrict Medicare coverage for anti-beta-amyloid drugs for treating Alzheimer’s disease, such as Biogen’s/Eisai’s Aduhelm (aducanumab), only to patients taking part in approved clinical trials. The CMS decision, if finalized, would be considered a setback for drugs in this class, including for Biogen’s/Eisai’s drug, which is projected by analysts as a potential blockbuster. The CMS decision is also drawing criticism from certain members of Congress and patient-advocacy groups.

Aduhelm was approved under the accelerated approval pathway by the US Food and Drug Administration (FDA) in June 2021. The accelerated approval pathway provides patients with a serious disease earlier access to drugs when there is an expectation of clinical benefit despite some uncertainty about the clinical benefit. Accelerated approval is based upon the drug’s effect on a surrogate endpoint—an endpoint that reflects the effect of the drug on an important aspect of the disease—where the drug’s effect on the surrogate endpoint is expected, but not established, to predict clinical benefit. The accelerated approval pathway requires the company to verify clinical benefit in a post-approval trial. If the sponsor cannot verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.

The FDA’s approval of Aduhelm was the first approval in almost two decades of a new treatment for Alzheimer’s disease but its approval came with some issues. Prior to getting the accelerated approval by the FDA, an FDA advisory committee had earlier recommended not to approve the drug, citing the need for additional research. Recommendations by FDA advisory committees are non-binding, but are usually in line with final FDA decisions, although not in this particular case.

The CMS’ draft decision
Last month (January 2022), the CMS issued a draft decision to restrict coverage for Biogen’s/Eisai’s Aduhelm (aducanumab) only to patients taking part in approved clinical trials. It was part of a proposed national coverage determination (NCD) decision memorandum by the CMS that would set a new precedent for restricting coverage of all FDA-approved drugs using monoclonal antibodies that target amyloid for the treatment of Alzheimer’s disease through coverage with evidence development (CED), meaning that FDA-approved drugs in this class would be covered for people with Medicare only if they are enrolled in qualifying clinical trials. Medicare is the US healthcare program for individuals 65 or older.

The CMS opened its January 11, 2022, proposal to public comments for 30 days and will make a final determination on Medicare coverage by April 11, 2022.  If the proposed NCD is finalized, CMS says it will review each submitted clinical trial to determine whether it meets the criteria specified in the proposed NCD. In addition to CMS-approved trials, National Institutes of Health (NIH) sponsored clinical trials would be covered under this proposed NCD as well. Medicare patients participating in these trials would be eligible to receive coverage of the drug, related services, and other routine costs. Currently, Aduhelm is the only mAb directed against amyloid beta approved by the FDA for the treatment of Alzheimer’s disease although there are other such drugs by other companies in development.

Biogen, others offer feedback
In its open letter to the CMS, Biogen disagreed with the CMS’s proposal and offered a three-pronged approach to real-world evidence generation that would complement rather than duplicate existing randomized controlled trials and answer CMS’ questions on the drug. The proposed approach includes:

• A focused registry, such as the International Collaboration for RealWorld Evidence in Alzheimer’s Disease (ICARE AD) to measure real-world outcomes;
• A novel Alzheimer’s Disease Clinical Data Research Network (CDRN), modelled on approaches from other diseases, such as multiple sclerosis and oncology, to allow for broad data-sharing and comparative analyses; and
• Prospective studies of Medicare claims, to c understand utilization patterns (including demographic and geographic differences).

The CMS’ draft decision is also drawing criticism by other parties. US House Republicans, led by Congresswoman Cathy McMorris Rodgers (R-WA), the Ranking Member of the House Energy and Commerce Committee, directed a letter to US Health and Human Services (HHS) Secretary Xavier Becerra to abandon and re-propose the NCD to provide for reasonable access to FDA-approved Alzheimer’s treatments for a broader population of Medicare beneficiaries. More than 50 patient advocacy groups also directed a letter  to Secretary Becerra to direct the CMS to revise its draft NCD.

Source: Biogen, US Centers for Medicaid and Medicare Services, Ranking Member Rogers’ letter, and the Us Against Alzheimer’s letter