Lilly and Roche push back on draft CMS guidelines on Aduhelm

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United States Medicare and Medicaid Service Centers (CMS) has just completed the open comment period for their national coverage draft decision for Biogen’s Alzheimer’s drug Aduhelm (adacanumab).

The guidelines were very broad, with the agency saying they would only cover the cost of biogenic‘s Aduhelm and all required scans “if enrolled in eligible clinical trials”. These trials should “demonstrate a clinically significant benefit on cognition and function”.

Significantly more problematic, CMS proposed to apply these guidelines to all drugs in this class. Aduhelm is a monoclonal antibody that eliminates beta-amyloid, a protein that accumulates abnormally in the brains of patients with Alzheimer’s disease. Although beta-amyloid is a factor in the disease, it is not entirely clear that its removal improves cognition and memory, although some evidence suggests that it does. When this was announced, many biopharmaceutical companies and industry watchers expressed concern that it was too broad and would negatively impact the industry, especially companies currently developing anti-amyloid drugs.

Two of the other major players in the field have now voiced their criticism of this direction. As part of Eli Lilly’s fourth quarter and full year financial reportthe company indicated that its timeline for an accelerated approval request for its own Alzheimer’s disease drug, donanemab, was no longer on schedule for the first quarter after the draft CMS guidelines.

Eli Lily had started a rolling submission of the drug in October 2021, with plans to complete it in this first quarter of 2022. However, due to questions on the proposed CMS policy, they suggested delaying the submission until that they have a final reading of the Trailblazer 2 Phase III studies, which are not expected until 2023.

In the open comments section, Lilly wrote, “We urge the Centers for Medicare & Medicaid Services to cover new monoclonal antibodies against amyloid plaque for the treatment of Alzheimer’s disease upon Food and Drug Administration approval for populations studied in their positive registration trials. Subsequent changes in covered patient populations may be based on changes in FDA-approved labeling or on evidence in published peer-reviewed studies.

Lauren Neves, Assistant Vice President of PhRMA, a biopharmaceutical industry trade organization, also wrote in support of the class of drugs, saying: “We urge CMS to ensure that any NTMs developed for this particular class of drugs (i.e. monoclonal antibodies against amyloid for the treatment of Alzheimer’s disease) remains flexible enough to accommodate a range of reasonable and necessary treatment options that are available and may become available in the future. For example, insofar as it considers national coverage policy, the CMS will need to consider potential differences in medicines and the clinical research that supports them, including the patient population targeted, the endpoints of study and/or associated diagnoses.

Genentecha rock company, expects a readout of vital data on its own anti-amyloid drug, gantenerumab, in the second half of 2022. It also has another drug in development, crenezumab. In a statement, David Burt, Executive Director of Federal Government Affairs for Genentech, said, “We believe that by including anti-amyloid therapies still in Phase III clinical trials under this policy, CMS compromises individuals’ access to products that may be approved in the future and that may suit their specific treatment needs, without even considering the evidence of those products.

Additionally, Genentech argues that limiting coverage of these drugs outside of the clinical trials they approve limits the potential for real evidence, an increasingly important modality for generating clinical data.

In the comments section, the responses vary widely. For example, Kevin Schulman, professor of medicine at Stanford University, noted that he and his team published an article in JAMA on July 19, 2021, which reviewed Aduhelm and concluded that it “is not reasonable and necessary given the clinical evidence and the unfavorable risk-benefit profile”.

However, Ronald Peterson, professor of neurology at the Mayo Clinic, wrote: “As the inaugural chair for six years of the HHS Advisory Council on Research, Care and Services for the US National Plan to address Alzheimer’s Disease, I am acutely aware of the main objective of the national plan which is to develop therapies for Alzheimer’s disease by 2025. Although aducanumab is not a cure for the disease, it offers the possibility of treating one of the main components defining Alzheimer’s disease, amyloid. As such, we need to provide CMS coverage to our patients to assess the clinical effectiveness of the drug as outlined in the plan. CMS populations need the opportunity to evaluate disease-modifying therapy. »

Another twist is that 47 House Republicans signed a letter against the plan to determine coverage, arguing that CMS was proposing to restrict access to a drug that has “already been approved by the FDA as safe and effective” and that the agency appeared to question the “expertise and authority” of the FDA.

In its own comments, Biogen defended the drug and outlined a three-pronged plan to generate real-world evidence that would complement rather than duplicate existing clinical trials and address CMS’s remaining issues with the drugs. They included:

#1. “A targeted registry, such as the International Collaboration for Real-World Evidence in Alzheimer’s Disease (ICARE AD) to measure real-world outcomes.”

#2. “A new Alzheimer’s Disease Clinical Data Research Network (CDRN), inspired by approaches from other diseases such as multiple sclerosis and oncology to enable broad data sharing and comparative analyses.”

#3. “Prospective studies of health insurance claims, to better understand usage patterns (including demographic and geographic differences).”

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