Biogen Alzheimer’s disease drug Aduhelm secured its FDA approval on less clinical data than is typically required, so the Center for Medicare and Medicaid Services has chosen a coverage pathway that will enable it to gather more evidence. The agency on Tuesday proposed covering the drug only for those participating in qualifying clinical trials.
By law, CMS covers items and services deemed reasonable and necessary. When there isn’t enough data to determine whether something meets those criteria, the law has a provision that permits limited coverage. “Coverage with evidence development” is a mechanism that enables CMS to cover a drug in the context of a clinical study that generates additional data that could support a broader coverage decision. CMS’s proposal of this pathway for Aduhelm is preliminary, but it applies to all therapies in its drug class. A final CMS decision is expected on or before April 11. In the meantime, the matter is open to public comment for the next 30 days.
Aduhelm is antibody designed to reduce beta amyloid plaques that build up in the brains of Alzheimer’s patients. Phase 3 tests of the drug produced mixed results about how well the drug worked. In addition to offering unclear patient benefit, the drug also comes complication risks, some that are potentially fatal. But rather than asking the Cambridge, Massachusetts-based company to conduct another clinical trial, the FDA last June granted the drug accelerated approval. Such decisions are based on a surrogate endpoint, an indication that a drug might be working. Benefit of the drug must be demonstrated in post-marketing studies, which Biogen plans to begin later this year.
The proposed CMS decision notes that to date, no clinical trial of an amyloid-targeting antibody drug has shown clinically meaningful improvement in cognition and function in Alzheimer’s patients, and “there is insufficient evidence to conclude that use of monoclonal antibodies directed against amyloid is reasonable and necessary for the treatment of Alzheimer’s disease.” CMS further points out that the conclusion of statistical significance in one of the two pivotal studies was reached only with a post-hoc analysis of the data; a secondary analysis of patients at the high dose of the drug raised questions about the reliability of the clinical trial results. The agency also noted the safety risks of the drug, which is associated with amyloid-related imaging abnormalities (ARIA), bleeding and swelling in the brain detected on MRI scans.
“Due to the lack of a clear clinical benefit and the frequency of adverse events like ARIA, the evidence does not support that the benefits outweigh the harms for (monoclonal antibodies) directed against amyloid for the treatment of (Alzheimer’s disease),” the proposed CMS decision states. “Adverse events are more closely monitored and treated in the context of a clinical trial compared to general practice. We have additional concerns at this time about harms in patients that would be treated outside the context of the safety monitoring of a controlled trial.”
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
CMS’s proposal to cover Aduhelm only for participants is a limiting one, but it’s not without precedent. The agency has issued coverage with evidence development decisions in the past. Stem cell transplants for blood disorders and cochlear implants are among the products that received such determinations. Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation, said that the CMS proposal is appropriate and consistent with the FDA’s accelerated approval decision based on limited data.
“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real world populations,” Fillit said in an emailed statement. “This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment.”
Questions about Aduhelm’s benefit surrounded the drug before the FDA approved it, and they continue now. Prescriptions of the new drug have been slow. Last month, Biogen slashed the drug’s $56,000 annual wholesale price in half in an effort to boost sales. If the CMS proposal to cover Aduhelm only for those in a clinical trial is finalized in April, the pool of covered patients will continue to be a small one. CMS won’t be conducting the clinical studies to gather more evidence on Aduhelm. An entity that would like to conduct a clinical trial would submit a proposal to the agency for approval. But as long as the study meets CMS criteria, the agency would cover Aduhelm for participants in the studies. Depending on the results of these studies, CMS can revisit its coverage decision for the drug.
Photo: Adam Glanzman/Bloomberg, via Getty Images
