As finalized in Thursday's National Coverage Determination (NCD), the decision follows draft proposals issued in January: putting the emphasis of coverage on proven clinical benefit. The CMS reviewed over 10,000 comments on the draft proposals, as well as 250 peer-reviewed documents.
Calling it an ‘unprecedented decision that effectively denies all Medicare beneficiaries access to Aduhelm’, Biogen is calling on the CMS to reconsider its decision once more data is published.
CMS: 'There is not currently enough evidence of demonstrating improved health outcomes to say that it is reasonable and necessary for people with Medicare'
Over 6 million older Americans are believed to have Alzheimer’s Disease, and this prevalence is expected to rise to 14 million by 2060 without the development of effective interventions.
Aduhelm is a monoclonal antibody directed against amyloid beta: with the accumulation of amyloid beta plaques in the brain a defining pathophysiological feature of Alzheimer’s disease. Accelerated approval was granted after clinical trials showed the effect of Aduhelm on reducing amyloid beta plaques.
While Biogen says the reduction of amyloid beta plaques is a surrogate biomarker ‘reasonably likely to predict clinical benefit, in this case a reduction in clinical decline’, the clinical benefit of the drug remains questioned with the FDA requiring a Phase 4 trial in this respect. (Europe's EMA, meanwhile, chose to decline the drug's marketing application party because the link to clinical benefit 'had not been established').
Consequently, the CMS says that given the ‘early but promising evidence’ – and need for effective treatments - its policy ‘will help answer whether the class of drugs improves health outcomes for patients’.
For drugs that 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 (NIH) approved trials. This applies to Aduhelm, which was approved under the accelerated approval pathway.
Meanwhile, Medicare says it will cover monoclonal antibodies that target amyloid (or plaque) for the treatment of Alzheimer’s disease that receive traditional approval from the FDA under coverage with evidence development (CED). Any new drugs in this class that receive FDA traditional approval may be available in additional care settings that people with Medicare can use, such as an outpatient department or an infusion center.
“There is the potential for promise with this treatment; however, there is not currently enough evidence of demonstrating improved health outcomes to say that it is reasonable and necessary for people with Medicare, which is a key consideration for CMS when making national coverage determinations,” said Dr. Lee Fleisher, CMS Chief Medical Officer and Director of the Center for Clinical Standards and Quality.
“In arriving at this final decision, we looked at the very unique circumstances around this class of treatments and made a decision that weighed the potential for patient benefit against the significance of serious unknown factors that could lead to harm. If a drug in this class shows evidence of clinical benefit through the traditional FDA approval process, then CMS will provide broad access and ensure the results from the rigorous trials are generalizable for people with Medicare participating in a CMS-approved study, such as a registry.
"Lastly, we structured this decision to provide flexibility and assurance that CMS can respond quickly to providing coverage for any new drugs in this class when a clinical benefit is determined.”
Biogen promises further data
Biogen says these coverage restrictions – including the distinction between accelerated approval and traditional approval – have never been applied to FDA approved medicines in other disease areas.
“When additional data from this new class of treatments become available, Biogen urges CMS to reconsider today’s decision for all FDA-approved amyloid-beta targeting therapies,” says a statement from the company.
“Biogen is carefully considering its options and will provide updates as the company further evaluates the business impact of this decision.”
With the drug already suffering from a disappointing uptake, a rejected application for authorization in the EU, and uncertainty over CMS coverage, Biogen has already halved its price and started cost-cutting measures across the company including layoffs.
Next up: lecanemab
Meanwhile, lecanemab – another monoclonal antibody for Alzheimer’s Disease – is being studied in a Phase 3 study with a readout expected in the fall (Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority).
Eisai has initiated FDA filing via the accelerated approval pathway. In a statement responding to the CMS' announcement, the company said: "Eisai believes Clarity AD has a robust design, which could meet the “high level of evidence” criteria set forth by CMS in the NCD decision memo if the result is positive; therefore, creating the potential for CMS to reconsider full coverage of lecanemab should it be approved by the Food and Drug Administration. We look forward to engaging constructively with CMS to ensure appropriate Medicare beneficiaries have access to this potential new therapy."
