On January 11, 2022, the Centers for Medicare and Medicaid Services (“CMS”) published an anticipated proposed National Coverage Determination (“NCD”) decision memorandum that begins the process of determining whether the Medicare program will cover FDA-approved monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s Disease. (https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&NCAId=305).
The proposed decision, which is subject to public comments that are due to CMS by February 10, 2022, does not endorse nationwide Medicare coverage for these drugs. Instead, CMS chose an alternate pathway known as Coverage with Evidence Development (“CED”). If the proposal is adopted by CMS, it would set in motion a detailed regulatory process that includes temporary Medicare coverage for the drug but only for certain Medicare beneficiaries who are enrolled in an additional clinical trial intended to test whether these drugs will have a significant benefit for Medicare beneficiaries. CMS expects to issue a decision by April 11, 2022 to approve or reject the CED process after reviewing comments from interested parties.
Monoclonal Antibodies as a Potential Alzheimer’s Treatment
Alzheimer’s Disease is a progressive neurologic disease that causes brain cells to atrophy and die. It afflicts approximately 5.8 million people in the United States. Approximately 95% of all cases occur in individuals over age 65, and its incidence is expected to rise steadily over time. It is the sixth leading cause of death in the United States. The exact cause of Alzheimer’s is not known, but it is characterized by the formation of amyloid protein plaques that disrupt the normal functioning of neurons in the brain.
In 2021, the FDA approved the first anti-amyloid monoclonal antibody drug, Aduhelm, which is intended to trigger a response by the patient’s own immune system that destroys the accumulation of amyloid plaques. The FDA approval was not without controversy: the FDA’s own advisory panel had concluded that there was insufficient evidence that the drug worked as intended and recommended against approval. After the FDA approval, several large medical centers stated that they would not be administering Aduhelm due to concerns about its efficacy.
What Happens Next?
The FDA’s determination does not mandate Medicare coverage for Aduhelm. CMS has proposed to cover Aduhelm or any other anti-amyloid monoclonal antibody drug only for those Medicare beneficiaries with mild cognitive impairment due to Alzheimer’s or mild Alzheimer’s dementia and who have evidence of amyloid plaques and who enroll in a multi-center clinical trial that either incorporates specific CED criteria established by CMS and is approved by CMS, or is sponsored by the National Institutes of Health (“NIH”). Medicare beneficiaries would not be eligible to enroll in the trial if they have any other cognitive deficits or other medical conditions that are likely to result in significant adverse events or death.
The purpose of any clinical trial would be to evaluate the health outcomes of Medicare beneficiaries diagnosed with Alzheimer’s, focusing on changes in the decline of cognitive function and any adverse events associated with these new drugs. All CED trials would have to be conducted through hospital outpatient departments. The Medicare Part B program would not cover the drugs in any other setting.
If CMS finalizes this NCD proposal, then the drug’s manufacturer and other investigators would have to design a clinical trial that either meets specific CED criteria set out by CMS or is supported by NIH. CMS noted that the trial design should seek data that is applicable to the entire Medicare population; in particular, CMS noted that incidence of Alzheimer’s varies among racial and ethnic groups, and CMS has instructed that any trial population should reflect the national distribution of Alzheimer’s diagnoses. CMS would have access to all of the clinical trial data as a condition of Medicare coverage. Any approved CED trial could take up to several years to complete depending on factors such as enrollment, the quality of data needed, and agreed-upon clinical endpoints.
At the conclusion of the clinical trial, CMS would then analyze the CED trial data and decide whether to propose that the Medicare program cover the drug nationwide, and if so, any conditions under which the drug would be covered. As a result, even after a trial is completed, CMS could still determine that coverage would be approved for only a subset of Alzheimer’s patients or deny coverage. That decision would also be subject to a public notice-and-comment period before CMS can publish a final NCD addressing nationwide coverage terms.
Any decision by CMS to begin the NCD process is an important event. Nevertheless, there are multiple hurdles that must be cleared before any drug in this category can be covered for the general Medicare population. Given the attention that has been drawn to this particular drug and the illness it is intended to treat, those hurdles may be challenging.
 Pam Belluck, Cleveland Clinic and Mount Sinai Won’t Administer Aduhelm to Patients, N.Y. Times (July 14, 2021)(https://www.nytimes.com/2021/07/14/health/cleveland-clinic-aduhelm.html?searchResultPosition=11).