Medicare will only cover Aduhelm for patients enrolled in clinical trials

CMS announced that Medicare is limiting coverage of the controversial Alzheimer’s disease drug Aduhelm to participants who are enrolled in FDA- or NIH-approved clinical trials.

The decision was based on a review that included comments from more than 10,000 stakeholders and more than 250 peer-reviewed documents, CMS said. It is specific to patients who are clinically diagnosed with mild cognitive impairment due to Alzheimer’s disease or mild dementia and a confirmed presence of plaque on the brain.

“I think Medicare made the right decision. It’s pretty clear that the science regarding aducanumab is murky at best,” G. Caleb Alexander, MD, MS, founding codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins Bloomberg School of Public Health and principal investigator of the Johns Hopkins-FDA Center of Excellence in Regulatory Science and Innovation, told Healio.

Aduhelm (aducanumab, Biogen/Eisai) is the only FDA-approved monoclonal antibody directed against amyloid beta for the treatment of Alzheimer’s disease. It received accelerated approval in June 2021.

Under the accelerated approval strategy, a drug is approved based on its effect on a surrogate marker of disease, which in this case is beta-amyloid levels in the brain, according to a previous paper by Alexander and Jason Karlawish, MD, a professor of medicine in the division of geriatrics at the Perelman School of Medicine at the University of Pennsylvania. This is in comparison to drugs that receive FDA approval based on clinical outcomes, such as the signs or symptoms of Alzheimer’s disease.

In the case of aducanumab, Alexander said the FDA granted accelerated approval despite the lack of evidence demonstrating its efficacy and the value of amyloid alone as a valid surrogate for treatment.

“In this instance, you not only have a questionable surrogate in amyloid, but you also have well-designed, appropriately powered clinical trials examining clinical endpoints that failed to demonstrate convincingly substantial evidence of effectiveness,” he said. “This wasn’t a typical accelerated approval.”

According to Alexander, it was a wise decision for Medicare to cover aducanumab solely “in the context of generating further evidence” on its efficacy.

“The bottom line is that it’s completely unclear whether or not the product even works,” he added. “The main thing that’s clear about the product is that it has significant safety concerns, but whether or not it’s efficacious is anybody’s guess.”

Future monoclonal antibodies directed against amyloid that receive traditional FDA approval may be available in additional settings for Medicare beneficiaries participating in CMS-approved studies, “such as a data collection through routine clinical practice or registries,” CMS said. Other drugs in this class that receive accelerated approval or have not been determined by the FDA to demonstrate a clinical benefit will only be covered in the setting of FDA- or NIH-approved trials.

Biogen released a statement claiming the “unprecedented CMS decision effectively denies all Medicare beneficiaries access” to aducanumab and may limit coverage of future FDA-approved drugs in the same class.

“These coverage restrictions, including the distinction between accelerated approval and traditional approval, have never been applied to FDA-approved medicines for other disease areas,” the company said. “Biogen is carefully considering its options and will provide updates as the company further evaluates the business impact of this decision.”

Meanwhile, CMS said it will continue monitoring future developments in this drug class “and is committed to continuing to explore ways to improve care for people with Alzheimer’s disease.” 

“Science, evidence and stakeholder input led our team of career civil servants and clinicians through this national coverage determination process,” Lee Fleisher, MD, the chief medical officer at CMS and director of the Center for Clinical Standards and Quality, said in a press release. “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.”

References:

Alexander GC, et al. Ann Intern Med. 2021;doi:10.7326/M21-2603.

Biogen’s statement on the final national coverage determination for amyloid-beta targeting therapies for the treatment of Alzheimer’s disease. https://investors.biogen.com/news-releases/news-release-details/biogens-statement-final-national-coverage-determination-amyloid. Published April 7, 2022. Accessed April 8, 2022.

CMS finalizes Medicare coverage policy for monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease. https://www.cms.gov/newsroom/press-releases/cms-finalizes-medicare-coverage-policy-monoclonal-antibodies-directed-against-amyloid-treatment. Published April 7, 2022. Accessed April 8, 2022.