The Centers for Medicare and Medicaid Services (CMS) issued on Thursday its hotly debated final decision on whether to cover aducanumab (Aduhelm), the first FDA-approved treatment for Alzheimer’s that slows the disease’s biological progression rather than just temporarily easing its symptoms. We believe it made the wrong choice.
The agency, which regulates the public insurance programs that collectively serve about 135 million Americans, decided it will cover the cost of Aduhelm only for the tiny subset of people with early-stage Alzheimer’s disease who choose to enroll in CMS-approved clinical trials of the drug.
In practical terms, the decision means that Aduhelm will be off limits to all but a few thousand people — a fraction of the roughly 1.5 million Americans with early-stage Alzheimer’s who would have otherwise qualified to take the medicine based on the FDA’s approval in June 2021. When the FDA approves a medication, CMS almost invariably covers it, with private insurers routinely following suit.
As physician-scientists who have been researching Alzheimer’s disease and treating people with it for decades, we find the science behind Aduhelm convincing — and CMS’s unprecedented decision highly disappointing.
Fortunately, CMS backed off one of the worst elements of its original draft decision. In January, it had initially proposed a Medicare coverage policy that would have severely restricted access not just to Aduhelm but also to any future drugs in the same therapeutic class: monoclonal antibodies targeting harmful protein deposits in the brain known as amyloid plaques. In essence, the agency was planning to prejudge an entire category of medicines before data about them are in.
But after considerable pushback from patient groups, scientists, physicians, and others, CMS revised its original plan. In its final decision, the agency telegraphed that it is open to covering future amyloid antibody therapies that deliver significant clinical benefits and receive conventional FDA approval.
That’s good news for people with Alzheimer’s and their loved ones, because these monoclonal antibodies — three of which are in the third and final phase of clinical trials — show substantial promise based on earlier trial data.
The controversy around Aduhelm and related antibodies stems from a debate about whether clearing amyloid plaques slows the progression of Alzheimer’s. In the past two decades, several approaches targeting amyloid in the brains of Alzheimer’s patients failed in clinical trials. Some scientists concluded that such approaches were doomed to be ineffective. None of those earlier agents, however, was shown to decrease amyloid plaques!
That changed in the last three years. Aduhelm and three other amyloid antibodies have been shown to robustly lower amyloid levels in the brain, and most showed evidence of slower cognitive decline. Also important to note is that the clearing of amyloid was followed by reductions in excess tau protein, another major brain change seen in people with in Alzheimer’s. Aduhelm was the first therapeutic agent that lowered both of these hallmarks of Alzheimer’s disease.
Critics have questioned the FDA’s approval of Aduhelm because only one of its two final trials was successful without acknowledging that the two trials were not identical. The successful trial had more participants who received a higher total dose of Aduhelm over time. Yet participants’ in the “failed” trial who received high total doses — like those in the successful trial — also experienced a slowing of mental decline. When combined with the significant lowering of brain amyloid in both trials, these compelling findings led the FDA to grant the drug accelerated approval.
CMS officials disagree with the FDA’s reasoning, and are likely worried about the cost of covering a medication for hundreds of thousands of beneficiaries who might seek the treatment if it was broadly covered by Medicare. While CMS’s concern for taxpayers is understandable, it’s the FDA — not CMS — that has the statutory authority and deep medical expertise to assess a drug for approval. And Aduhelm passed the FDA’s assessment.
CMS arguably overstepped the bounds of its authority. Its decision is a huge blow to millions of Americans living with Alzheimer’s and their families. They are the losers in CMS’s decision, not only from the severe restriction on access to Aduhelm but also from its chilling effect on the development of other disease-modifying agents for people with Alzheimer’s. If CMS won’t pay for a treatment after the FDA legally approves it, why should a company bother pursuing this pathway?
CMS’s decision will affect the exploration for new treatments for Alzheimer’s for years, just at the time when new drugs appear to be making progress against this terrible disease.
Dennis J. Selkoe is a neurologist, co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston, and a professor of neurologic diseases at Harvard Medical School. Jeffrey Cummings is a neurologist, professor of brain sciences, and director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas.