April 12, 2022 – Despite roughly 10,000 public comments and intense lobbying regarding a draft national coverage determination for the controversial Alzheimer’s drug Aduhelm, last week the Centers for Medicare and Medicaid Services (CMS) announced it will retain the proposal’s coverage plan: Medicare will only fund prescriptions of Aduhelm for patients enrolled in randomized, controlled clinical trials. This decision has a significant impact on drugs approved through the Food and Drug Administration’s (FDA’s) accelerated approval pathway, which Biogen used for Aduhelm.
“For the first time, CMS has made clear that FDA approval will not guarantee Medicare coverage,” said Coalition for Healthcare Communication Executive Director Jon Bigelow. “That presents a new challenge for many manufacturers hoping for drug approvals through the accelerated pathway. It is immediately relevant to Lilly, Genentech, Eisai, and other manufacturers that are now developing Alzheimer’s disease agents in the same class as Aduhelm — for which an estimated 85 percent of the patient population is covered by Medicare,” he said in a CHC Industry Alert.
There was one significant concession by CMS, Bigelow pointed out. In the draft proposal, CMS said the limits on coverage would apply to other drugs in the same class as Aduhelm. In the final decision, CMS said that if another agent in the same class shows clear evidence that it benefits patients with mild cognitive impairment (MCI), Medicare would cover it.
Accelerated approval pathway now riskier?
The CMS decision caps a tumultuous approval and post-approval period for Aduhelm (see related story, here). “It’s fair to say that last June’s approval of Aduhelm illustrated almost everything critics of the accelerated approval process have complained or warned about,” Bigelow noted.
The accelerated approval pathway is intended for drugs addressing serious diseases lacking effective treatments, and provides a way to market for a drug with an uncertain benefit but that affects a biological mechanism in a way that is reasonably likely to help patients. To date, 65 percent of approvals granted through this path have been in oncology, and some 42 percent in rare diseases; few, if any, have had a potential target population numbering in millions of patients likely to be treated for years, as in the case of Aduhelm.
According to the FDA, more than 250 drugs have initially been approved through its accelerated pathway since it was introduced in 1992 – including 28 percent of the 50 new molecular entities approved last year. So, this pathway has a significant impact on development of innovative medicines.
CMS stays the course
The cost of Aduhelm – initially set by Biogen at $56,000 for a year of therapy (plus significant additional expense for PET scans, MRIs, and infusion costs) – was later halved to $28,800 per year, but even at this level, Aduhelm threatened to cost Medicare as much as $15 billion to $20 billion per year by some estimates. The threat of this financial burden caused CMS to hike annual Medicare premiums for seniors by a remarkable 15 percent for 2022.
In the end, CMS reaffirmed that it will limit Medicare coverage for Aduhelm to the relative handful of patients in clinical trials that are approved by the FDA or National Institutes of Health, not the millions of seniors with MCI. It made a few minor changes in its rule to allow a broader definition of the acceptable clinical trials, but it also stipulated that to be covered, a patient must have evidence of amyloid plaques, the reduction of which was the surrogate endpoint of the Aduhelm trials.
CMS Administrator Chiquita Brooks-LaSure said “the vast majority” of the public comments CMS received were in favor of limiting coverage. However, at least 78 members of the House and two senators wrote to CMS opposing the proposal. There also was vigorous lobbying against those limits from Alzheimer’s disease advocacy groups, biopharma companies, and the Pharmaceutical Research and Manufacturers of America (PhRMA).
PhRMA issued the following statement on CMS’s action: “This decision sets the dangerous precedent of restricting Medicare Part B coverage and patient access for new and future FDA-approved medicines for patients with Alzheimer’s disease. CMS has further complicated matters by taking the unprecedented step of applying different standards for coverage of medicines depending on the FDA approval pathway taken, undermining the scientific assessment by experts at FDA. We hope the Administration reconsiders this policy immediately.”
Although the CMS decision applies only to Medicare patients, private insurers may choose to follow CMS’ lead. While awaiting the CMS decision, many insurers declined to cover Aduhelm therapy.
For now, members of Congress are seeking greater scrutiny of the FDA’s accelerated approval process, and may tie related legislation to the Prescription Drug User Fee Act (PDUFA VII) (see related story, here). FDA Commissioner Robert Califf, M.D., has promised to review how the accelerated approval pathway is implemented.