For decades, Alzheimer’s sufferers have struggled with a debilitating disease without the prospect of a treatment that could slow the disease’s relentless advance.
Such a drug seemed on the cards when U.S. regulators approved Biogen’s Aduhelm last year. Competitors Eli Lilly and Eisai of Japan are pushing ahead with clinical trials for similar treatments and said they would also apply for accelerated approval from the Food and Drug Administration.
But the future of this new class of drugs for a disease that affects up to 50 million people worldwide faces a difficult path to widespread acceptance after the agency that controls spending by federally funded health care systems in the US imposed strict restrictions on has imposed the financing of the drugs.
The Centers for Medicare & Medicaid Services issued a formal decision Thursday to limit reimbursement for Biogen’s drug to just a few thousand patients participating in clinical trials, rather than the estimated 6 million people with Alzheimer’s in the United States.
His decision hurts Biogen because most Alzheimer’s patients are older and are therefore covered by the federally funded Medicare program for people age 65 and older. The biotech group had previously announced $500 million in cost cuts after publishing a draft decision in January that anticipated restrictions on the drug, which is priced at $28,000 per patient per year.
The agency, which has broken the convention of funding FDA-approved drugs, cited the treatment’s “harm potential,” which ranges from headaches to cerebral hemorrhage, and concerns about its effectiveness.
The decision applies not only to Aduhelm, the first drug for Alzheimer’s approved since 2003, but also to other drugs in development based on the “amyloid hypothesis”. The theory goes that the disease is caused by the buildup of a sticky plaque called beta-amyloid in the brain.
CMS said similar drugs approved under the FDA’s accelerated approval process would be subject to the same restrictions as Aduhelm.
However, in a softening of its draft decision in January, the agency said treatments that were approved through the FDA’s standard approval process and showed evidence of clinical benefit would be covered for patients under Medicare without enrollment in a clinical trial.
“This long-term path is designed to be flexible and responsive to any new drugs in this class that are in the pipeline and demonstrate clinical benefit,” said Lee Fleisher, CMS chief medical officer.
The pharmaceutical industry lashed out at CMS after its draft proposal, warning that such restrictions threatened to delay treatment and prevent early detection of Alzheimer’s. It also said the move would have a “dissuasive effect” on research by companies developing novel drugs.
“It is truly unprecedented what CMS has done to suggest that you may not offer coverage for. . . an FDA-approved drug,” said Anne White, President of Lilly Neuroscience, in an interview shortly before the agency made its final decision. “This is a concern you’re hearing not only from us, but from others in the field.”
Biogen had warned that if CMS didn’t change its initial decision, most patients would have to wait up to five years for Aduhelm to become more widely available. By then, many of them will have progressed to a more severe stage of the disease and would not benefit from the drug, she added.
“She [CMS] can draw inspiration from what has been done in the case of cancer. We had more than 200 drugs that received accelerated approval, giving patients and their physicians a choice,” said Chirfi Guindo, an executive at Biogen.
The draft decision of the CMS has prompted companies to reconsider whether it is worth applying for accelerated approval. In February, Lilly said it would delay donanemab’s application for accelerated approval, which was expected before late last month.
Rachelle Doody, Global Head of Neurodegeneration at Roche, said in an interview that the company would not seek accelerated approval for its candidate gantenerumab. It will instead follow the FDA’s regular approval path, which means it will have to await the results of a late-stage study due later this year.
Drug manufacturers are threatened with a loss of sales in the billions. Analysts at BMO projected that if approved, donanemab would generate nearly $5 billion in annual sales by 2028. According to consensus estimates from last year, Aduhelm was expected to hit $9 billion in peak annual sales at some point.
Many Alzheimer’s researchers defend the CMS decision and are deeply skeptical about the FDA’s move to accelerate the approval of Aduhelm. The drug agency concluded that the drug could only predict clinical benefit “with a reasonable degree of probability” and said more studies were needed to be certain.
“[This] is probably the worst drug approval decision in recent U.S. history,” said Aaron Kesselheim, a professor at Harvard Medical School. He was one of three members of a committee advising the FDA on the drug Leave in protest of the agency’s approval.
Critics say there is little conclusive evidence that clearing amyloid plaques slows the development of Alzheimer’s and warn the FDA decision could set a damaging precedent.
“This approval was reckless and dangerous. It’s lowered the standards for approving drugs for Alzheimer’s disease, and that’s why there’s a rush from companies targeting beta amyloid in the brain,” said Michael Carome, director of health research at Public Citizen, a progressive think tank.
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But Alzheimer’s support groups are concerned that some patients, particularly minorities and those in rural areas, are being disadvantaged because they are less likely to be enrolled in clinical trials.
Last month, USAgainstAlzheimer’s, an advocacy group, launched a television ad to campaign against the CMS draft decision, while a group of 74 congressional Republicans sent a letter to the Joe Biden administration urging them to “abandon and repurpose” the decision “.
Dewayne Nash, a former family doctor who was diagnosed with Alzheimer’s, said the FDA probably should have waited for more conclusive data before approving Aduhelm. But he now said that the drug was approved and that CMS should pay for it.
“Alzheimer’s is like terminal cancer. People are willing to take experimental drugs to slow things down, to buy some family time, to gain six months, a year or two,” said Nash, who is participating in a clinical trial with Aduhelm.