Novel Alzheimer’s drug stirs debate (again)

When the Food and Drug Administration last June gave its stamp of approval to Aduhelm, a novel drug for Alzheimer’s disease, the decision prompted a backlash. Three members of a drug advisory committee that questioned the drug’s effectiveness resigned — with one calling it “probably the worst drug approval decision in recent U.S. history.”

Now another bureaucratic ruling on Aduhelm is stirring disagreement. Earlier this month, the Centers for Medicare and Medicaid Services (CMS) severely limited access to the Alzheimer’s drug when it announced it would only provide Medicare coverage of Aduhelm for patients enrolled in approved clinical trials. Medical experts hopeful about the drug’s potential are disappointed by CMS’ decision, but others are relieved Medicare won’t be footing the bill for an experimental medication.

Aduhelm, made by Biogen and known by the generic name aducanumab, was shown in clinical trials to reduce the build-up of beta-amyloid plaque, a protein commonly found in dementia patients. These amyloid plaques are thought to be an underlying cause of Alzheimer’s disease, making Aduhelm the first drug targeted at halting Alzheimer’s progress rather than merely treating its symptoms. One year of Aduhelm infusions is currently priced at roughly $28,000.

The CMS decision limits Aduhelm coverage to a few thousand people out of the approximately 1.5 million Americans living with early-stage Alzheimer’s. Approved via the FDA’s accelerated approval pathway, Aduhelm must undergo additional clinical trials demonstrating its effectiveness before receiving full FDA approval. CMS stated in a press release that Medicare coverage of amyloid blocking drugs, including Aduhelm, would be widened if they receive full FDA approval.

Dr. Stephen Salloway, director of Butler Hospital’s Memory and Aging Program in Providence, R.I., had planned to offer Aduhelm to his patients with early Alzheimer’s. But without Medicare coverage, he predicts the 20 patients to whom he currently administers the novel therapy will have to discontinue it.

“With this decision, CMS has effectively taken away the ability of patients with a terminal illness and limited treatment options to weigh the risks and benefits of this new FDA-approved medication with their doctor and determine if it’s right for them,” Salloway wrote in a comment he submitted to Alzforum, an Alzheimer’s research website, and shared with me.

The FDA approved Aduhelm despite almost uniform dissension from the agency’s independent Peripheral and Central Nervous System Drugs Advisory Committee. Panel members were skeptical of the drug’s effectiveness, citing weak evidence from Biogen’s clinical trials. In March 2019, Biogen halted two large clinical trials examining the drug’s ability to slow cognitive decline in patients with early Alzheimer’s disease based on an independent research team’s predictions that the trials would not succeed. But in October 2019 Biogen claimed that further analysis of a larger data set revealed that patients receiving the highest dose of Aduhelm had a significant reduction in cognitive decline.

Salloway, who co-chaired the investigative steering committee for Aduhelm’s phase 3 clinical trials, acknowledged in an interview that existing data on Aduhelm is “incomplete and not straightforward.” But he had hoped Medicare would fund larger patient studies that could prove Aduhelm’s efficacy, rather than limiting coverage to those enrolled in clinical trials approved by CMS or the National Institutes of Health. He’d like to see access for all clinical trial patients who qualify, meaning all early Alzheimer’s patients who test positive for amyloid plaques. He plans to use the Alzheimer’s Association’s National Treatment and Diagnostic Alzheimer’s Registry to track long-term patient data that could show Aduhelm’s efficacy.

Dr. Robert Cranston, a neurologist at the Carle Foundation Hospital in Urbana, Ill., and a member of the Christian Medical and Dental Associations, agrees with CMS’ decision to limit Medicare coverage of Aduhelm. Cranston is skeptical of clinical trial evidence suggesting that Aduhelm works, and he also questions the idea that amyloid protein causes Alzheimer’s, noting previous studies have disputed this theory. He says he’s against taxpayer dollars funding the rollout of the high-priced drug.

“All of us [would be] paying for something that has some known bad side effects,” he said. “And there’s no real proven benefit.” (The side effects reported in Biogen’s phase 3 trials included MRI images suggestive of brain damage, as well as other side effects including headache, confusion, dizziness, and nausea.)

Peter Pitts, president of the Center for Medicine in the Public Interest, believes CMS overstepped the bounds of its authority when, during its review, it took the unusual step of disagreeing with the FDA’s approval process for Aduhelm. “CMS should not be in the position to second-guess FDA’s decision on approving a drug licensed for sale. That’s not their job,” said Pitts, who served as an associate commissioner of the FDA in the George W. Bush administration.

Pitts described the CMS decision as creating two standards of care, one for wealthier and one for poorer Americans. Only those with private health insurance will be able to afford Aduhelm, while those who rely on Medicaid will not.

He predicts the decision will discourage pharmaceutical companies from developing innovative drug therapies in the future. In not backing FDA approvals, he said, CMS is sending the message “don’t bother” to companies that would otherwise invest millions of dollars into novel treatments.

Such a lack of innovation will eventually catch up to everyone, not just poorer Americans, Pitts said: “You can’t access drugs that don’t exist.”