Professor Calls for Alzheimer’s Drugs REMS
University of Pennsylvania Perelman School of Medicine professor of medicine, medical ethics and health policy, and neurology Jason Karlawish says FDA should require a Risk Evaluation and Mitigation Strategy (REMS) for new Alzheimer’s disease drugs to mitigate the concern of Alzheimer’s clinicians that some patients will be needlessly harmed by the drugs. In a detailed Stat News opinion online column, Karlawish reviews the benefits and risks of Eisai’s lecanemab and Lilly’s donanemab, anti-amyloid antibody drugs that are likely to be approved by FDA soon.
He says the concerns he and other specialized Alzheimer’s clinicians have are less with the drugs themselves, whose benefits and risks are reasonably well known, and more with the healthcare system in which they will be used.
“Here’s my worry as an Alzheimer’s expert practicing at a memory center,” he writes. “In the months after the drugs are approved, news organizations will recount the sad stories of patients who received a prescription that was neither reasonable nor necessary. They were prescribed the drugs following sloppy diagnoses and went on to suffer risks that weren’t properly mitigated. Skeptics will gesture to aducanumab (Biogen’s Aduhelm) and parade these stories as further evidence that anti-amyloid drugs ‘don’t work’ or are ‘too risky’ and so a waste of Medicare resources. I also worry about the patients who could have benefited from the drugs but were misdiagnosed. They won’t make the news, but they’re another example of the unfortunate outcomes of multiple converging circumstances that threaten to wreck the progress we’ve achieved.”
He discusses the problems he sees with diagnoses, risks associated with identifiable patient characteristics, and the difficulty of measuring a positive treatment effect for the drugs.
“At heart, we have a numbers problem here,” Karlawish writes. He says hundreds of thousands and perhaps millions of Americans could be taking the drugs and cites a 2017 RAND report warning that “the U.S. healthcare system is ill-prepared to handle the potentially high volume of patients who would be eligible for treatment.”
Summing up, he says the workup of mildly symptomatic presentations of memory loss is tricky and time-intensive, biomarker testing carries nuance, the drugs’ risks can be serious and are associated with a gene for Alzheimer’s disease and may be heightened in persons on anti-coagulants and cerebral amyloid angiopathy, the measures of value are difficult to translate into clinical practice and policy, Medicare wants patients enrolled in a registry, the drugs’ costs are notable, and there are lots of patients and not enough clinicians to accurately diagnose and treat them. Finally, he says, the risks are vivid and they happen within the first few months of treatment, while the benefits of disease slowing are far less evident.
While there are technological solutions that can address some of the issues, Karlawish writes, they will require changes to laws and regulations.
He sees the imposition of a REMS as a solution that can happen right now. He lists the many items that could be included in a REMS requirement and concludes that with a REMS in place, “we’ll have confidence and trust that the system did its best with the resources we have, and we’re learning to do even better.”