Widespread access to the Alzheimer’s drug lecanemab from
The Centers for Medicare & Medicaid Services indicated it would consider covering lecanemab for Medicare patients, including those outside clinical trials, after the Food and Drug Administration approved it earlier this month.
The drug delays the progression of Alzheimer’s disease, though only modestly, a trial found. Lecanemab works by removing toxic brain deposits of a protein called amyloid.
The potential for CMS to make a national coverage change would mark a win for patient advocacy groups that have been pushing for Medicare to expand its current position of only covering this class of drugs for patients in clinical trials. It further underscores how much power the nation’s largest payer yields in accessing the drug even after it comes to market, and how these decisions may shift drugmakers’ strategies going forward.
The CMS issues national coverage determinations to set policies of the items and services it will cover and under what circumstances. Absent a national policy, Medicare relies on local contractors to make ad hoc coverage determinations.
“Medicare, for any medical product, could push for a national coverage determination or a coverage with evidence development, which would effectively curtail access to a product,” Anand Shah, a former FDA deputy commissioner and former CMS chief medical officer, said. “It would behoove medical product developers to take into account both agencies upfront, a priori, during development.”
Pharmaceutical companies already interact regularly with FDA regulators and need to start engaging more frequently and earlier with Medicare, Shah said. “Otherwise, we’re going to have continued phenomenon of clinical trials being designed with regulators in mind, but then having to conduct additional studies to fulfill the criteria of payers.”
Medicare’s coverage decision only applies to lecanemab, which is marketed under the brand name Leqembi, and Biogen’s aducanumab, which is sold under the brand name Aduhelm, for now, but the pipeline is growing.
The CMS said in a statement after the FDA’s approval that the drug falls under its 2022 national coverage determination for FDA-approved monoclonal antibodies directed against amyloid plaque in the brain for the treatment of Alzheimer’s disease. Under this policy, the CMS only covers these therapies for patients in approved clinical trial settings.
The CMS decision came after the controversial approval of Biogen’s other Alzheimer’s drug, Aduhelm, to better determine if amyloid reductions are adequate predictors of slowed Alzheimer’s progression.
The FDA allows drugs to come on the market if they’re safe and effective, while the CMS will pay for medicines it deems reasonable and necessary. If lecanemab eventually gets traditional approval, the CMS would allow for broader coverage for patients enrolled into a registry. This would allow for fewer restrictions than in controlled trial settings, but the treatment wouldn’t be as widely available as most other drugs approved under the FDA’s traditional pathway.
“The evidence requirement is motivated by CMS’ need to dispel uncertainties about how well these drugs work in the real world, which remains unclear,” said Anna Kaltenboeck, head of the Drug Pricing Practice team at health-care research firm ATI Advisory.
Not a ‘Slam Dunk’ Drug
The manufacturers of lecanemab are aiming for a traditional drug approval in the coming months based on data from a confirmatory trial showing that it reduced the pace of cognitive decline in people with early Alzheimer’s disease by 27% over 18 months. That study also showed risks of serious side effects, such as brain swelling and bleeding.
But the FDA’s approval Jan. 6 stemmed from an earlier study, known as a phase 2 trial, that had promising results in patients with mild cognitive impairment or mild Alzheimer’s, University of Pennsylvania bioethicist Holly Fernandez Lynch noted. While the phase 2 trial showed a clear reduction in amyloid, it missed the primary measurement of whether the treatment worked. And if the FDA grants traditional approval, it will be based on one positive study of a surrogate endpoint and one positive study of a clinical endpoint, similar to Aduhelm, she said.
“This is not the slam dunk drug some are making it out to be,” Lynch said. “Aducanumab set a very low bar, we shouldn’t forget that.”
While the final lecanemab trial results are promising, existing research still lacks clear answers on the long-term clinical benefit of amyloid-targeting therapies, and whether that outweighs safety risks, said Reshma Ramachandran, a Yale School of Medicine family physician and chair of the Doctors for America’s FDA Task Force.
“It’s been, in some ways, a little bit misleading to say that improvement in cognitive score has been clinically beneficial in a meaningful way,” Ramachandran said.
“Does this actually show that patients who receive this drug have an improvement in terms of their progression of Alzheimer’s disease? Will we actually be able to see something in a patient’s real life?” Ramachandran asked.
Broader Coverage Push
Sue Peschin, president and CEO of the Alliance for Aging Research, said waiting for additional evidence comes at the cost of patients living with Alzheimer’s disease.
“Neither randomized trials or patient registries are created overnight, and patients wait for access while that process is going on,” she said.
George Vradenburg, chair and co-founder of UsAgainstAlzheimer’s, agreed, saying in an interview that slowed cognitive decline can have profound impacts on the functionality of those with the memory-loss disease.
“They can go to the bathroom alone, they can be trusted to go outside without wandering, they can know how to turn the oven off and on,” he said.
But the CMS has set a precedent for future national coverage determinations for therapies targeting novel surrogate endpoints, as well as the information developers should expect to provide before distributing their therapies among broader populations, Kaltenboeck said.
Medicare’s current coverage policy “is structured to answer questions about the benefits and risks of these drugs in a broad population of patients; to what extent those benefits and risks vary by characteristics of patients and where they get their treatment; and what they look like over the long run,” she said.
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