Medicare Coverage-In-Clinical-Trials Policy For Alzheimer’s Drugs Could Stifle Access For Years

GAP President John Dwyer spoke to Pink Sheet about the CMS NCD proposal.

The Centers for Medicare and Medicaid Service’s proposal to allow Medicare to pay for amyloid-directed monoclonal antibody drugs for Alzheimer’s only when they are used in randomized controlled clinical trials could significantly curtail access to the drugs for at least four years, according to John Dwyer, president of the Global Alzheimer’s Platform Foundation and co-founder of UsAgainstAlzheimer’s.

Dwyer discussed the practical challenges posed by the coverage with evidence development requirement in the Medicare draft national coverage determination in an interview with the Pink Sheet. The Global Alzheimer’s Platform Foundation works on speeding the delivery of innovative Alzheimer’s disease therapies by enhancing the efficiency of clinical trials. Funding for the work comes from philanthropies and pharmaceutical firms.

The NCD, if finalized in its current form, would restrict access to Biogen, Inc. and Eisai Co., Ltd.’s currently marketed Aduhelm (aducanumab) and drugs in development from Eli Lilly and Company (donanemab), Eisai (lecanemab) and Roche Holding AG (gantenerumab). It was released on 11 January.

CMS has emphasized that it welcomes public comments on the draft, which suggests the agency might change its
mind about the requirement.

“My estimate is this is going to add a minimum of four, maybe up to six or seven years’ delay for any volume of patients to get on this therapy or any of its sister therapies if they go through with this,” Dwyer said.

“In my professional experience you will not get the first CMS study as described in this proposal even started until the fourth quarter of 2023,” he pointed out. “Basically, it takes two years to start one and then, who knows how many years we’ll need to enroll and track what constitutes clinical benefit to satisfy Medicare,” which “is not clearly stated [in the NCD] and that is not a trivial question.” He also noted CMS emphasizes it wants data showing the safety and efficacy of the drugs in the Medicare population, including African Americans and Latinos who are underrepresented in clinical trials. But that is notoriously difficult to achieve and will slow enrollment and completion of studies even further, Dwyer maintained.

CMS’s proposed requirement that trials be conducted in hospital outpatient centers presents further challenges
because “major hospital systems have not traditionally been fast or successful at recruiting underrepresented
populations, even though some are nestled in African American or Latino communities,” he said. CMS has said, “’We want to ensure equity and access here,’ but the math doesn’t work, and the locations don’t work.” Furthermore, whether enrollees would be responsible for a copay on treatment “is yet to be determined.”

It is unclear whether clinical trials being planned by Biogen and Lilly would meet CMS’s standards for qualifying studies under the NCD, Dwyer noted. Biogen is gearing up for a confirmatory randomized controlled trial that it is required to conduct under Aduhelm’s accelerated approval.

The company plans to begin patient screening for the study in May, with a primary completion date of approximately four years after the study begins – almost twice as fast as the original timeline specified by the FDA.

Lilly is planning a Phase III head-to-head study of donanemab versus Aduhelm for plaque clearance, which could have data in the second half of 2022. The company is also seeking an accelerated approval for donanemab from the US Food and Drug Administration.

Instead of moving ahead with the coverage with evidence development requirement, “I strongly believe [CMS] needs to clear off the RCT structure” at least until “they get another study out of the field, like the Lilly head-to- head maybe,” Dwyer said. “But what I really think is give the drug coverage but be very prescriptive on the conditions for prescribing,” including “rigorous MRIs” to detect or address amyloid-related imaging abnormalities (ARIA) if it occurs, he emphasized. Unless it is modified, “I’m reading [the draft NCD] as saying any drug coming out of FDA with accelerated approval irrespective of their data … goes through this process,” Dwyer said. “For industry, why would you go through the trouble of conducting an RCT” on a drug candidate “and spend hundreds of millions, if not $1bn on it, for the luxury and privilege of doing it all over again for CMS?”

Originally posted by Pink Sheet on January 17, 2022.

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