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Pink Sheet — New Model For Real World Evidence? Leqembi Registry Data Will Be Bolstered By Medicare Claims

Pink Sheet — New Model For Real World Evidence? Leqembi Registry Data Will Be Bolstered By Medicare Claims

Senior Centers for Medicare and Medicaid Services official Lee Fleisher described the game plan behind the CMS-facilitated patient registry for the new Alzheimer’s disease treatment, but former CMS official Sean Tunis is still concerned the approach won’t meet data expectations in the planned two-year window.

The Centers for Medicare and Medicaid Services will link Medicare claims data on Alzheimer’s to supplement the data from its bare-bones registry on Eisai Co., Ltd. and Biogen, Inc.’s Leqembi, a new treatment for the disease.

CMS announced specifics on its patient registry after the US Food and Drug Administration’s traditional approval of Leqembi on 6 July.  (Also see “Broader Medicare Coverage For Leqembi Begins As CMS-Backed Registry Opens For Business” – Pink Sheet, 6 Jul, 2023.) The registry requires entry of relatively few details on patients prescribed the drug over two years and was designed as an easy way to satisfy Medicare coverage with evidence development (CED) requirements.

CMS Clinical Standards and Quality chief medical officer Lee Fleisher discussed the agency’s thinking about the registry and how it satisfies the CED policy during an 11 July public meeting sponsored by Friends of Cancer Research.

“We’re very excited about what we did in this registry. I would call it real world evidence,” he began. “The question became, can we actually merge [Medicare] claims data” with the CMS registry data and therefore not mandate collection of data on demographics or “disease states” in the registry because “that’s all in our claims.”

The combination would allow the agency to require only “very parsimonious” data in the registry that would take just “four and a half minutes” for clinicians to enter. But “the scientific community can use that enhanced data – or our colleagues at FDA – to really see … what I would consider the future of real-world evidence,” Fleisher said.

Leqembi developers and patient groups welcomed details about the CMS-facilitated registry amid concerns that a more rigorous approach involving complicated and extensive data entry would impede access to treatment.

Answers To The CED Questions Unlikely In Two Years

However, some policy experts are concerned that the approach will not produce the evidence CMS says it needs. When the agency announced the CED requirements for amyloid-targeting monoclonal antibodies for Alzheimer’s disease like Leqembi, it said that in order to consider the drugs “reasonable and necessary” and eligible for Medicare coverage, three questions must be answered:

  • Can the treatment’s clinical benefit be replicated in the general Medicare population,

  • Do certain subgroups experience different benefits and harms, and

  • How do those benefits and harms change over time.

“My overall view [on the registry plan] is it’s a really good effort given the constraints that CMS was under, particularly the strong advocacy in favor of unrestricted coverage,” Sean Tunis, former CMS chief medical officer and now a principal at the consulting firm Rubix Health, told the Pink Sheet.

CMS “did a really good job of designing a data collection approach that is very little burden in terms of how long it would take to collect the important data elements,” he said. “And there is some chance that they’ll get some useful information.”

However, “if the hope is to end CED in two years once this CMS study is done, it seems like the potential limitations in the design and the approach will mean that in two years we won’t have answers to these questions and then CMS is going to be in a tough spot,” Tunis added.

He suggested a better approach may have been for CMS to bring together patient groups, industry, academics, the FDA and the National Institutes of Health before the original CED policy was issued to “figure out collectively what is the least burdensome way we can answer these questions” and “make sure we have the means and the resources to do it.”

Leqembi Postmarket Studies Could Supplement CMS Data

Fleisher suggested that the postmarket safety data that the FDA required Eisai to collect could also be useful to Medicare. The FDA mandated three studies, including a registry-based study.  (Also see “Leqembi Safety Is Focus Of Three Postmarketing Requirements From US FDA” – Pink Sheet, 10 Jul, 2023.)

“You can have multiple registries to meet our CED criteria,” Fleisher said. “And the goal will be that if FDA, for any postmarketing study that is approved, that the study also gets submitted to CMS.”

However, “it is … worth noting that the timeline for these [FDA-required] studies does not envision generating any results for several years,” Tunis said. “The first interim report for the first study is scheduled for October 2025. The CMS portal aims to have answered all three CED questions by July 2025 … which seems unrealistic.”

As to whether the FDA’s concerns could be answered by the data generated by CMS, FDA Center for Drug Evaluation and Research director Patrizia Cavazzoni said during the FOCR meeting that the agency “asked for a registry as a postmarket requirement … because it recognizes that there is a lot of information that is not necessarily collected in clinical practice, or may not be billed for, which is really what claims are for.”

“It really comes down to the question and the data and whether the data are fit for purpose for the questions that we want to have answered, and it’s really on a case-by-case basis,” she said. The FDA suggested in the Leqembi approval letter that the patient registry sponsored by the Alzheimer’s Association, called ALZ-NET, could collect the needed information, but did not mention using the CMS-facilitated registry.