As Centers for Medicare and Medicaid Services (CMS) prepares to announce the final coverage decision for a revolutionary new Alzheimer’s drug, a paper from Biogen and the National Minority Quality Forum (NMQF) highlights the important role of real-world evidence in Alzheimer’s R&D.
The first disease-modifying treatment for Alzheimer’s
In June 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval for Aduhelm—the first disease-modifying treatment for Alzheimer’s, and the first new treatment for the disease in 20 years.
“Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s,” said Patrizia Cavazzoni, M.D., Director of the FDA’s Center for Drug Evaluation and Research. “As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
Developed by Biogen, a member of the Biotechnology Innovation Organization (BIO), the treatment “consistently and very convincingly” reduced plaques believed to contribute to the disease, according to FDA.
“The approval of Aduhelm represents a crucial inflection point in our collective battle against Alzheimer’s disease. By addressing a defining pathology of the disease, this novel therapy has the potential to help fundamentally change the way patients are diagnosed and treated,” said Biogen CEO Michel Vounatsos.
‘A dangerous and far-reaching precedent’
In early 2022, CMS released a National Coverage Determination (NCD) for Aduhelm, proposing to restrict coverage to patients participating in clinical trials.
“The announcement by CMS sets a dangerous and far-reaching precedent for patients struggling with Alzheimer’s and other difficult to treat diseases,” said BIO President and CEO Dr. Michelle McMurry-Heath.
“Limiting coverage only to patients enrolled in government-mandated randomized clinical trials means that most of those suffering from Alzheimer’s would be denied access to an approved medicine simply because of where they live or where they go for care,” she continued. “The CMS proposal also would require post-approval randomized controlled trials for all future drugs in this class, regardless of the type and volume of evidence demonstrated during FDA-required trials and regardless of whether future drugs are approved during an accelerated pathway or through traditional channels.”
Why real-world evidence matters
As required by FDA, Biogen will conduct a post-marketing confirmatory trial. The “global, placebo-controlled trial” will enroll 1,500 patients with early Alzheimer’s and “confirmation of amyloid beta pathology.” The first patient will enter screening in May 2022, with the trial’s completion expected in four years, Biogen announced in March.
However, in addition to clinical trial data, it’s also important to collect real-world evidence (RWE), which will allow inclusion of “larger patient populations that are historically underrepresented in randomized controlled trials, including, for example, patients who are ethnically/racially/
“Alzheimer’s disease trials historically have struggled to enroll participants from the Black/African-American community – overall, trials have had an average of 2-3% representation,” according to a recent paper from Biogen and National Minority Quality Forum (NMQF), a research and educational organization in Washington D.C.
Biogen partnered with NMQF to improve the diversity of trials as well as pursue “complementary RWE efforts that may open up these data collection efforts to a broader population,” per Biogen Chief Medical Officer Dr. Maha Radhakrishnan.
Biogen aims to enroll 18% of U.S. trial participants from Black/African American and Latino communities, and to collect real-world data including “claims and billing activities, product and disease registries, and patient-generated data including those captured in home-use settings.”
However: Biogen won’t be able to get that data if the drug’s only covered for patients participating in clinical trials.
“Most Medicare beneficiaries that meet FDA-approval criteria would not be able to access the drug under this proposal. There also is the issue that many enrolled in randomized trials won’t even have access to the drug, since they will be receiving the placebo. In addition, under this proposal, coverage wouldn’t even begin to be available until a trial is approved and enrolling patients, likely a year or more after any coverage decision is final,” said BIO’s Dr. McMurry-Heath in January.
CMS intends to announce its final decision by Monday.