Biogen plans to power up an FDA-mandated postmarketing study of Alzheimer’s disease drug Aduhelm—a trial that could be the main revenue source for the controversial medicine for years to come if a Medicare coverage policy is finalized.
The Aduhelm confirmatory trial, dubbed ENVISION, will enroll 1,500 early Alzheimer’s patients instead of the previously announced 1,300, Biogen said. The planned increase is meant to “further strengthen the data the study will provide,” the company added.
Results from the trial will be set up to inform about Aduhelm’s clinical benefit and possibly convert an FDA accelerated approval, which was based on biomarker data, into a full one. But the trial could carry more meaning to Biogen.
In a recent draft ruling, the Centers for Medicare & Medicaid Services (CMS) said it would restrict Medicare coverage for anti-beta-amyloid drugs like Aduhelm to patients who participate in a clinical trial. As currently the only marketed anti-amyloid antibody for Alzheimer’s, Aduhelm could see very limited commercial use under the rule, or, as RBC Capital Markets analyst Brian Abrahams put it, the proposed move “could effectively spell the end for Aduhelm.”
As part of the tentative decision, CMS is requiring that a clinical trial must reflect the diversity of the national population of Alzheimer’s. Among all the efficacy and safety questions around Aduhelm, inadequate representation of people of different racial and ethnic backgrounds in its phase 3 program has previously also raised eyebrows.
For ENVISION, Biogen said it aims to enroll 18% of U.S. participants from Black and Latinx populations. But the very definition of proper racial representation is up to debate. As evidence of the lack of racial understanding in Alzheimer’s research, a report (PDF) by the Alzheimer’s Association found that the prevalence of the neurodegenerative disease in older Black Americans could be anywhere from 14% to 100% higher than their white counterparts.
The 18% goal “matches the diversity among Americans diagnosed with early Alzheimer’s disease, while at the same time, the trial will generate substantial data to verify the effectiveness of Aduhelm,” Priya Singhal M.D., Biogen’s interim head of R&D, said in a statement.
RELATED: For Biogen's Aduhelm, narrow coverage from CMS 'could effectively spell the end': analyst
The ENVISION study will measure patients’ cognitive decline on the Clinical Dementia Rating-Sum of Boxes at 18 months as its main goal, same as the design for Aduhelm’s two phase 3 trials. Biogen said it expects to complete the trial about four years after the study begins, which is now planned for May 2022.
That means, if ENVISION became the only trial that CMS eventually signs off on, then Aduhelm would only reach roughly a thousand patients for four years, considering some participants will be assigned to receive placebo in the control group. By contrast, Biogen had previously estimated about 50,000 patient initiations this year if Medicare reimbursement were in place.
Besides ENVISION, Biogen and partner Eisai have an observational phase 4 study dubbed ICARE AD-US, which is designed to evaluate Aduhelm in real-world clinical practice. The study aims to enroll altogether 6,000 patients. But it’s not a randomized controlled trial that CMS is looking for. In addition, a phase 3b study coded EMBARK has rolled over participants in past Aduhelm studies to understand the effects of redosing the drug over the long term. That study is not recruiting new patients.
RELATED: Biogen CEO Vounatsos summons support to fight Aduhelm's paralyzing coverage decision
Biogen is contesting the CMS proposal before a final decision in April, and it has encouraged supporters—including several Alzheimer’s patients groups—to do the same. The requirement of a clinical trial would limit access to a few medical centers, creating a health equity problem, Biogen has argued. The company is calling for coverage with restrictions that aligns with the criteria used in the drug’s phase 3 trials.
A final CMS policy could have “greater leeway on site selection, blinding and enrollment numbers,” RBC’s Abrahams said in a note last week after speaking with a CMS expert. But enrollment in a clinical trial will still likely be required for Aduhelm reimbursement, which will lead to a “substantially compressed potential launch trajectory,” he said.
For the Aduhelm studies, Biogen will “implement multiple strategies to help overcome barriers to diverse patient enrollment,” the company said. Access to medical centers, knowledge of the drug’s benefit-risk profile and financial or logistical burdens were cited among the hurdles.
Biogen currently has the amyloid Alzheimer's market to itself, but that could soon change, adding yet more pressure to the pharma. That pressure comes in the form of Eli Lilly, which recently submitted its rival drug, donanemab, for an accelerated approval in Alzheimer's, and expects to complete its rolling submission by the end of the first quarter.
If all goes to plan at the FDA, the company aims to launch donanemab toward the end of the year and could be making $6 billion in sales by 2026, according to figures from Evaluate.
It’s also slated to have a confirmatory trial by 2023, three years ahead of Biogen. And that's not all: By the middle of next year, Lilly also expects to have data from a head-to-head trial pitting its drug against Aduhelm. If that marks a clear win for the pharma, Biogen may be in for more market pain.
Editor's Note: The story has been updated with additional information and comments on the new ENVISION trial diversity commitments.