Biogen's Aduhelm label far exceeds clinical trial population, study says. That could bring real-world surprises

While the chatter surrounding Biogen’s controversial Alzheimer's med Aduhelm has largely been centered on a pivotal Medicare reimbursement decision as of late, analysts are pointing to one new study that suggests there may be “room for surprises” when it comes to the treatment’s safety. 

In a note to clients on Wednesday, RBC Capital Markets analysts highlighted a recent study that applied Biogen’s publicly disclosed clinical trial inclusion criteria for Aduhelm to 911 patients in a geriatric outpatient unit at a hospital in Milan, Italy. 

Researchers determined that only six patients, or less than 1% of those evaluated, would have qualified for the treatment’s clinical trials—known as Emerge and Engage—ahead of the FDA’s historic approval in June, according to a letter published in the Journal of the American Geriatrics Society in late July. 

To the RBC analysts, this suggests that there’s room for previously undetected side effects for the infusion once it’s administered to thousands of patients beyond those who were represented in the clinical trials, according to the note. 

“Though real-world translation of benefits observed in clinical trials is always a concern, this small study highlights the potentially outsized limitation the tightly controlled EMERGE and ENGAGE trials might have,” RBC said.

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This could affect Aduhelm’s “narrative and ultimate launch curve, not to mention potential reimbursement breadth,” the analysts said. A Biogen spokesperson wasn’t immediately available for comment. 

Biogen is awaiting a pivotal coverage decision from the Centers for Medicare & Medicaid Services (CMS) that could determine how many patients under government-run insurance plans will have access to the treatment. Hospitals and insurers are sitting in a holding pattern until CMS decides which Alzheimer’s patients will be covered, if any. Already, the Department of Veterans Affairs has decided against covering the drug.

In the meantime, the Cambridge, Massachusetts-based drugmaker has had to navigate a maelstrom of criticism since it scored an FDA accelerated approval and priced the drug at $56,000 per patient per year.

That criticism has also trickled over to U.S. drug regulators. The FDA first granted Aduhelm a wide-ranging label that gave Biogen free rein over the nearly 6 million Alzheimer’s patients living in the U.S. Facing backlash, the agency swiftly narrowed Aduhelm’s label to people with milder forms of the disease. 

RELATED: Biogen, FDA walk back controversial Aduhelm label after weeks of fierce criticism

Still, even the FDA’s updated Aduhelm label covers far more patients than were studied under Biogen’s clinical trial program, the study’s researchers wrote.

If the new label is applied to the 911 patients examined at the Milan hospital, roughly 34% of them, or 311 people, would qualify for Aduhelm—a 52-fold increase compared to those who would qualify for a clinical trial, according to the study. 

That makes it “clear how the resulting gap between the research and ‘real world’ fields is massive,” researchers said. 

To be sure, the study has its limitations and should be cautiously interpreted, the researchers pointed out. That’s because the findings focused on the experience of just a single clinical site and were obtained by adapting the research criteria to the data routinely collected as part of the clinical activities. 

It’s also unclear whether Biogen or trial investigators made potential modifications to eligibility criteria beyond what was publicly disclosed given that there hasn’t been an article from the studies published in a peer-reviewed journal, the researchers said. 

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Meanwhile, Aduhelm is also being closely watched through post-marketing studies, including a phase 4 observational study intended to discover the drug's safety and impact on the disease in 6,000 patients, according to details released during the Alzheimer’s Association International Conference in late July. 

One gray area researchers intend to investigate is Aduhelm’s impact on diverse patients, including at least 500 African American and 500 Hispanic people. The study will also include people who may not typically qualify for clinical trials, like those with diabetes, high blood pressure and cancer, the study’s organizers told Fierce Pharma in July.