Biogen is looking to get initial data from the FDA-mandated confirmatory trial for its Alzheimer’s disease drug Aduhelm out in four years, as the fate of this drug, and Biogen itself, rests in the balance.
Aduhelm was rejected by the FDA’s expert panel in November last year but, a few months later, was given an unexpected FDA green light through its accelerated approval pathway, which allows the agency to base approvals on surrogate endpoints, such as protein levels or tumor shrinkage, rather than a demonstrated clinical benefit, like extending patients’ lives.
It’s an option often used to get drugs for cancer and rare diseases to patients sooner, with the requirement that companies conduct a confirmatory study after approval to show their drug actually helps patients.
And this is just what Biogen is being tasked to do, with that confirmatory study, also known as a phase 4 trial, needing to show that Aduhelm can not only clear beta-amyloid—the sticky plaques that are a hallmark of Alzheimer’s—from the brain, but also that this reduction in amyloid correlates with a slowing down of cognitive decline.
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The FDA did, however, give Biogen a long timeline to get this done, nine years in fact, but today the pharma said it was hoping to get initial data out in around half that time.
The plans, detailed for the first time today, see Biogen and partner Eisai submitting the final protocol of the trial for FDA review by next March, with the first patient to be screened in the study two months later in May.
The study will swell into a global, placebo-controlled trial, aiming to enroll more than 1,300 early Alzheimer’s patients, with a primary clinical endpoint at 18 months after treatment begins.
Biogen reckons the primary completion date will be around four years after the study begins, so in 2026, well ahead of the nine years it has been given, and will also include a long-term extension to collect longer-term treatment data for up to 48 months.
“We are delivering on our commitment to accelerate the timelines with the goal to complete the confirmatory study well ahead of schedule,” said Priya Singhal, M.D., interim head of R&D at Biogen.
“Together with EMBARK, Biogen’s redosing study, and the ICARE AD study, we aim to provide data from real-world practice and clinical trials to further inform patient and physician decisions about treatment.”
Biogen will need this trial to work out: Should it not, the FDA can yank its approval for Aduhelm and deprive the pharma of a much-needed future revenue stream, coming as it hits up against some major patent losses in its multiple sclerosis franchise along with a string of flops and setbacks in the pipeline.
This also comes as Aduhelm itself is hitting up against barriers: The controversial approval from the FDA did little to help its prospects, with doctors and payers balking at its $56,000 price tag, questionable efficacy and some early safety red flags.
Despite a marketing push and Biogen being all-in on this drug, it only made $300,000 in the third quarter. How that trajectory will change is in the balance, and so much of its future will pivot on this phase 4, which will have to show genuine efficacy to appease the FDA and give doctors more confidence to prescribe it.
It also has to contend with potential new AD drugs from Roche and more notably from Eli Lilly, which is also running a head-to-head against Aduhelm for its asset donanemab. Lilly nabbed a speedy review from the FDA in October and will be quicker off the mark with a confirmatory trial, which is expected to read out in 2023, three years ahead of Biogen.