A phase 2 Alzheimer’s trial—once nearly consigned to the heap of disappointing attempts against the disease—has re-emerged with new positive results, showing that an anti-amyloid beta protofibril antibody can slow clinical symptom decline, as well as reduce the accumulation of plaque in the brain.
Biogen and Eisai’s BAN2401 did not present promising results last December, with 12-month data failing to clear the bar compared to placebo. The companies had hoped their adaptive trial design, employing Bayesian statistics, would provide a faster and cheaper route to phase 3 development compared to traditional protocols.
But they stuck with it, keeping the trial blinded and seeing it through 18 months of follow-up in 856 patients with early disease. Using the highest dose, as well as more conventional statistical methods, the companies saw statistically significant slowing of the course of Alzheimer’s symptoms, as measured by a combination of cognitive assessments and dementia ratings.
In addition, PET scans of the brain measuring amyloid plaque buildup showed more patients moving from the positive column to the negative column. When looking at the entirety of the data, the highest treatment dose of BAN2401 began to show statistically significant clinical benefit as early as six months into therapy, as well as at the 12-month hurdle.
While the companies plan to present the full results at a conference in the future, the topline numbers alone are not just good news for the drug and its sponsors, but also for the very idea of using amyloid beta as a therapeutic target.
“This is the first late-stage anti-amyloid antibody study to successfully achieve statistically significant results at 18 months, further validating the amyloid hypothesis,” said Lynn Kramer, chief clinical officer and chief medical officer of Eisai’s neurology unit. “We will discuss these very encouraging results with regulatory authorities to determine the best path forward.”
BAN2401 also demonstrated acceptable tolerability through 18 months, the companies said. Incidence of amyloid-related edema did not top 10% at any dose, with rates under 15% in patients with APOE4 taking the highest dose.
“The prospect of being able to offer meaningful disease-modifying therapies to individuals suffering from this terrible disease is both exciting and humbling,” said Biogen’s chief medical officer, Alfred Sandrock Jr.
“These BAN2401 18-month data offer important insights in the investigation of potential treatment options for patients with Alzheimer’s disease and underscore that neurodegenerative diseases may not be as intractable as they once seemed,” he added.
The news is welcome following the collapse of several late-phase Alzheimer’s programs over the past few years—especially with other amyloid-targeting drugs, such as BACE inhibitors—whether due to a lack of efficacy or drug safety issues.
Earlier this year, Janssen halted a phase 2b/3 trial of its BACE inhibitor atabacestat in preclinical Alzheimer’s disease, after liver toxicity made it impossible to continue—a result piled on top of past attempts from Eli Lilly, Roche, Merck and others.
And last month, phase 2 data from Eisai and Biogen’s own oral BACE inhibitor, elenbecestat, demonstrated reductions in amyloid beta levels in 35 patients, but it did not slow symptom decline more than placebo.
And in February, Biogen tweaked its phase 3 trial of another antibody program, aducanumab—adding 510 patients after seeing more variability than expected in a blinded sample size re-estimation—causing its shares to take a 9% tumble. But with the latest study readout, Biogen’s stock was up 13% in premarket trading, with Eisai seeing a 19% gain.