Seven months after disclosing disappointing initial results from a Phase II trial of BAN2401, Biogen and Eisai this week released a more positive topline “final analysis” showing that their Alzheimer’s disease candidate achieved a statistically significant slowing of clinical decline and reduction of amyloid beta accumulated in the brain.
The Phase II trial, Study 201 (NCT01767311), achieved statistically significance on two key endpoints, the companies said.
One was a slowdown of progression in Alzheimer’s Disease Composite Score (ADCOMS) following 18 months of treatment in patients receiving the highest treatment dose (10 mg/kg biweekly), compared to placebo. That dose began to show statistically significant clinical benefit as measured by ADCOMS as early as 6 months, including at 12 months, Biogen and Eisai said.
The other endpoint was a reduction of amyloid accumulated in the brain measured via amyloid-positron emission tomography (PET). Results of amyloid PET analyses at 18 months were also statistically significant at the highest dose, according to Eisai and Biogen—including reduction in amyloid PET standardized uptake value ratio (SUVR) and amyloid PET image visual read of subjects converting from positive to negative for amyloid in the brain.
Shares of Biogen this afternoon jumped 19% from yesterday’s close to $298.81—to $356.09 as of 3:06 p.m.
“We believe these results offer patients some hope as they lift the sentiment around the potential to find a treatment for slowing disease progression in Alzheimer's (in which no product has worked so far), and more specifically around the anti-amyloid approach toward Alzheimer’s disease, which has seen several failed attempts in the past,” Canaccord Genuity biotechnology analyst Sumant Kulkarni said.
“Very Encouraging Results”
Study 201 is a placebo-controlled, double-blind, parallel-group, randomized study in 856 patients with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's dementia—collectively known as early Alzheimer’s disease—with confirmed amyloid pathology in the brain.
Detailed results will be presented at unspecified future academic conferences, the companies stated.
“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, M.D., chief clinical officer and CMO, Neurology Business Group, Eisai. “We will discuss these very encouraging results with regulatory authorities to determine the best path forward.”
Added Alfred Sandrock, M.D., Ph.D., Biogen executive vice president and CMO: “These BAN2401 18-month data offer important insights in the investigation of potential treatment options for patients with Alzheimer’s disease and underscores that neurodegenerative diseases may not be as intractable as they once seemed.”
Back in December, Biogen and Eisai acknowledged that they had not achieved the early signals of efficacy they sought through a Bayesian analysis at 12 months. That analysis benchmarked success as an 80% or higher probability of achieving a Clinically Significant Difference of a 25% or greater reduction in the rate of decline in ADCOMS compared to placebo. The study design included 16 interim analyses that assessed potential for futility or stopping for safety. Neither of these conditions was met.
Biogen and Eisai hope to succeed where numerous other drug developers have failed in the long struggle to create successful new drugs for Alzheimer’s disease. Only a handful of drug successes have ever reached the market, and even they have merely slowed progression of symptoms by 6 to 12 months.
A 2014 Cleveland Clinic study found a 99.6% failure rate of clinical trials for Alzheimer's disease drug candidates between 2002 and 2012. That study found high attrition rates for Alzheimer’s disease treatments, with 72% of agents failing in Phase I, 92% failing in Phase II, and 98% failing in Phase III.