Positive Topline Results Announced for BAN2401 in Phase II Alzheimer Trial

July 6, 2018

The anti-amyloid protofibril antibody achieved statistical significance in its key efficacy endpoints after 18 months.

Lynn Kramer, MD

Eisai and Biogen have announced that BAN2401, the duo’s investigational humanized monoclonal antibody, has shown positive topline results from a phase II study in patients with Alzheimer disease (AD).1

The anti-amyloid protofibril antibody achieved statistical significance in its key efficacy endpoints after 18 months, resulting in a slowed progression in AD Composite Score (ADCOMS), as well as a reduction of amyloid accumulation in the brain, as measured by amyloid-positron emission tomography (PET).

“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, MD, the chief clinical and medical officer in the Neurology Business Group at Eisai, in a statement.2 “We will discuss these very encouraging results with regulatory authorities to determine the best path forward. We continue to work towards the goal of delivering BAN2401 to patients and healthcare professionals as early as possible.”

According to Biogen and Eisai, the detailed findings will be presented at future academic conferences—including the Alzheimer Association International Conference (AAIC), in Chicago, Illinois later this month.

The double-blind, placebo-controlled, parallel-group trial randomized 856 patients with mild cognitive impairment (MCI) caused by either AD or mild Alzheimer dementia, to either placebo, or 1 of 5 active treatment arms, consisting of 3 biweekly doses (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) and 2 monthly doses (5 mg/kg or 10 mg/kg).

Results showed that the highest dose, 10 mg/kg administered biweekly, resulted in a slowing of disease progression after 18 months compared to placebo. In that group, the amyloid PET analysis also showed significant reductions of 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.

Safety results showed that the therapy was acceptably tolerable. The most common treatment-emergent adverse event (AE) reported was infusion-related reactions, most being mild to moderate, and Amyloid-Related Imaging Abnormalities (ARIA). ARIA edema did not occur in >10% of patients in any treatment arms, nor <15% of patients with APIOE4 at the highest dose, per protocol safety and reporting methods.

Jeff Cummings, MD, the founding director of Cleveland Clinic Lou Ruvo Center for Brain Health, noted in a statement that he found the results "impressive" and that he was looking "forward to seeing the full data set shared with the broader Alzheimer’s community as we advance against this devastating disease.”

The therapy selectively binds to neutralize and eliminate the soluble, toxic Aβ aggregates which are believed to aid the neurodegenerative process in AD. As such, BAN2401 may have the potential to have a pathological effect on the disease to slow down its progression.

The announcement of positive results marks a turnaround for BAN2401, which, prior to the 18-month assessment, had not proven as successful as hoped. In December 2017, Eisai and Biogen announced that Study 201’s primary outcome—a ≥80% probability of achieving a clinically significant difference, or a ≥25% reduction in the rate of decline in ADCOMS compared to placebo—was not met.3 Despite this, the manufacturing pair noted that the primary outcome was developed to enable a quicker entry to phase III development for the therapy, based on Bayesian analysis at the 12-month point.

This, according to those like Gregory Day, MD, MSc, is welcoming. Day, at the American Academy of Neurology’s (AAN) Annual Meeting in April, told NeurologyLive ’s sister publication MD Mag that due to a lack of success in trials acquiring funding for trials in AD has become a challenge.

“You don’t have to look too far to see the graveyard of past studies that have not panned out and the billions of dollars that have been spent pursuing therapies that were not effective,” Day said. “What do we need to change that landscape? One drug that’s effective will certainly change that landscape, as it has for other disease states, like multiple sclerosis.”

“The prospect of being able to offer meaningful disease-modifying therapies to individuals suffering from this terrible disease is both exciting and humbling,” said Alfred Sandrock, MD, PhD, the executive vice president and chief medical officer at Biogen, in a statement. “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.”

REFERENCES:

1. A study to evaluate

safety

, tolerability, and efficacy of BAN2401 in subjects with early Alzheimer's disease. National Institutes of Health Clinical Trials website. clinicaltrials.gov/ct2/show/NCT01767311. Published January 14, 2013. Accessed July 6, 2018.

2. Eisai and Biogen announce positive topline results of the final analysis for BAN2401 at 18 months [press release].

Esiai

Public Relations Department. Tokyo, Japan. Biogen Inc. Public

Affiars

. Cambridge, Massachusetts. investors.biogen.com/news-releases/news-release-details/eisai-and-biogen-announce-positive-topline-results-final. Accessed July 6, 2018.

3. Adaptive phase II study of BAN2401 in early Alzheimer disease continues toward 18-month endpoint [press release].

Esiai

Public Relations Department. Tokyo, Japan. Biogen Inc. Public

Affiars

. Cambridge, Massachusetts. investors.biogen.com/news-releases/news-release-details/adaptive-phase-ii-study-ban2401-early-alzheimers-disease. Accessed July 6, 2018.