Biogen and Eisai release positive 18-month data from Alzheimer's study

The US-based firm and its Japanese partner said the study achieved statistical significance on key predefined endpoints, evaluating efficacy at 18 months on slowing progression in Alzheimer's Disease Composite Score (ADCOMS), and on a reduction of amyloid accumulated in the brain as measured using amyloid-PET (positron emission tomography).

It described Study 201 as a placebo-controlled, double-blind, parallel-group, randomised study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild Alzheimer's dementia, collectively known as early Alzheimer's disease, with confirmed amyloid pathology in the brain.

Efficacy was evaluated at 18 months by predefined conventional statistics on ADCOMS, which combined items from the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale and the Mini-Mental State Examination (MMSE), to enable sensitive detection of changes in early AD symptoms.

Patients were randomised to five dose regimens - 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly and 10 mg/kg biweekly, or placebo.

The two companies said topline results of the final analysis of the study demonstrated a “statistically significant” slowing of disease progression on the key clinical endpoint (ADCOMS) after 18 months of treatment in patients receiving the highest treatment dose - 10 mg/kg biweekly - as compared to placebo.

Results of amyloid PET analyses at 18 months, including reduction in amyloid PET standardised uptake value ratio (SUVR) and amyloid PET image visual read of subjects converting from positive to negative for amyloid in the brain, were also said to be statistically significant at that dose.

Dose-dependent changes from baseline were observed across the PET results, the board reported, as well as the clinical endpoints.

Further, the companies said the highest treatment dose of BAN2401 began to show statistically significant clinical benefit as measured by ADCOMS as early as six months, including at 12 months.

Biogen and Eisai said BAN2401 demonstrated an acceptable tolerability profile through 18 months of study drug administration.

The most common treatment emergent adverse events were infusion-related reactions and Amyloid Related Imaging Abnormalities (ARIA).

Infusion related reactions were described as mostly mild to moderate in severity.

Incidence of ARIA-E (edema) was reported as occurring in no more than 10% in any of the treatment arms, and less than 15% in patients with APOE4 at the highest dose per the study protocol safety and reporting procedures.

“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, executive vice president and chief medical officer at Biogen.

“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.”

As the companies reported in December, the study did not achieve its primary outcome measure, which was designed to enable a potentially more rapid entry into Phase III development based on Bayesian analysis at 12 months of treatment.

Upon the final analysis at 18 months using predefined conventional statistical method, the study did demonstrate a statistically significant slowing of disease progression on the key clinical endpoint (ADCOMS) after 12 months of treatment in patients receiving the highest treatment dose (10 mg/kg biweekly) as compared to placebo.

Biogen and Eisai noted that the release discussed investigational uses of an agent in development, and was not intended to convey conclusions about efficacy or safety.

“There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval,” the joint statement read.