BAN2401 – Alzheimer’s disease

In Alzheimer’s disease soluble, toxic amyloid beta aggregates are believed to contribute to the neurodegenerative process. BAN2401, a humanized monoclonal antibody, selectively binds to these forms of amyloid beta and eliminates them. The antibody’s unique profile is highly selective for amyloid beta oligomers/protofibrils in the brain. BioArctic’s belief is that BAN2401’s unique binding profile is important and differentiates it from other antibodies.

BAN2401 is in clinical development as the company’s first immunotherapy developed with BioArctic’s patented technology. The project is based on research from Uppsala University, Sweden. BioArctic’s partner Eisai is responsible for the clinical development of BAN2401 in Alzheimer’s disease. Eisai has started the confirmatory Phase 3 Clarity AD study with BAN2401 in early Alzheimer’s disease.

Clinical development of BAN2401 in early Alzheimer’s disease

BAN2401 Phase 2b clinical trial (NLT01767311) in early Alzheimer’s disease patients in the US, Canada, EU, Japan and South Korea has concluded. During 2018, positive and robust 18 months results of the BAN2401 Phase 2b study in 856 early Alzheimer’ disease patients were presented. Please see the press releases from July 6, July 25 and October 25 for more information. To learn more about the Phase 2b study with BAN2401, see the summary below.

This is the first study in late clinical phase that demonstrated potential disease modifying effects on both clinical function and clearance of amyloid beta in the brain. Further, the Phase 2b study also demonstrated effects on neurodegenerative biomarkers. The results strengthen BioArctic’s belief that BAN2401’s unique binding profile is important and differentiates it from other antibodies. BioArctic presented new data around BAN2401’s binding profile at the Alzheimer’s Association International Conference® 2019 (AAIC®) in Los Angeles, USA, in July 2019. Please see the poster presentation below.

For the participants in the Phase 2b study, an open-label extension study is ongoing with continued BAN2401 treatment with the highest study dose and without placebo control.

Eisai started the Phase 3 study (named Clarity AD) in May 2019. Clarity AD is a global placebo-controlled, double-blind, parallel-group, randomized study in 1,566 patients with early Alzheimer’s disease, i.e. mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s disease with confirmed amyloid pathology in the brain. Patients are allocated in a 1:1 ratio to receive either placebo or treatment. Patients are dosed twice a month with placebo or BAN2401 10 mg/kg. The primary endpoint is the change from baseline in the cognition and function scale Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment. Changes in the clinical scales AD composite score (ADCOMS) and AD Assessment Scale-Cognitive Subscale (ADAS-Cog) will be key secondary endpoints together with brain amyloid levels as measured by amyloid PET. According to Eisai, the result from the study is targeted for 2022.

BAN2401 has been selected by the Alzheimer’s Clinical Trials Consortium (ACTC) and Eisai to be evaluated in an upcoming clinical study targeting secondary prevention of Alzheimer’s disease (the A45 study). The A45 study will target the preclinical (pre-symptomatic) stage of Alzheimer’s disease. The study will enroll clinically normal participants (no/minor cognitive impairment) who have elevated levels of amyloid in the brain and are at increased risk for progression to mild cognitive impairment and Alzheimer’s disease. This study will be conducted with funding from various sources including the United States National Institute on Aging (NIA), part of the National Institutes of Health (NIH), and Eisai. According to ACTC and Eisai, the trial will be starting in early 2020.