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 amyloid beta 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.

The unique binding profile of BAN2401 has been confirmed in data presented during 2019, and the results correspond well with previous studies of BAN2401. All in all, the results strengthen BioArctic’s conviction that BAN2401’s unique binding profile is important and that it differs from other amyloid beta antibodies. Professor Lars Lannfelt presented details on the binding profile at the AAIC Conference (Alzheimer’s Association International Conference®) in July 2019 and at the CTAD onference (Clinical Trials on Alzheimer’s Disease) in December 2019. BioArctic will present further data on BAN2401’s characteristics at the AAT-AD/PD conference (Advances in Alzheimer’s and Parkinson’s Therapies, AAT-AD/PD™) in April 2020 in Vienna.

In December 2019, BioArctic announced that the company had initiated a research collaboration with Eisai for deeper study of the unique binding profile of drug candidate BAN2401.

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 amyloid beta antibodies. BioArctic presented data around BAN2401’s binding profile at the Alzheimer’s Association International Conference in Los Angeles, USA, in July 2019. Please see the poster presentation below.

Eisai started the Phase 3 study (Clarity AD) in May 2019. The Phase 3 study (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, results from the study are targeted for 2022..

An open-label extension study, without placebo control, with continued BAN2401 treatment with the highest study dose for the participants in the Phase 2b study is in progress. A subset of patients from the core Phase 2b study enrolled in the open-label extension study. Eisai presented data from the extension study at the CTAD conference (Clinical Trials on Alzheimer’s Disease) in San Diego in December 2019. Measurements taken at the start of the extension study were compared with the earlier measurements taken when the core Phase 2b study was concluded. The patients in the open-label extension study went without treatment from the conclusion of the core Phase 2b study to the start of the extension phase. Data showed that amyloid reduction in the brain that occurred as a result of treatment with BAN2401 persisted after the conclusion of treatment. Differences in benefits on clinical outcomes were maintained after BAN2401 treatment in the two highest dose groups as compared with the placebo group.

During 2019 BAN2401 has been selected by the Alzheimer’s Clinical Trials Consortium (ACTC) and Eisai to be evaluated in an upcoming clinical Phase 3 program focused on prevention of Alzheimer’s disease (AHEAD 3-45). The planned clinical program will include individuals that are at risk for, or at a very early stages of, Alzheimer’s disease. The program 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 study will be starting during 2020.