Phase 2 Study of BAN2401 Fails to Meet 12-month Goal; Proceeds to 18-month Analysis
BAN2401, an investigational anti-amyloid beta antibody therapy for Alzheimer’s disease, has failed to reach the primary endpoint of a Phase 2 clinical trial measured after 12 months of therapy.
Study 201 will continue following the predefined protocol, where a comprehensive analysis will be performed after an 18-month treatment period. Final results are expected in the second half of 2018.
The Phase 2 trial (NCT01767311) enrolled patients with early Alzheimer’s disease carrying biomarkers of brain amyloid pathology, i.e., with build-up of beta-amyloid plaques as shown by positron emission tomography (PET) or by analyzing patients’ cerebrospinal fluid (CSF). Patients were from two two clinical subgroups — those with Alzheimer’s disease-induced mild cognitive impairment, or those with mild Alzheimer’s Disease dementia.
Patients were assigned randomly to a placebo, control group or to one of five BAN2401-treatment groups: three of them testing escalating dose groups of BAN2401 – 2.5, 5, and 10 mg/kg taken once every two weeks), or to two-dose groups (5 and 10 mg/kg) given monthly. BAN2401 is administered intravenously.
The trial included 16 interim analyses, introduced as a means to assess safety issues. But during the 12-month period none were detected, ensuring the trial’s safety to continue up to 18 months.
Researchers determined the effectiveness of BAN2401 by measuring the changes in the Alzheimer’s Disease Composite Score (ADCOMS), a new endpoint developed by Eisai, after 12 months of treatment. Specifically, the therapy’s success was defined as an 80 percent or higher chance for patients to reach at least a 25 percent decrease in the rate of decline in ADCOMS compared to placebo.
After 12 months of treatment, however, researchers observed no significant change from baseline in the ADCOMS.
“We now await the final study analysis which will be conducted after 18 months of treatment, which represents an amount of treatment time that is considered as appropriate for assessing efficacy in disease modifying agents for Alzheimer’s disease,” said Lynn Kramer, MD, in a press release. Kramer is chief clinical officer and chief medical officer, Neurology Business Group, Eisai.
In the final analysis, researchers again will assess the changes from baseline in ADCOMS, but also in the Clinical Dementia Rating Sum of Boxes (CDR-SB). Additional parameters for evaluating the therapy’s effectiveness will include measuring beta-amyloid deposition by PET and the volume of a brain region called hippocampus, as a way to assess progression of Alzheimer’s disease.