The latest data from a Phase 2 trial (study 201) demonstrates that BAN2401 can slow cognitive decline, providing additional evidence of its potential as a disease-modifying therapy for Alzheimer’s disease, according to Eisai and Biogen, which are jointly developing the investigative therapy.
BAN2401 is an engineered antibody designed to specifically bind and neutralize toxic amyloid aggregates, which are well-known contributors of the neurodegenerative process in Alzheimer’s disease.
The Phase 2 (study 201) trial (NCT01767311) enrolled 856 patients with early Alzheimer’s disease who had amyloid protein accumulation in the brain.
Participants were randomly assigned to receive one of five treatment regimens with the investigative antibody — 2.5 mg, 5 mg, or 10 mg per kg body weight once every two weeks; 5 or 10 mg per kg body weight once a month; or a placebo.
The results, announced by Eisai and Biogen, revealed that patients treated with the 10 mg/kg every two weeks regimen for 18 months — the highest tested dose of BAN2401 — had a 30% slower cognitive decline compared to placebo-treated patients.
This positive effect, determined by the Alzheimer’s Disease Composite Score (ADCOMS), was first noted as early as six months into treatment.
Evaluation with the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) and the Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB) also revealed slower clinical decline by 47% and 26%, respectively, in these patients at 18 months.
This last result was even better than researchers expected, surpassing initial expectations, which were hoping for a prespecified difference between groups of 25%.
During the study, the rate of decline in the placebo group was consistent with other clinical data previously reported by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in the United States.
Taken together, these data demonstrated that treatment with the highest tested dose of BAN2401 had a 98% greater chance of preventing clinical decline than placebo.
In addition to these positive results, researchers reported that the levels of amyloid proteins were significantly reduced in the brain after BAN2401 treatment, in a dose-dependent manner.
Patients treated with 10 mg/kg BAN2401 every two weeks experienced reduced amyloid proteins from a mean value of 74.5 at the start of the study to 5.5 at 18 months into the trial, as determined by brain imaging analysis with positron emission tomography (PET) scans.
About 81% of these patients changed from amyloid positive to amyloid negative by the end of the trial.
Overall, BAN2401 had an acceptable safety profile through the 18-month study.
These new results were discussed at the Alzheimer’s Association International Conference (AAIC) 2018 held July 22-26 in Chicago.
The oral presentation was titled “Treatment of Early AD Subjects with BAN2401, an Anti-Aβ Protofibril Monoclonal Antibody, Significantly Clears Amyloid Plaque and Reduces Clinical Decline.”
This top-line data comes on the heels of an announcement in December 2017 that the therapy candidate had failed to promote significant changes after 12 months. Based on these initial disappointing results, an independent review committee declared the data was inconclusive, and researchers extended the trial for an additional six months.
Earlier this month, Eisai and Biogen announced that treatment with the investigative drug over 18 months could reduce the accumulation of amyloid fibers in the brain.