Latest results from the long-term extension of a Phase 1b study assessing increasing and fixed doses of aducanumab continue to show its potential as a therapy for early or mild Alzheimer’s disease.
Similar to previous interim analyses, data collected for up to 48 months reveal that the investigative treatment can effectively reduce the burden of amyloid plaques — a hallmark of the disease – and prevent cognitive decline in Alzheimer’s patients.
Aducanumab, formerly known as BIIB037, is a monoclonal antibody being developed by Biogen in collaboration with Eisai. Prior preclinical and clinical data suggest that aducanumab’s therapeutic potential resides in its ability to target disease-causing amyloid protein clusters.
The ongoing PRIME trial (NCT01677572) is evaluating the safety, tolerability, and overall reactivity of aducanumab in patients with prodromal (early) or mild Alzheimer’s disease dementia.
A total of 196 participants, ages 50 to 90, were enrolled across some 30 research centers in the United States. They were randomized to receive either a fixed dose of aducanumab or placebo — 1, 3, 6, or 10 mg/kg — or to undergo a titration regimen in which they received a gradually increasing dose of the antibody or placebo up to a maximum of 10 mg per kilogram of body weight.
From the initial group of 196 patients, 143 entered the long-term extension study. In this second part of the trial, patients were allocated across six dosing arms: placebo patients switching to treatment; 1 mg/kg aducanumab patients moving to 3 mg/kg doses; fixed doses of 3 mg/kg, 6 mg/kg, and 10 mg/kg; and different dose concentrations (titration group).
The latest analyses include data from the placebo-controlled period, and extension study patients treated with aducanumab up to 36 months in the titration arm and up to 48 months in fixed-dose groups.
Collectively, amyloid plaque levels as determined by positron emission tomography (PET) continued to decrease in a dose- and time-dependent manner in both titration and fixed-dose patients given aducanumab continuously.
Similar to prior data, patients treated with the highest fixed-dose of the antibody continued to show amyloid plaque at levels below to what is considered a positive scan for Alzheimer’s.
Data collected using the Clinical Dementia Rating sum of boxes (CDR-SB) and the Mini-Mental State Examination (MMSE) also suggest a treatment-associated benefit in preventing cognitive decline over 36 and 48 months.
“The results are generally consistent with previous interim analyses, and there were no changes to the risk-benefit profile of aducanumab,” a Biogen spokesperson stated in a press release.
Of the 185 patients treated with aducanumab in the PRIME trial, 46 patients experienced amyloid imaging abnormalities (ARIA), typically toward the beginning of treatment. ARIA are abnormal differences seen in neuroimaging of Alzheimer’s patients, associated with amyloid-modifying therapies such as aducanumab.
These event were typically without clinical symptoms, resolving or stabilizing within four to 12 weeks.
In the extension part of this study, the most frequent adverse events reported were headaches, falls, and ARIA.
The companies are planning to share more detailed extension study results at an upcoming scientific meeting.