Phase 3 trial results also indicate that Alzheimer disease clinical decline was reduced in participants who had plasma p-tau181 reduction at 78 weeks.
Biogen has announced new data showing that aducanumab-avwa (Aduhelm) injection 100 mg/mL for intravenous use continued to significantly reduce 2 key Alzheimer disease (AD) pathologies in a 128-week extension phase of a phase 3 trial.
The 2 pathologies that were reduced in the long-term extension phase were amyloid beta plaques and plasma p-tau181. The data also showed that in both phase 3 trials, at 78 weeks, individuals with reduced levels of plasma p-tau181 had less clinical decline than those who did not see that reduction.
Data from the long-term extension showed that individuals with more effective amyloid beta clearance, defined as standardized uptake value ratio (SUVR) lower than 1.1 by 78 weeks, also had greater decreases in p-tau181 at week 128.
These findings indicate a potential of continued benefit of treatment in the longer term with continued reduction of amyloid beta plaques.
“These are meaningful findings, which further our understanding of amyloid and downstream biomarkers, such as p-tau 181, in Alzheimer’s disease and can help inform how long patients may benefit from treatment to reduce amyloid beta plaque,” Samantha Budd Haeberlein, PhD, senior vice president and head of neurodegeneration development at Biogen, said in a statement.
The findings from the phase 3 studies also showed that individuals with a reduction in plasma p-tau181, an exploratory endpoint, had less clinical progression in all 4 clinical endpoints that measured cognition and function, which were ADAS-Cog13, ADCS-ADL-MCI, CDR-SB, and MMSE, in both phase 3 clinical trials at week 78.
Additionally, in the placebo-controlled period, the incidence of cerebral edema (ARIA-E) in the 10 mg/kg group was 35.2%. The incidence was higher among those who were APOE ε4 carriers, at 43%, than those who were non-carriers, at 20.3%.
Although the majority of ARIA was asymptomatic, serious symptoms occurred in about 0.3% of individuals. Approximately 98.2% of ARIA-E resolved during the study, with a majority resolving within 12 to 16 weeks.
Biogen aims to further characterize ARIA and to understand the risk of ARIA better.
The long-term phase 3 extension study was presented at the International Conference on Alzheimer’s and Parkinson’s Disease, which is taking place in person in Barcelona, Spain, and virtually from March 15, 2022, to March 20, 2022.
An archived version of the presentation is published in the investor’s section of the Biogen website. Aducanumab-avwa is indicated for the treatment of AD. The treatment should be initiated in individuals with mild cognitive impairment or the mild dementia stage of disease.
There are no effectiveness or safety data on initiating treatment at earlier or later stages of the disease than were studied.
This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in individuals treated with aducanumab-avwa, and continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
Long-term phase 3 data show Aduhelm continues to reduce underlying pathologies of Alzheimer’s disease in patients treated for more than two years. Biogen. News release. March 16, 2022. Accessed March 16, 2022. http://media.biogen.com/news-releases/news-release-details/long-term-phase-3-data-show-aduhelmr-continues-reduce-underlying