New data evaluating the treatment effect of aducanumab-avwa demonstrated a positive correlation between plasma p-tau reduction and less cognitive and functional decline in Alzheimer disease.
An independent lab conducted a prespecified analysis of approximately 7000 plasma samples from more than 1800 patients in the phase 3 EMERGE (ClinicalTrials.gov Identifier: NCT02484547) and ENGAGE (ClinicalTrials.gov Identifier: NCT02477800) trials. Findings from both studies showed that treatment with aducanumab-avwa resulted in significant reductions in plasma p-tau181 in a dose- and time-dependent manner compared with placebo.
In the EMERGE trial, patients treated with aducanumab-avwa high-dose achieved a 13% reduction in p-tau from baseline compared with an 8% increase for placebo (P <.001). In the ENGAGE trial, patients treated with aducanumab-avwa high-dose achieved a 16% reduction in p-tau from baseline compared with a 9% increase for placebo (P <.001).
In both studies, there was a positive correlation between plasma p-tau181 reduction and less clinical decline in all 4 clinical outcome measures. The following are the correlation values across these outcome measures for EMERGE and ENGAGE, respectively:
- Clinical Dementia Rating Sum of Boxes Score (CDR-SB): R =0.11 (P =.0166) and R =0.14 (P =.0005);
- Mini-Mental State Examination (MMSE): R = -0.21 (P <.0001) and R =-0.15 (P =.0002);
- Alzheimer Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 13): R =0.17 (P =.0001) and R =0.15 (P =.0002);
- Alzheimer Disease Cooperative Study/Activities of Daily Living scale adapted for MCI (ADCS-ADL-MCI): R =-0.12 (P =.0086) and R =-0.14 (P =.0010);
- A positive correlation was observed between changes in plasma p-tau181 and amyloid beta positron emission tomography (PET) standardized uptake value ratio: R =0.38 (P <.0001) and R =0.42 (P <.0001).
“These data not only show an important link between the ability of [aducanumab-avwa] to clear amyloid beta plaque and reduce plasma p-tau levels, but also significantly correlate those reductions with slowing cognitive decline,” said Oskar Hansson, MD, PhD, Professor of Neurology at Lund University and Skåne University Hospital, Sweden, who led the oral late-breaker presentation at the Clinical Trials on Alzheimer’s Disease conference. “Having research from nearly two thousand patients provides invaluable insights into the dynamics of the interconnected pathologies within this complex disease.”
Biogen also shared data from its phase 3b EMBARK study (ClinicalTrials.gov Identifier: NCT04241068), which evaluated the effects of reinitiating treatment with aducanumab-avwa in patients with Alzheimer disease who discontinued aducanumab-avwa for an extended period of time (average length: 1.7 years). Results showed that the high-dose group maintained amyloid beta plaque reductions during the treatment gap period compared with the placebo group. The Company did note that the study had several limitations and further investigation was needed to better understand the impact of discontinuation from anti-amyloid treatment.
In June 2021, the Food and Drug Administration (FDA) granted accelerated approval to aducanumab-avwa (marketed under the brand name Aduhelm) for the treatment of Alzheimer disease. Aducanumab-avwa is a human monoclonal antibody that is derived from a de-identified library of B cells collected from healthy elderly subjects with no signs of cognitive impairment or cognitively impaired elderly subjects with unusually slow cognitive decline. The treatment, which is administered as a monthly intravenous infusion (every 4 weeks and at least 21 days apart), binds to aggregated β-amyloid and promotes removal of amyloid from the brain.
New phase 3 data show positive correlation between Aduhelm™ treatment effect on biomarkers and reduction in clinical decline in Alzheimer’s disease. News release. Biogen Inc and Eisai Co., Ltd. Accessed November 12, 2021. https://www.globenewswire.com/news-release/2021/11/11/2333013/0/en/New-Phase-3-Data-Show-Positive-Correlation-Between-ADUHELM-Treatment-Effect-on-Biomarkers-and-Reduction-in-Clinical-Decline-in-Alzheimer-s-Disease.html.