BIIB080 Significantly Reduces Tau Protein in Early Alzheimer Disease


By the end of the open label long-term extension study, BIIB080 reduced aggregated tau pathology in all dose groups assessed across all brain composites.

Priya Singhal, MD, MPH, executive vice president, head of development at Biogen

Priya Singhal, MD, MPH

Biogen recently presented new promising results from the phase 1b clinical trial that demonstrated a reduction of soluble tau protein in cerebrospinal fluid (CSF) with treatment of BIIB080 in patients with early Alzheimer disease (AD). BIIB080, an investigational antisense oligonucleotide (ASO) therapy, is the first to display a depletion of this magnitude in tau PET across the regions of the brain.1,2

Results demonstrated that BIIB080 reduced biomarkers of soluble tau in CSF (t-tau and p-tau181) in a dose-dependent and sustained manner. By the end of the long-term extension (LTE), all dose groups showed approximately a 60% reduction from baseline CSF tau levels. Notably, BIIB080 also reduced aggregated tau pathology as early as week 25 up until the end of the LTE at week 100, including patients who started on placebo and were given BIIB080 at week 25 in the LTE.

“Given the complexity and urgent unmet need in Alzheimer’s disease, Biogen continues to evaluate multiple modalities and targets including tau, which is believed to play a critical role in cognitive decline,” said Priya Singhal, MD, MPH, executive vice president, head of development at Biogen, said in a statement.1

The findings were presented at the 2023 International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders (AD/PD), held March 28-April 1, in Gothenburg, Sweden. The primary end points of the phase 1b trial and its open-label LTE were the safety and tolerability of multiple dose levels of BIIB080 in patients with mild AD (n = 46), with biomarker data as an exploratory endpoint. Aggregated tau pathology was assessed and measured by PET in all brain composites. The majority of adverse events in the study were mild or moderate in severity, with headache, back pain, and post-lumbar puncture syndrome (PLPS) as the most commonly reported in patients.

"These encouraging findings are the latest example of the potential of the Ionis RNA-targeting platform to selectively modulate proteins linked to CNS disease," said Eugene Schneider, MD, executive vice president and chief clinical development officer at Ionis, said in a statement.2 "Ionis is pioneering potential therapies for serious neurological diseases with high unmet need. In addition to Alzheimer's disease, our clinical stage neurology programs include ATTR polyneuropathy, ALS, Alexander disease, Parkinson disease and Angelman syndrome."

Tau protein can form “tangles” in patients with Alzheimer disease which progressively accumulate in regions of the brain that are involved in cognition.3 Accumulation of the tangles has shown to promote damage in brain cells and mortality. Hence, BIIB080 aims to target microtubule-associated protein tau (MAPT) mRNA and prevent the production of the tau protein.1

In other news, the phase 2 CELIA study of BIIB080 (NCT05399888) is currently in progress and has begun participant recruitment of patients with mild cognitive impairment or mild dementia because of AD in the United States.1 Researchers will investigate if BIIB080 can slow the worsening of AD more than placebo and what dosage of the treatment slows worsening of AD the most. The Clinical Dementia Rating-Sum of Boxes (CDR-SB) will be used to measure dementia symptoms in patients. Patients enrolled will be given a low dose or high dose of BIIB080 or a placebo as an injection into the fluid around the spinal cord. Participants will be in the study for 105 weeks, or a little over 2 years, which includes the time for screening and follow-up periods.

In December 2019, Biogen used an option for license with Ionis and secured a worldwide, exclusive, royalty-bearing license for the development and commercialization of BIIB080 (tau ASO).1

1. New data presented at AD/PD™2023 show IONIS-MAPT Rx (BIIB080) substantially reduced tau protein in patients with early-stage Alzheimer's disease. News Release. Biogen. Published March 29, 2023. Accessed April 4, 2023.
2. New data presented at AD/PD™2023 show IONIS-MAPT Rx (BIIB080) substantially reduced tau protein in patients with early-stage Alzheimer's disease. News Release. Ionis Pharmaceuticals. Published March 29, 2023. Accessed April 4, 2023.
3. Tau Topic Sheet. Alzheimer Association. Accessed April 4, 2023.
4. A Study to Assess if BIIB080 Can Change Clinical Dementia Rating-Sum of Boxes Scores, and BIIB080 Safety and Tolerability When Injected Into the Cerebrospinal Fluid of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age (CELIA). U.S. National Library of Medicine. Accessed April 4, 2023.
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