Ionis recently announced that its partner Biogen has shared topline results from the phase 2 CELIA study evaluating diranersen (IONIS-MAPTRx/BIIB080), an investigational antisense oligonucleotide (ASO) therapy targeting tau, in individuals with early Alzheimer’s Disease (AD). The CELIA results provide the first evidence from a randomised phase 2 study of a tau-directed therapy demonstrating both robust biomarker impact and cognitive benefit in early AD.

Holly Kordasiewicz, PhD, Executive Vice President, Chief Development Officer, Ionis, said, “We are highly encouraged by the topline results from CELIA, which underscore the potential of targeting tau to meaningfully impact patient outcomes in early Alzheimer’s Disease. These findings represent an important advancement for the field and underscore the impact of Ionis’ growing neurology portfolio, which now includes 13 medicines in clinical development including 6 that are wholly owned. We’re proud to have discovered diranersen and are deeply grateful to everyone who made this research possible.”

Pre-specified analyses of cognitive endpoints demonstrated slowing of clinical decline across all studied doses, particularly in participants receiving the lowest dose of diranersen, 60 mg administered every 24 weeks. Diranersen also demonstrated robust reductions in both cerebrospinal fluid (CSF) tau and tau pathology, as measured by Positron Emission Tomography (PET), across all studied doses, with reductions maintained throughout the dosing period. CELIA did not meet its primary endpoint assessing dose response for change from baseline on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at week 76.

Priya Singhal, MD, MPH, Executive Vice President and Head of Development, Biogen, said, “In CELIA, we believe we have seen an unprecedented and compelling confluence of efficacy and biomarkers results from a tau-directed agent in a randomised early Alzheimer’s Disease study. We are excited by these phase 2 data, which give us the confidence to advance diranersen to registrational development. We look forward to engaging with regulators and the broader Alzheimer’s disease community on next steps. I would like to thank the patients, families, investigators, and study teams who participated in this pioneering study.”

The safety and tolerability profile of diranersen across all studied doses was generally consistent with the phase 1b study and the known profile of diranersen to date. The incidence of Adverse Events (AEs) was comparable across dose groups, with a higher incidence of Serious Adverse Events (SAEs) observed at the highest dose studied.

CELIA is a pioneering study evaluating diranersen, a first-in-class investigational ASO designed to reduce the production of tau protein at its source in early AD. While tau plays an important role in the normal function of brain cells, in AD, abnormal tau can accumulate and form intracellular tangles that contribute to neurodegeneration and cognitive decline. Unlike many investigational approaches that have focused on targeting extracellular tau, diranersen is designed to reduce both extracellular and intracellular tau.