Ionis Pharmaceuticals Announces Topline Results from Phase 2 Celia Study of Diranersen

Published: 2026-05-14 17:20:42 ET IONS

Published on 05/14/2026 at 05:20 pm EDT

Ionis Pharmaceuticals, Inc. announced that its partner, Biogen, shared compelling 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 randomized Phase 2 study of a tau-directed therapy demonstrating both robust biomarker impact and cognitive benefit in early AD. Based on the strength of the biomarker and efficacy data, Biogen plans to advance diranersen to registrational development; CELIA did not meet its primary endpoint assessing dose response.

Robust reductions in tau pathology were observed across all studied doses, with results generally consistent with those observed in the Phase 1b study. Pre-specified analyses of cognitive endpoints demonstrated slowing of clinical decline across all studied doses, particularly at the lowest dose. The safety and tolerability profile of diranersen was generally consistent with the Phase 1b study.

Data will be presented at the Alzheimer?s Association International Conference (AAIC) 2026 and other upcoming scientific congresses. 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. 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.

Diranersen (IONIS-MAPTRx/BIIB080) is an investigational antisense oligonucleotide (ASO) therapy designed to target microtubule-associated protein tau (MAPT) mRNA to reduce the production of tau protein. Abnormal accumulation of tau in the brain is a hallmark of Alzheimer?s disease (AD) associated with neurodegeneration and cognitive decline. Diranersen is being investigated as a potential treatment for early AD.

In 2025, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to diranersen for the treatment of AD. In December 2019, Biogen exercised a license option with Ionis Pharmaceuticals and obtained a worldwide, exclusive, royalty-bearing license to develop and commercialize diranersen. Diranersen was discovered by Ionis.

CELIA is a global Phase 2 randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy, safety and tolerability of diranersen in individuals with early Alzheimer?s disease (AD). The study enrolled 416 participants with mild cognitive impairment due to AD or mild AD dementia. All participants enrolled in CELIA had not previously received anti-amyloid therapy.

The study evaluated three doses of diranersen administered intrathecally over a 76-week placebo-controlled treatment period: 60 mg every 24 weeks, 115 mg every 24 weeks and 115 mg every 12 weeks. The primary endpoint of CELIA was assessment of dose response for change from baseline on the Clinical Dementia Rating?Sum of Boxes (CDR-SB) at Week 76. Secondary and exploratory endpoints included additional clinical, biomarker and imaging measures, including cerebrospinal fluid tau biomarkers and tau positron emission tomography (PET).

An ongoing long-term extension (LTE) study is continuing to evaluate the long-term safety, tolerability and durability of diranersen in early AD.