Ulefnersen Meets Phase 3 Primary Endpoint in FUS-ALS

Ionis Pharmaceuticals and Otsuka Pharmaceutical Development & Commercialization announced positive topline results from the phase 3 FUSION trial of ulefnersen, an investigational RNA-targeted medicine for amyotrophic lateral sclerosis (ALS) caused by mutations in the fused in sarcoma (FUS) gene. The trial met its primary endpoint assessing functional impairment and survival compared with placebo.

FUSION is a global, multicenter, randomized, double-blind, placebo-controlled phase 1-3 trial of intrathecally administered ulefnersen in patients with FUS-ALS. During the 72-week double-blind portion, participants received ulefnersen or placebo before entering an open-label extension in which all participants received ulefnersen. The primary analysis population included 73 patients.

The primary endpoint used a joint-rank analysis incorporating time to death or permanent ventilation, time to rescue, and change from baseline in the ALS Functional Rating Scale-Revised score through day 505. Ulefnersen produced a statistically significant improvement compared with placebo (P = 0.0005). Meeting a prespecified disease-progression criterion allowed participants to enter the open-label period early and was classified as rescue.

The companies also reported statistically significant improvements in serum neurofilament light chain levels and time to death, permanent ventilation, rescue, or withdrawal because of disease progression. Ulefnersen was described as having a favorable safety and tolerability profile, with most adverse events classified as mild or moderate. The release did not provide effect sizes, detailed secondary-endpoint results, or adverse-event rates.

The findings remain topline results. Ionis and Otsuka plan additional prespecified and exploratory analyses, presentation at a future medical congress, and submission to a peer-reviewed journal. Otsuka also plans to discuss the data with the FDA and other health authorities regarding potential expedited submission pathways. Ulefnersen has FDA Fast Track designation for FUS-ALS and orphan designation for ALS but remains investigational.

Source: Ionis Pharmaceuticals, Inc. Ionis announces positive topline results from Phase 3 FUSION study of ulefnersen marking significant milestone in advancing first potential disease modifying treatment for FUS-ALS. News release. Ionis Pharmaceuticals, Inc.; September 22, 2026. Accessed September 23, 2026.