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NewsA first for FUS-ALS treatment: Ulefnersen, an antisense oligonucleotide targeting the FUS gene mutation, met its primary endpoint in the Phase 3 FUSION trial — marking the first placebo-controlled evidence for a genetically targeted ALS therapy. The drug showed statistically significant improvement in a composite measure of functional decline and survival, with a favorable safety profile. Regulators are next in line as Otsuka and Ionis plan expedited submissions.
A historic win for a devastating disease
Otsuka Pharmaceutical and Ionis Pharmaceuticals announced that ulefnersen — an investigational antisense oligonucleotide (ASO) — met its primary endpoint in the Phase 3 FUSION trial for FUS-ALS, a rare and rapidly progressive genetic subtype of ALS. This marks the first time a placebo-controlled trial has demonstrated benefit for a therapy targeting the underlying genetic cause of the disease.
The trial enrolled patients in a 72-week randomized, double-blind period followed by an open-label extension. The primary endpoint used a joint-rank analysis combining time to death or permanent ventilation, time to rescue, and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Ulefnersen showed statistically significant benefit over placebo (P = .0005). Secondary endpoints — including reductions in serum neurofilament light chain (NfL) and a composite time-to-event measure — also favored treatment, with most adverse events being mild or moderate.
Key Takeaways
Why it matters: FUS-ALS has no approved targeted therapies, leaving patients — especially children — with few options. These results could pave the way for expedited regulatory review and a potential new standard of care for one of ALS's most aggressive forms.