Ionis Pharmaceuticals Inc. (IONS) and Otsuka on Tuesday shared positive topline results from their Phase 3 FUSION trial.

The trial evaluated ulefnersen, an investigational RNA-targeted medicine, in patients with amyotrophic lateral sclerosis (ALS) caused by mutations in the fused in sarcoma (FUS) gene (FUS-ALS).

ALS is a rare nervous system disease that destroys nerve cells in the brain and spinal cord, leading to progressive muscle weakness and paralysis.

Meeting the Primary Endpoint

The study successfully achieved its primary endpoint. Ulefnersen showed a statistically significant improvement in functional impairment and survival.

This was assessed using a joint rank analysis of time to death or permanent ventilation, time to rescue, and change in ALS Functional Rating Scale Revised (ALSFRS-R) score from baseline to Day 505, compared to a placebo.

These data provide evidence from the first placebo-controlled clinical study targeting the underlying genetic cause of FUS-ALS.

Ulefnersen, discovered and developed by Ionis, is the first treatment targeting this underlying cause and showing the potential to modify disease progression.

Secondary Endpoints and Safety

The FUSION study also recorded statistically significant improvements across key secondary endpoints.

These included the change from baseline in serum neurofilament light chain (NfL) and the time to death, permanent ventilation, rescue, or withdrawal due to disease progression.

These results further support ulefnersen's potential to improve the disease course in FUS-ALS patients.

The treatment also demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate.

“Ulefnersen is the first investigational medicine to demonstrate a statistically significant benefit in a Phase 3 trial using a prespecified joint-rank analysis that combines assessments of function and survival, supporting ulefnersen's potential to meaningfully modify disease progression,” said Holly Kordasiewicz, executive vice president, chief development officer, Ionis.

Future Steps and FDA Discussions

Further analyses of the data are planned to fully understand ulefnersen's potential.

Otsuka intends to urgently review the FUSION trial results with the U.S. Food and Drug Administration (FDA) and discuss potential expedited submission pathways for approval with other global health authorities.

Detailed results from the FUSION trial will be presented at an upcoming medical congress and submitted for publication in a peer-reviewed journal.

Otsuka licensed ulefnersen from Ionis in 2024. Under their agreement, Ionis received an upfront payment and is eligible for additional regulatory and sales milestones, plus tiered royalties on net sales.

IONS Price Action: Ionis Pharmaceuticals shares were up 0.88% at $45.29 at the time of publication on Tuesday. The stock is trading near its 52-week low of $44.20, according to market data.