Otsuka Pharmaceutical Development & Commercialization (OPDC), Otsuka Pharmaceutical, and Ionis Pharmaceuticals have reported encouraging top-line data from the Phase III FUSION trial.
The trial is to assess an investigational therapy, ulefnersen, to treat people with a genetic form of amyotrophic lateral sclerosis (ALS) known as fused-in sarcoma (FUS)-ALS.
The randomised, global, multi-centre, placebo-controlled, double-blind trial, conducted in participants diagnosed with FUS-ALS, a condition linked to mutations in the FUS gene, met its primary endpoint.
Ulefnersen showed a statistically significant improvement compared to placebo on a combined measure assessing functional impairment and survival.
This measure used joint rank analysis of time to death or permanent ventilation, time to rescue, and changes in ALS Functional Rating Scale Revised (ALSFRS-R) scores from baseline to Day 505.
The study’s secondary endpoints also favoured ulefnersen over placebo.
Results included statistically significant improvements in biomarkers such as serum neurofilament light chain, and in composite measures such as time to death, permanent ventilation, use of rescue interventions, or withdrawal due to disease progression.
Ulefnersen’s safety profile in the study indicated that most adverse events were mild or moderate in severity.
Otsuka executive vice-president and chief medical officer John Kraus said: “Today’s Phase III FUSION topline results mark a major milestone for people living with FUS-ALS, reshaping what is possible for a community that has long faced this devastating disease with limited treatment options.
“As the first FUS-ALS clinical trial to meet its primary endpoint, FUSION provides compelling evidence that a targeted genetic approach may help alter the course of disease.
“We are committed to working closely with health authorities to advance ulefnersen with urgency and scientific rigour and remain committed to advancing meaningful treatments for patients with significant unmet needs across neurology and rare diseases, including ALS.”
Otsuka and Ionis intend to discuss the findings with the US Food and Drug Administration (FDA) and other health authorities to explore expedited regulatory submission pathways.
The companies are planning additional analyses of the data and anticipate sharing further results, including from an ongoing open-label extension, at a future medical congress and through publication.
FUS-ALS is a rare and often rapidly progressing form of ALS, with no currently approved therapies that directly address its genetic cause.
Before this, OPDC and Otsuka Pharmaceutical reported expanded Phase IIIb results for Simtriyo (centanafadine) in adults with attention-deficit/hyperactivity disorder (ADHD) and comorbid anxiety disorders.
