Otsuka-Ionis ALS Drug Candidate Meets Phase 3 Goal; Seeks Expedited Approval

A drug candidate for amyotrophic lateral sclerosis (ALS) jointly developed by Otsuka Pharmaceutical and Ionis Pharmaceuticals met its primary endpoint in a phase 3 trial.

According to Fierce Biotech on the 22nd local time, the companies confirmed the results in the “FUSION” phase 3 trial involving 89 patients with ALS caused by FUS gene mutations.

FUS-ALS is a rare disease that accounts for approximately 0.6% of all ALS cases. Children and adolescents make up a relatively large proportion of patients, and younger patients may develop respiratory failure and die within 1 to 2 years after symptom onset.

Ulefnersen, the candidate designed by Ionis, is an RNA-targeting molecule that works by reducing production of the FUS protein, which causes motor neuron degeneration. The phase 3 trial provided evidence that it slows disease progression.

The 73 patients included in the primary analysis showed significantly better results than the placebo group on the primary endpoint, which assessed functional impairment and survival at week 72. The endpoint analyzed the ALS Functional Rating Scale, time to rescue therapy, and time alive without ventilatory support.

The trial also met its secondary endpoints. Ulefnersen showed statistically greater effects than placebo on changes from baseline in a neurodegeneration biomarker and on time to death, permanent ventilation, rescue therapy, or discontinuation due to disease progression. Safety and tolerability were also favorable, and most adverse events were mild to moderate.

John Kraus, Otsuka’s chief medical officer (CMO), said in a statement, “We will work closely with health authorities to urgently advance ulefnersen.” In 2024, Otsuka paid Ionis a $10 million upfront payment to secure worldwide rights to the candidate and assumed responsibility for global regulatory affairs and commercialization.

However, the commercial opportunity is limited because of the rarity of FUS-ALS. Guggenheim Securities analysts projected in an investor note on the 14th that Ionis’ ulefnersen sales, for which it receives sales royalties, will reach $14 million in 2030 and $16 million in 2036.