A phase 3 study of Otsuka and Ionis Pharmaceuticals’ amyotrophic lateral sclerosis (ALS) drug candidate has hit its primary endpoint, positioning the partners to talk to regulators about expedited approvals.
The Fusion clinical trial enrolled 89 people with ALS caused by mutations in the fused in sarcoma (FUS) gene. The rare, often rapidly progressive disease, which is called FUS-ALS, accounts for about 0.6% of ALS cases. FUS represents a higher proportion of ALS cases in juvenile and pediatric populations and can lead to respiratory failure and death within one to two years of symptom onset in younger patients.
Ionis designed ulefnersen, an RNA-targeted molecule, to lower production of the FUS protein that drives motor neuron degeneration in patients with the rare disease. The phase 3 trial generated evidence that the drug candidate slows disease progression.
The 73 patients in the primary analysis population performed significantly better on ulefnersen than on placebo against the primary endpoint, which assessed functional impairment and survival at Week 72. The endpoint analyzed performance on an ALS functional rating scale, time to rescue and ventilation assistance-free survival.
Ionis and Otsuka reported hits on secondary endpoints. Ulefnersen had a statistically bigger effect than placebo on the change from baseline in a neurodegeneration biomarker, as well as on the time to death, permanent ventilation, rescue or withdrawal because of disease progression. The partners called the safety and tolerability profile favorable, with most adverse events being mild to moderate in severity.
Otsuka intends to work “closely with health authorities to advance ulefnersen with urgency,” John Kraus, M.D., Ph.D., the company’s chief medical officer, said in a statement. The Japanese drugmaker paid Ionis $10 million upfront for worldwide rights to the drug candidate in 2024, assuming responsibility for global regulatory and commercialization activities.
The rarity of FUS-ALS limits the commercial opportunity. Ulefnersen revenues at Ionis, which will receive royalties on sales, will rise to $14 million by 2030 and reach $16 million by 2036, Guggenheim Securities analysts forecast in a Sept. 14 note to investors. To put the figure in context, the analysts predicted that the GSK-partnered hepatitis B drug Hibsago will generate $221 million for Ionis in 2026.