Jacifusen

An investigational therapy for ALS caused by mutations in the FUS gene (also known by the generic name ulefnersen). It works by reducing the toxic FUS protein that accumulates in motor neurons. In September 2026, Ionis and Otsuka reported that its Phase 3 FUSION trial met its main goal.

Jacifusen reduces the amount of toxic FUS protein in nerve cells. In FUS-ALS, a gene mutation causes the body to make a toxic form of the FUS protein that builds up and damages motor neurons. This drug works by blocking the instructions that tell cells to make this harmful protein.

In 12 people treated through expanded access, the most common side effects were back pain (50%), headache (33%), nausea (25%) and headache after the spinal tap (25%). Half had a temporary rise in spinal fluid cell counts or protein. Of the 12, 2 died, and the investigators judged both deaths unrelated to the drug^[4]. Full safety results from the Phase 3 FUSION trial have not been presented yet. Tell your doctor about any unusual symptoms.

Jacifusen is given as an injection into the spinal fluid (intrathecal injection). In the Phase 3 FUSION trial it is given every 12 weeks, with an extra dose at week 4^[5]. Treatment takes place at specialized medical centers. In FUSION, the placebo-controlled part lasted 72 weeks.

Jacifusen is currently in phase 3 clinical trials for Amyotrophic Lateral Sclerosis. It has not yet received FDA approval.

FUS-ALS is a form of amyotrophic lateral sclerosis caused by mutations in the FUS gene. It accounts for a small percentage of familial ALS cases and is the most common genetic cause of juvenile-onset ALS (diagnosed before age 25). The FUS protein normally helps process RNA in nerve cells, but mutant FUS accumulates in toxic clumps that damage and kill motor neurons. FUS-ALS often progresses rapidly, making targeted therapies especially urgent.

Both are antisense oligonucleotides delivered by intrathecal injection, but they target different genes. Tofersen targets SOD1 mRNA for SOD1-ALS patients, while jacifusen targets FUS mRNA for FUS-ALS patients. They cannot be used interchangeably because each is designed to bind a specific genetic sequence. Tofersen is FDA-approved (2023), while jacifusen is not yet approved, although its Phase 3 trial reported positive topline results in September 2026.

Not through a prescription, because it is not FDA-approved. On September 22, 2026 Otsuka announced a global early access program for ulefnersen. It is for people with a confirmed genetic diagnosis of FUS-ALS who cannot join a clinical trial, and a treating physician must make the request; Otsuka does not accept requests from patients or carers. Availability and timing vary by country^[3].

In 12 people with FUS-ALS treated through expanded access, the most common side effects were back pain, headache, nausea and headache after the spinal tap. Of the 12, 2 died, and the investigators judged both deaths unrelated to the drug. Most kept declining, though function recovered in 1 person after 10 months and another stayed free of symptoms. This was not a controlled study. The Phase 3 FUSION trial, which reported positive topline results in September 2026, provides the controlled evidence^[4].

FUSION is the Phase 3 trial of jacifusen (ulefnersen) in people with FUS-ALS. It compared the drug with placebo over a 72-week double-blind period. On September 22, 2026, Ionis and Otsuka announced that it met its primary endpoint in the main analysis group of 73 patients. Full results are expected at a medical meeting, and the companies plan to discuss next steps with the FDA. Your neurologist can help you check ClinicalTrials.gov for current studies.

Yes. Jacifusen and ulefnersen are names for the same molecule, also known by its development code ION363. The drug was originally referred to as ION363 during early development by Ionis Pharmaceuticals. Ulefnersen is the official generic name that Ionis and Otsuka use, and jacifusen is the name used in early reports.