Ulefnersen

Ionis, a US company that specialises in antisense (RNA-targeted) medicines, discovered and developed ulefnersen and ran the FUSION trial. In November 2024 Otsuka, a large Japanese drugmaker, took exclusive worldwide rights; Otsuka now leads regulatory filings, manufacturing and sales, while Ionis receives milestones and royalties.

In FUS-ALS, a changed FUS gene makes a harmful form of the FUS protein that builds up in motor neurons. Ulefnersen sticks to the FUS gene's messenger RNA so the cell makes less FUS protein, including the harmful form. It is injected into the spinal fluid so it reaches the brain and spinal cord directly.

FUSION, a placebo-controlled Phase 1-3 trial in 89 people, reported positive topline results on 22 September 2026. The companies say they will review the results with the FDA and other regulators to look for a faster (expedited) route to approval. No approval application had been announced as of 5 November 2026.

The main goal combined three things: time to death or permanent breathing support, time to needing rescue treatment, and change in the ALSFRS-R function score over about 72 weeks. In the 73 people in the main analysis, ulefnersen did significantly better than placebo (p=0.0005), and blood neurofilament (a nerve-damage marker) also improved. These are company topline results; the companies have not yet said how many points of ALSFRS-R were saved, and the full data have not been presented or peer reviewed. Earlier, in a 12-person open-label case series, most people still declined, though two did unusually well.

This is the most favourable result reported. See all key studies for the full picture.

FUS-ALS is rare (about 0.6% of people with ALS) but often starts young and progresses fast. You need a genetic test showing a FUS mutation to be eligible. The drug is not being studied in other forms of ALS.

Otsuka and Ionis said they will move quickly to review FUSION with the FDA and other regulators, and will present detailed results at a medical meeting and submit them to a journal "in the coming months". They have not given a date for an approval application.

FUSION has finished enrolling. In September 2026 Otsuka opened a global early access programme for people with a confirmed FUS-ALS genetic diagnosis who cannot join a trial. Requests must come from the treating doctor, not from patients or families, and each case still needs regulatory, ethics and treatment-centre approvals, so timing varies.

• FUSION (NCT04768972) active not recruiting · USA, Canada, Europe, Brazil, Japan, South Korea, Taiwan