FUS-ALS is a rare genetic form of ALS caused by variants in the FUS gene, accounting for less than one per cent of all ALS cases. FUS-ALS can be more common among people who develop ALS at a young age, presenting itself with an early-onset and faster rate of disease progression.

This Tuesday, September 22, 2026, Otsuka and Ionis Pharmaceuticals have announced positive topline results from the Phase 3 FUSION trial, evaluating the investigational therapy called ulefnersen for people with FUS-ALS. According to the companies, the trial met its primary endpoint and showed statistically significant evidence that ulefnersen may slow disease progression compared to placebo. Researchers assessed several outcomes over approximately 17 months, including survival, the need for permanent ventilation support, disease progression requiring additional intervention, and changes in daily function measured using the ALSFRS-R scale.

The trial also reported a statistically significant decrease in neurofilament light chain (NfL), a biomarker of nerve cell damage that is increasingly used in ALS clinical trials to assess whether a therapy may be reducing the underlying disease process. At a group level, higher NfL levels are generally associated with faster disease progression, and substantial reductions, often around 30% or greater, are typically considered meaningful. The companies have not yet reported how much NfL levels decreased during the trial. However, seeing a meaningful decrease in NfL alongside clinical benefits adds to growing evidence that changes in this biomarker can be indicative of whether a treatment is making a meaningful difference for people living with ALS.

It was also reported that ulefnersen demonstrated a favourable safety and tolerability profile, with most adverse events described as mild or moderate.

The results announced so far are high-level findings released by the companies, and as with any clinical trial announcement, we look forward to reviewing the full data as it becomes available. Additional analyses are ongoing, and detailed data will be presented at a future scientific conference and submitted for publication in a scientific journal. Researchers will also continue monitoring participants through the study’s open-label extension, where all participants receive ulefnersen.

Otsuka and Ionis have stated that they plan to discuss the results with regulatory agencies, including the U.S. Food and Drug Administration (FDA), to explore potential pathways toward approval. Information about regulatory review and access pathways in Canada is not yet available, and we will continue to share more as we hear from the companies and advocate for timely access.

While the full data are still being analyzed, these findings add to the most significant advances to date for the ALS community. Following the approval of Qalsody (tofersen) for SOD1-ALS, the results add to growing evidence that precisely targeting the biological drivers of ALS can lead to meaningful clinical benefit and may fundamentally change how certain forms of the disease are treated.

About ulefnersen

The FUS gene contains instructions for making the FUS protein, which helps cells manage the genetic messages needed to produce other proteins. In FUS-ALS, certain genetic variants cause abnormal FUS protein to build up inside motor neurons, contributing to their degeneration and disease progression.

Ulefnersen is an antisense oligonucleotide (ASO), a type of therapy that works by reducing the production of the abnormal FUS protein believed to drive disease in FUS-ALS. This is the same type of therapy as Qalsody (tofersen), which is approved for another genetic form of ALS, caused by the SOD1 gene.

Although preliminary, for a community that has long faced limited treatment options, the FUSION trial marks an encouraging step toward more personalized approaches to ALS treatment. ALS Canada will continue monitoring developments closely and will provide updates as additional data become available.

If you or a family member are affected by FUS-ALS, we encourage you to reach out to ALS Canada and our ALS National Genetic Counsellor at research@als.ca or genetics@als.ca. We can help you understand these results and what they may mean for you and your family.

Read more about the story behind ulefnersen from our colleagues at the MND Association, including the contributions of Jaci Hermstad, a young woman diagnosed with FUS-ALS whose advocacy and participation helped advance the research. (FUS-MND: The story so far…)

Read more about ALS genetics on als.ca/genehub.

Have any questions about ALS research or clinical trials? Stop by our monthly Ask Us Anything: Research session to learn more and chat with ALS Canada’s Research Team.

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