Topline announcement of Phase 3 trial results for FUS-MND appear promising

Yesterday, the companies Otsuka and Ionis announced the results of their Phase 3 trial of the genetic therapy, ulefnersen. Ulefnersen targets a rare form of MND caused by mutations in the FUS gene, which accounts for less than 1% of the MND population.

What the announcement tells us

The announcement reported that ulefnersen may slow disease progression compared to placebo. This was demonstrated by a statistically significant improvement in survival, time to permanent ventilation, disease progression requiring additional intervention, and changes in daily function measured using the ALSFRS-R scale.

The announcement also reported a statistically significant decrease in neurofilament light chain (NfL), a biomarker of nerve cell damage that is increasingly used in clinical trials to assess whether a therapy may be reducing the underlying disease process. However, no specific data has been provided on the extent of decrease.

Otsuka and Ionis also suggest that ulefnersen demonstrated a favourable safety and tolerability profile, with most adverse events described as mild or moderate.

Take-home message

So far, this update is promising. However, we still need to review the full data when it becomes available. When a clinical consensus has been formed, we will share this with you.

If the data for ulefnersen is as positive as it sounds, this announcement could add weight to the power of genetic therapies in MND subtypes, where we understand the genetic drivers of disease. For example, tofersen has recently been shown to be the first truly effective therapy to slow the progression of MND caused by mutations in the SOD1 gene.

What happens next?

The companies 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 the UK is not yet available, and we will continue to share more as we hear from the companies and advocate for timely access.

In the meantime, Otsuka, which owns the manufacturing and licensing rights for ulefnersen, has immediately opened an early access programme. This means clinicians can apply for their patients who have MND caused by mutations in the FUS gene to access ulefnersen ahead of it going through the regulatory process.

More about ulefnersen

Ulefnersen is an antisense oligonucleotide therapy. It is a similar kind of therapy to tofersen, which has been developed for SOD1-MND and has been shown to successfully slow disease progression in many people with SOD1-MND.

It is administered via lumbar intrathecal injection (an injection through a spinal tap directly into the cerebrospinal fluid) every 12 weeks.

Ulefnersen is only suitable for people with mutations in the FUS gene, which represents less than 1% of the MND population.