Ionis announces positive results for phase 3 FUSION study

Ulefnersen was studied in the FUSION study, which was carried out at 25 centres worldwide, including multiple TRICALS centres. A total of 95 people with FUS-ALS took part in the study. On September 22, 2026 Ionis Pharmaceuticals, the sponsor of the study, and Otsuka Pharmaceutical Development & Commercialization announced positive results for the FUSION study. The results show that ulefnersen significantly improves functioning and has a positive effect on survival. People who received the drug lived longer, or were able to delay starting permanent ventilation, compared with those who received a placebo (a drug with no active substance).

Leonard van den Berg, chair of TRICALS and Principal Investigator in the study:

It’s fantastic news that the FUSION trial has produced positive results. Ulefnersen builds on the experience with Tofersen, which was already a breakthrough for people with the SOD1 form of ALS back in 2022. The fact that there may now also be a drug for FUS-ALS that appears to improve the course of the disease gives us hope for the development of similar treatments for other inherited forms of ALS. It also confirms that ALS is indeed a treatable disease.

What is FUS-ALS?

ALS is caused by a change in one or more genes. FUS-ALS is an inherited form of ALS in which changes in the Fused in Sarcoma (FUS) gene play a role. It occurs in around 0.6% of all people with ALS. FUS-ALS is a faster-progressing variant of the disease, with people generally dying sooner after the first symptoms appear. On average, this form of ALS occurs more often in young people: a FUS change is the cause in around half of all children and young people with ALS. At present, there is still no approved treatment for FUS-ALS.

How ulefnersen works

Like Tofersen, ulefnersen is an antisense oligonucleotide: an artificial piece of genetic material (RNA) that binds specifically to the substance that carries signals from the FUS gene. The drug is administered via a lumbar puncture, so that it reaches the central nervous system directly. This inhibits the production of the faulty FUS protein, which, in FUS-ALS, accumulates in the nerve cells that control the muscles (motor neurons) and causes damage to those cells.

Next steps

Ulefnersen has not yet been approved by the FDA or the EMA, the American and European regulatory bodies that determine whether medicines may be brought to market. IONIS and Otsuka are aiming to set the regulatory approval processes in motion as quickly as possible, with the goal of making the drug widely available to patients. It is not yet clear how quickly the drug will reach the market.