Phase 3 trial for drug to treat a rare genetic form of MND shows encouraging results

Ionis and Otsuka Pharmaceutical yesterday announced positive topline results from their FUSION clinical trial. The trial was of a drug called Ulefnersen, a genetic intervention designed to treat inherited FUS-MND.

What is FUS-MND?

About 90% of MND cases appear sporadically. However, around 10% can be linked to an inherited gene change which increases a person’s risk of developing MND. Inherited changes in a gene called FUS accounts for roughly of these genetically linked MND cases, which is less than 1% of all MND cases.

Unchanged, FUS protein is found in the nucleus of cells and plays a key role in the management and processing of other genes. When genetic changes lead to faulty FUS proteins being made, they can travel out the nucleus and form toxic clumps in the cytoplasm.

The FUS gene was identified as an MND linked gene in 2009. Inherited FUS-MND is usually a rapidly progressing form of MND and can affect people earlier in life than other forms usually do.

What is Ulefnersen and how does it work?

Ulefnersen is a type of intervention known as an antisense olugonucleotide (ASO). ASOs are small fragments of DNA that are inserted into the spine via lumbar puncture. These pieces of DNA attach to the changed FUS gene, preventing the instructions for the faulty protein from being read, and stopping it’s production by the cells. This personalised approach using ASOs has been seen before in MND with tofersen, the Medicines and Healthcare products Regulatory Agency (MHRA) approved ASO for .

What did the trial show?

The data from the trial has yet to be published. However, in a press release from Ionis and Otsuka Pharmaceutical, who jointly run the trial, they stated that the topline results were positive.

The trial tested Ulefnersen against a placebo and the press release states that the functionality and length of survival was better in those who had been given the drug. As with the trial of tofersen, they also recorded serum levels of the protein neurofilament light chain (NfL) on those on the trial and the release mentions changes from the baseline value. NfL acts as a scaffolding for neurons. As neurons break down in conditions like MND the NfL becomes loose and can be found in body fluids such as blood and spinal fluid. Increasing NfL levels indicate the continued breakdown of neurons while stabilising, or a reduction in how quickly the NfL levels increase can indicate a reduction or slowing in neuron breakdown.

What’s next?

We are waiting for publication of the data from the trial to help us understand more fully how positive the results are.

Before Ulefnersen can be made available on the NHS in Scotland as a treatment for inherited FUS-MND, it must be approved by both the MHRA and Scottish Medical Consortium (SMC) – National Institute for Health and Care Excellence (NICE) for the NHS in England, Wales and Northern Ireland.

The press release indicates that Ulefnersen has been granted Orphan status by the Food and Drug Administration (FDA) in America and the European Medicines Agency (EMA). This status can be given to medicines for rare conditions, offering incentives to drug companies to speed up the development of safe, life-saving treatments for patients who currently have few or no options.

Although the press release does not mention the MHRA or SMC, the pathway being followed aligns with that of tofersen, which was granted MHRA approval and is expected to be assessed by the SMC this year.

What does this mean for me?

Otsuka have opened an Early Access Programme (EAP) in certain countries for those who have received a confirmed diagnosis of FUS-MND but are unable to participate in an ongoing clinical trial. They must meet predefined eligibility criteria. To know if you carry this altered gene, you should speak to your MND Specialist Nurse or neurologist. Access to the EAP can only be requested by your neurologist. Family members, carers, MND Specialist Nurses or charities are unable to request access on an individual’s behalf.

More information about the EAP can be found online – Early Access Programs | Otsuka US.

The website does not yet state if the UK will be a country where EAP access is available. MND Scotland has reached out to Otsuka to clarify and will update this news item upon receiving further information.

These positive topline results provide further evidence, alongside tofersen, that personalised, targeted therapies are a viable route for treatment in MND. Although the number of people who could benefit from these specific ASO treatments are relatively small, it provides hope that we can utilise these approaches in the future to provide meaningful treatments for people with MND.

Further information

Otsuka/Ionis press release: Otsuka Announces Transformative Phase 3 FUSION Results for Ulefnersen, Bringing the FUS-ALS Community Closer to a Potential Targeted Treatment | Otsuka US

Otsuka EAP website: Early Access Programs | Otsuka US

MND Scotland tofersen update: NICE assessment of tofersen to begin in 2026 – MND Scotland

MND Scotland inherited MND information: 2026-09-Inherited-MND-final.pdf

MND Scotland LEARN 2025 – Fergal Waldron’s talk on FUS and its role in non-FUS-MND: Developing tests to improve access to MND therapies – Dr Fergal Waldron – YouTube