Tofersen

The trial is now recruiting in the UK at the following sites:

• Sheffield

Please contact the individual trial site, by clicking each site above, for more information on how to take part in the trial. 

Phase: Phase 3

Placebo Controlled: Yes - this means that people joining the trial could be randomly assigned to receive the placebo (dummy drug). 

Open-Label Extension: Yes - this means that all participants on the trial, regardless of whether they received the treatment or placebo, will have an opportunity to access the treatment once the randomised part of the trial is complete. 

Key eligibility criteria: This trial is only recruiting people with MND who have the SOD1 gene mutation, but do not have any symptoms of MND. Learn more about eligibility criteria. 

The first phase of the trial began in early 2016, recruiting 70 people with MND in the USA, Canada and Europe (including one centre in the UK). The drug was found to be safe and well tolerated. Early analyses showed that delivering the highest dose led to significant reduction of SOD1 protein levels in the cerebrospinal fluid (CSF) and showed signs of slower clinical progression.

The Phase 1/2 study results demonstrated proof-of-concept and proof-of-biology of tofersen.

The Phase 3 (VALOR) study explored the effects of the treatment in 108 people with SOD1-MND internationally, including the UK, over 28 weeks. The initial results were negative, with tofersen not significantly slowing disease progression as measured by ALSFRS-R. However, there were hints of benefit as measured by secondary endpoints, such as respiratory function and muscle strength. After the 28 weeks randomised phase, participants could enter the open label extension, so everyone was able to access the drug and the researchers could continue to collect data. 

Data from the open label extension of the trial was announced in June 2022. The results showed that participants who received tofersen earlier and longer had:

• Lowered levels of SOD1 protein, which stayed low throughout the 52 weeks, showing that the treatment is engaging with the biology it is meant to.
• Lowered levels of neurofilament light chain - a marker of nerve damage. The levels also stayed low over the 52 weeks possibly showing a reduction in nerve damage and disease progression.
• Lived longer than participants who started tofersen six months later, in the open label extension.

Read more about the trial or access the slides from the presentation in June 2022.

The results from this trial were formally published in September 2022 in the New England Journal of Medicine. 

November 2024- The National Institute for Health and Care Excellence (NICE), who decide which treatments become available on the NHS, has announced that they have changed their decision and will now appraise Tofersen through the Highly specialised Technologies (HST) route. This means that Tofersen will now get a fair assessment to decide if it will be accessible to people with SOD1-MND through the NHS. You can read more about what this means here.

March 2024 - The National Institute for Health and Care Excellence (NICE), who decide which treatments become available on the NHS, has decided to appraise Tofersen through the Single Technology Appraisal (STA) route rather than the Highly specialised Technologies (HST) route. It is highly unlikely that Tofersen will become accessible to people with SOD1-MND through the NHS if it is appraised through this route. You can read more about what this means and what the MND Association is doing.

February 2024 - Tofersen is recommended for approval for the treatment of SOD1 by the European Medicines Committee. This recommendation will now be reviewed by the European Commission who will make the final decision on approval for use for people with SOD1 MND in the EU. You can read more in a news story. 

September 2023 - The National Institute for Health and Care Excellence (NICE) have announced that its original decision stands and Tofersen will be considered on the single technology technology appraisal (STA) pathway. This looks at how beneficial and cost-effective Tofersen would be for the whole MND population, not just those with the SOD1 mutation in which Tofersen has been tested and reported to slow disease progression. The MND Association is considering its next steps. You can read more about the decision on the NICE website.

June 2023 - The National Institute for Health and Care Excellence (NICE) ruled that Tofersen would not be allowed into the highly specialised technology (HST) approval pathway. This pathway is designed specifically for drugs which have shown postivite results in trials on patients with rare conditions. The MND Association, people with MND and neurologists supported an appeal by pharmaceutical company Biogen.

April 2023 - The FDA have approved Tofersen (Qalsody) for the treatment of SOD1 MND. You can read more here.

March 2023 – FDA Advisory Committee outcome announced for Tofersen as a treatment for SOD1 MND in the United States. You can read more here.

Jan 2023 - The FDA announced that an Advisory Committee Meeting would be held to discuss the new drug application for Tofersen. The meeting is set for 22 March 2023. You can read more here.

Dec 2022 - Biogen announced that the EMA have accepted the Marketing Authorisation Application. You can read more here. 

Oct 2022 - Biogen announced that the FDA have extended the review period for Tofersen. An approval decision is now expected by 25 April 2023. You can read more here.

Sept 2022 - The results from the VALOR trial and its open label extension were published in the New England Journal of Medicine. You can read more about these results on our news story. 

July 2022 - Biogen announced that the FDA had accepted the New Drug Application and have granted priority review for Tofersen. An approval decision is expected by 25 January 2023. You can read more here. 

June 2022 - 12 month data from the open label extension was announced. You can read more here or access the presentation here.

• What does the FDA approval of Tofersen mean for the UK MND community?
• VALOR Biogen's Tofersen trial: a look at the open label extension data
• Emerging Gene-Targeting Therapies for SOD1-ALS
• Tofersen: antisense oligonucleotide drug shows promising results in Phase 1/2 trial 

The Scientific Advisory Council for the International Alliance of ALS/MND societies consists of 9 members from USA, UK (including MND Association's Head of Research - Nick Cole), Sweden, Italy, South Africa, China, Australia and Canada.

They produce briefing notes as a trusted source of information about current experimental treatments in clinical development, such as Tofersen.

These notes are produced after many rounds of careful discussion between the SAC members.

Read the briefing note for Tofersen.