BIIB067 (Tofersen)

What does the drug do?

BIIB067 (Tofersen), developed by Biogen in collaboration with Ionis Pharmaceuticals, is specifically designed to treat familial MND caused by mistakes in the SOD1 gene. It uses an approach known as ‘antisense’, in which the drug directly interferes with the faulty instructions for making SOD1 protein, thus stopping the production of the disease-causing substance.

Phase 1/2 trial

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). To date, the drug has shown acceptable safety and tolerability. 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.

Phase 3 - VALOR

The Phase 3 (VALOR) study explored the effects in a greater number of participants in the UK (Sheffield and London) and internationally. The primary outcomes measured the change in the ALSFRS-R from baseline to week 28. In a press release published on 17 October 2021 Biogen announced their phase 3 trial for tofersen (VALOR) did not meet its primary endpoint. However, signs of reduced disease progression were seen across multiple secondary and exploratory endpoints, including respiratory function and reduced levels of SOD1 in the CSF. Additionally, the results of VALOR and the ongoing open label extension study showed that early access to tofersen led to less decline across secondary outcome measures. You can find out more about the trial here.

Those who completed the study were allowed to enroll in an open label extension study, where they can continue to take the drug. You can find out more here.

12 month 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, which is 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.

You can read more about the trial in a blog post here or access the slides from the presentation in June 2022 here.

The results from this trial were formally published in September 2022 in the New England Journal of Medicine. We wrote about these results in a news story.

Phase 3 - ATLAS

Phase 3 clinical trial, called ATLAS, will seek to determine the value and optimal timing to begin treatment with tofersen in people who have SOD1 gene mutations but have not yet started to show symptoms (pre-symptomatic carriers). This refers to when a person displays early signs of MND, like nervous system damage, but does not have overt clinical signs of the disease. The ATLAS trial will enroll about 150 adults with SOD1 mutations that are typically associated with rapid disease progression. Find out more here.

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

Latest News:

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 MedicineYou 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.

Oct 2021 - Biogen announced expansion of the eligibility for its ongoing early access programme to the broader SOD1-MND community. You can read more here.

The Scientific Advisory Council (SAC) Briefing Notes

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.

You can find the briefing note for NurOwn here.

Last updated: 17/10/2022

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