Tofersen: antisense oligonucleotide drug shows promising results in Phase 1/2 trial

A recent press release by the pharmaceutical company Biogen reported preliminary results from an ongoing clinical trial investigating a form of precision therapy in people with SOD1-related MND. This drug, known as tofersen, is now in the final stages of Phase 1/2 testing in centres across the world, including Sheffield in the UK.

Tofersen is an antisense oligonucleotide (ASO), designed to prevent the faulty disease-causing protein from being made. Proteins, the building blocks of the body, are created from our genetic information (DNA) via its photocopy (RNA). If a piece of DNA is damaged, the RNA will also be damaged, leading to formation of a faulty protein and creating issues in the body. Tofersen is a synthetically-created RNA directed to stick to the faulty photocopy (RNA) preventing it from making faulty proteins.

In order to create proteins, the building blocks of our body, a stretch of DNA first has to be copied to make an RNA molecule, which is then coded into proteins. When there is a mistake in the DNA instruction, this is copied onto the RNA and a faulty protein is created as a result, accumulating outside of the control centre (nucleus) of motor neurons. The antisense oligonucleotide works by targeting and attaching itself to the stretch of RNA with the mistake so that the protein cannot be formed, and therefore prevent accumulation of these outside the nucleus.

As the study is in its early stages, it is mainly focused on the safety and dose of the drug. However, the inclusion of a double blind design, a placebo arm and a relatively high number of participants (38 who received tofersen and 12 placebo) has helped to provide an insight into the drug’s functionality.

The study has shown that people receiving the highest dose of the drug (100mg) during the three month trial had significantly reduced amounts of SOD1 protein, compared to those taking the placebo, and signs that the progression of their MND had slowed down – measured by the ALSFRS-R disease progression rating scale, slow vital capacity and muscle strength.

A Phase 3 trial is already recruiting participants in the USA. This will explore the effects in a greater number of participants. In a separate clinical trial, a similar drug is also being investigated for its safety and, eventually, effectiveness, in people with C9ORF72-related MND – this trial plans to recruit people in the UK in the future.

Nick Cole
Dr Nick Cole, Head of Research at the MND Association

Dr Nick Cole, Head of Research at the MND Association, commented: “The data is encouraging and if the final outcomes are as positive as we hope, this would be a significant milestone in the fight against MND. This therapy would be the first targeted treatment for a specific type of genetic MND, bringing hope to people and families with one type of inherited MND.

“This study demonstrates that through continuing public support, collaboration and partnerships between charities, researchers and pharmaceutical companies we will find solutions to the difficult question of MND.

“Although this treatment may only be suitable for a relatively small proportion of people with MND, any positive outcome resulting in a therapy is hugely significant and would mean so much to a lot of people. 

“The hope is that this type of targeted technology could be applied to other genetic forms and, ultimately, pave the way to uncovering treatments for sporadic MND, which represents the vast majority of cases.”

7 thoughts on “Tofersen: antisense oligonucleotide drug shows promising results in Phase 1/2 trial

  1. Please talk in layman terms and add “inherited type mind” at the start of your posts. Do not buidpoples hopes only to be dashed at he bottom of the article!!

    • Dear Martin,

      Our aim is to inform the public about important findings in the field of MND research in an accurate manner, and it definitely isn’t our intention to build up hopes and then dash them. I appreciate that some articles might feel as if they are distant from finding a cure for MND, however, all of these findings are bringing us closer to finding THE treatment, step by step.

      As we mentioned at the end of the article, it is also important to remember that even though some drugs target specific genes, it doesn’t mean they are irrelevant to most people with MND, as these techniques might be key to treating all forms of the disease.

      Best Wishes,

      The Research Development Team

  2. […] Tofersen is an antisense oligonucleotide (ASO). ASOs are short sequences of synthetic RNA designed to target faulty RNA before it is expressed (made) into a faulty protein. Previous studies in SOD1 mouse models of MND demonstrated that expression of mutant SOD1 causes MND but when the gene is removed the disease does not develop. Other studies using rats and non-human primates showed that ASOs could cross the blood-brain barrier and were able to reduce the mutated form of SOD1 resulting in extended survival. A Phase 3 trial looking at the safety and effectiveness of tofersen is currently recruiting in the USA. Recruitment will begin in the UK later this year. A similar trial is in preparation for the C9ORF72 expansion. […]

  3. […] Tofersen was well tolerated with the greatest reduction in SOD1 levels observed in the CSF with the higest dose (100 mg). There was an improvement in clinical measures with an observed slowing of decline in function, respiration, and muscle strength. The treatment also showed a reduction in neurofilaments levels (an apparent marker of disease activity) compared with placebo. Results support the continued development of tofersen for treatment of SOD1-MND and is currently being recruited for Phase 3, VALOR. Read our previous blog post on toferson here. […]

  4. Tofersen I am on this treatment at Sheffield Hallamshire Hospital and I believe I am doing extremely well on it I have the drug monthly via a lumber puncture.All the staff are brilliant and I can’t prraise them highly enough

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