SOD1 antisense oligonucleotide - Tofersen (ATLAS Preventative Trial)

What does Tofersen do?

Tofersen is designed to treat familial MND that is caused by mistakes in the SOD1 gene. The drug uses an approach known as ‘antisense’. This means that the drug directly interferes with the faulty instructions for making SOD1 protein, thus stopping the production of the disease-causing substance.

Given that individuals with SOD1 mutations can be recognised as at-risk of developing ALS through genetic testing prior to onset of symptoms, tofersen represents a tremendous opportunity to determine if treatment in pre-symptomatic individuals could slow down disease progression.

ATLAS Preventative Trial

The primary objective of the ATLAS trial is 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 of motor neurone disease (pre-symptomatic carriers). The pre symptomatic phase refers to when a person displays early signs of MND, like nervous system damage, but does not have overt clinical signs of the disease. 

In ATLAS, the optimal time for treatment will be determined with the help of a biomarker called neurofilament light chain (NfL). NfL is a structural protein found in neurons that is released into the blood and other bodily fluids when nerve cells become damaged. Prior research has suggested that NfL levels start to increase in SOD1 carriers before clinically evident disease manifests.

The initial part of the trial involves monthly screening of NfL levels. Once these levels rise to a certain threshold, participants will progress to the next phase of the study, during which they will be assigned tofersen or a placebo. A placebo does not contain any active ingredients. If during the trial any participants develop clinical symptoms of motor neurone disease, they will be able to move to an open-label part of the trial where they are guaranteed to receive tofersen (there is no placebo at this stage of the trial). 

The study will also continue to evaluate the safety and tolerability of tofersen.

How can I take part in this trial?

This trial is open only to people with an identified SOD1 mutation. Trial sites and eligibility criteria are listed below. In order to take part in a clinical trial, you should first speak to your neurologist or MND Clinic.

Eligibility criteria

• Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved for inclusion by an external mutation adjudication committee.
• Participants with plasma NfL level less than the protocol-defined threshold.
• Participants who are clinically pre-symptomatic for ALS (i.e. must not have clinically manifest ALS).

Want to know more?

For more information visit clinicaltrials.gov