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.
Presymptomatic ALS, as the name implies, refers to the period during which a person has early signs of ALS, 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 ATLAS trial will enroll about 150 adults with SOD1 mutations that are typically associated with rapid disease progression. In the first part of the trial, participants will not receive any treatment, but they will undergo monthly screenings of NfL levels.
If screenings reveal a rise in NfL levels of at least 10 picograms (pg) per mL, such that total levels are at or above 44 pg/mL, participants will be enrolled in the next portion of the study, during which they will be given either tofersen (100 mg) or a placebo.
Individuals who develop clinically manifest ALS during this part of the trial will be allowed to move to an open-label part of the trial during which all participants will receive tofersen.
The study’s primary efficacy endpoint — its main measurement of treatment effectiveness — is the proportion of participants who develop clinically manifest ALS within a year of randomization.
It is conceivable that some people will develop clinically manifest ALS before an increase in NfL levels is evident. These individuals also would be randomized to either tofersen or placebo.
Participants in the study will be treated for up to two years.
The overall objective of ATLAS is to evaluate whether preysmptomatic initiation of tofersen can delay emergence of clinically manifest ALS and/or slow the decline in function after the emergence of clinically manifest ALS.
Macquarie University
Richard Gan +61298123739 richard.gan@mq.edu.au
