A rare mutation in a rare disease: that of the SOD1 gene in people with amyotrophic lateral sclerosis (ALS): in these patients, for the first time an experimental drug, tofersen, has been shown to be able to slow the decline in respiratory function, muscle strength and quality of life when given early. The data comes from a new 12-month analysis of the VALOR clinical trial and its open label extension (OLE), presented at the European Network to Cure ALS (ENCALS) conference in Edinburgh, Scotland.
I study
The new analysis compared the results between patients who were treated with tofersen since the start of the VALOR study and those who were treated six months later in the open-label extension phase, since they were initially in the placebo control arm. In all, 108 patients were enrolled, of whom 95 participated in the extension study. Considering the overall study population over the 12 months, the results are favorable for early treatment with tofersen. “Initial results at six months – and now at 12 months – show that tofersen was able to impact parameters of great importance to people with SOD1-ALS,” said Timothy Miller, MD, Ph.D., principal investigator of VALOR and co-director of the ALS Center at Washington University School of Medicine in St. Louis: “If approved, it will significantly change the lives of those affected by SOD1-ALS.”
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The majority of study participants survived without permanent ventilation (PV). The drug also reduced levels of neurofilaments, the proteins that proliferate in the blood and cerebrospinal fluid when neurons are damaged, and which are a marker associated with neurodegeneration. Maintained reductions in total SOD1 protein levels and plasma neurofilaments over time were 33% and 51% in the early-onset groups and 21% and 41% in the delayed-onset groups, respectively. “The combination of these biomarker findings and clinical outcome data – continue the researchers – offers further evidence of its potential in effectively slowing the progression of SOD1-ALS.”
ALS with SOD1 mutation
Mutations in the SOD1 gene are responsible for approximately 2% of the estimated 168,000 cases of ALS worldwide. In Italy, we are talking about 120-150 people. Those affected suffer from muscle weakness and atrophy, progressively lose the ability to move, speak, eat and breathe. The average life expectancy varies a lot and ranges from one to more than 20 years.
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Aisla’s appeal
The drug is an antisense molecule, which is a small molecule used to prevent or alter the production of proteins at various levels in cells. What does he do? It binds to SOD1 mRNA to degrade it and reduce its synthesis. For Aisla – Italian Association of Amyotrophic Lateral Sclerosis, it is the beginning of a new page of the disease. And he appeals for the drug to be available quickly for ALS SOD1 patients: “The result obtained is a very important result for the patient community, always awaiting progress that can guarantee therapeutic opportunities for all”.