FDA approves medication tofersen for a specific form of ALS

Edited by, SNEHA MAVIS

FDA  approves medication tofersen for a specific form of ALS

Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, is a rare neurological disorder that affects motor neurons—the brain and spinal cord nerve cells that regulate voluntary muscular movement. The nervous system's ability to communicate with the muscles fails as the motor neurons diminish resulting in the muscles' deterioration and inactivity. It affects more than 200,000 people worldwide.

ALS symptoms and signs include weakness in the hands, legs, ankles, and feet as well as difficulty maintaining proper posture. Additionally, breathing, eating, and speaking difficulties are common in ALS patients.

As of now, ALS has no known treatment. Most persons with the condition die of respiratory failure in three to five years after being diagnosed. A mutation in the SOD1 gene causes about 20% of familial ALS cases. The FDA has approved Biogen's investigational antisense drug tofersen for individuals with SOD1 ALS.

SOD1-ALS: What is it?

The SOD1 gene mutation accounts for 10% to 20% of all familial ALS cases. SOD1-ALS is a rare inherited form of ALS that affects roughly 330 individuals in the US. The SOD1 gene produces an enzyme that adheres to copper and zinc molecules of the body and degrades harmful chemicals known as superoxide radicals.

What is the mechanism of tofersen?

An antisense oligonucleotide (ASO) called Tofersen is being studied as a potential therapy for SOD1-ALS. ASOs are short, synthetic nucleotide strings that are intended to modify gene expression by binding to target RNA. 

Mutations in the SOD1 gene lead the body to produce a toxic version of SOD1 protein in persons with SOD1-ALS. Motor neurons degrade as a result of this toxic version of the SOD1 protein, causing increasing muscular weakening. Tofersen is intended to bind to and destroy SOD1 mRNA in order to limit SOD1 protein synthesis.

Results of Phase 3

The consolidated 12-month results from the phase 3 VALOUR clinical study and its open-label extension (OLE) revealed reductions in neurofilament – a marker of neuronal injury and neurodegeneration. In addition, neurofilament levels in patients were reduced by 40–50% by tofersen. 

Numerous studies have shown that neurofilament levels are predictive of the progression of disease and survival, and higher levels are linked to a quicker reduction in clinical function and a shorter life span. The combined effect of these biomarker findings and clinical outcomes data supports tofersen's ability to successfully reduce the course of SOD1-ALS.

According to Biogen's press announcement, tofersen failed to achieve the main objective of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Tofersen, on the other hand, was found to reduce deterioration in motor skills, breathing capacity, muscle strength, and quality of life in persons with SOD1-ALS.