QALSODY Receives FDA Approval: A Breakthrough in Genetic ALS Treatment

Biogen has secured U.S. FDA approval for QALSODY (tofersen) 100 mg/15mL injection, marking a significant milestone in neurodegenerative disease treatment. The drug targets amyotrophic lateral sclerosis (ALS) in adult patients carrying mutations in the superoxide dismutase 1 (SOD1) gene—representing the first therapeutic approach to address this specific genetic cause of the disease.

Clinical Evidence Supporting QALSODY’s Approval

The accelerated approval pathway was based on compelling biomarker data from clinical trials. Patients treated with QALSODY demonstrated a remarkable 55% reduction in plasma neurofilament light chain (NfL) levels, compared to a 12% increase in the placebo group. This distinction—a 60% difference in geometric mean ratios—provides measurable evidence of the drug’s neuroprotective potential.

The VALOR study, a 28-week randomized, double-blind, placebo-controlled trial, enrolled 108 participants aged 23 to 78 years with confirmed SOD1 mutations. Patients received either QALSODY 100 mg (72 patients) or placebo (36 patients) over 24 weeks through a regimen of three loading doses followed by five maintenance doses. The primary analysis population (n=60) showed slower functional decline on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) with QALSODY treatment, though statistical significance was not achieved in this subset.

Understanding Neurofilament as a Biomarker

Neurofilaments serve as critical indicators of neuronal integrity. When neurons sustain damage, these proteins are released into circulation, making them valuable markers for tracking neurodegeneration. The substantial reduction in plasma NfL observed with QALSODY treatment suggests meaningful preservation of neural tissue, providing a mechanistic rationale for the drug’s therapeutic potential.

Safety Considerations

Clinicians must remain vigilant regarding serious neurologic adverse events associated with QALSODY, including myelitis, radiculitis, papilledema, elevated intracranial pressure, and aseptic meningitis. Should patients develop symptoms consistent with these conditions, immediate diagnostic evaluation and appropriate management are warranted, potentially requiring treatment interruption or discontinuation.

The most frequently reported adverse reactions occurring in ≥10% of treated participants—appearing more frequently than in placebo recipients—included pain, fatigue, arthralgia, elevated CSF white blood cells, and myalgia. Baseline medications such as riluzole (taken by 62% of study participants) and edaravone (8% of participants) were permitted during the trial.

Future Confirmatory Studies

While QALSODY gained approval through the accelerated pathway, continued market authorization may depend on clinical benefit confirmation from ongoing trials. The Phase 3 ATLAS study, evaluating QALSODY in presymptomatic SOD1-ALS patients, will serve as the definitive confirmatory investigation, potentially expanding the drug’s applicability to earlier disease stages.

Implications for the ALS Community

This approval expands the therapeutic arsenal for genetically-defined ALS, joining SPINRAZA as an Ionis-discovered medicine targeting rare neurodegenerative conditions. The development represents years of molecular research focused on RNA-based therapeutic approaches, opening pathways for similar genetic intervention strategies in other neurological disorders.