The FDA has approved Qalsody (tofersen) to treat patients with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). This is a significant development as Qalsody is the first drug specifically indicated for SOD1-ALS. ALS is a neurodegenerative disease that attacks and kills the nerve cells that control voluntary muscles. SOD1-ALS is a subtype of ALS that is associated with mutations in the SOD1 gene. It is estimated that less than 500 patients in the United States have SOD1-ALS.
Qalsody is a type of antisense oligonucleotide that is designed to reduce the synthesis of SOD1 protein by targeting SOD1 mRNA. The efficacy of Qalsody was tested in a 28-week clinical trial involving 147 patients with ALS-related weakness and a confirmed SOD-1 mutation. The trial was randomized, double-blind, and placebo-controlled, with a central laboratory confirming the presence of the mutation.
According to the clinical trial results, patients treated with Qalsody demonstrated a statistically significant reduction in plasma neurofilament light (NfL) concentration at Week 28 compared to those in the placebo group. NfL serves as a biomarker for axonal injury and neurodegeneration. The reduction in NfL levels observed in patients treated with Qalsody was consistent across all subgroups based on sex, disease duration since symptom onset, site of onset, and use of other medications for ALS treatment.
Healthcare professionals with experience in performing lumbar punctures are responsible for administering Qalsody intrathecally via spinal injection. The recommended dosage of Qalsody is 100 mg (15 mL) per administration. Patients are initially given three doses of Qalsody at 14-day intervals, followed by a maintenance dose of Qalsody once every 28 days.
It is important to note that Qalsody has been approved under an accelerated approval pathway, specifically for drugs that target serious medical conditions with unmet needs and where a drug has demonstrated efficacy against a surrogate endpoint that is reasonably likely to indicate clinical benefits for patients.
However, a Phase 3 randomized, double-blind, placebo-controlled trial is currently underway to validate its clinical benefits. This study focuses on individuals who carry the SOD1 genetic mutation but have not yet displayed symptoms of ALS. The trial aims to evaluate whether Qalsody can prevent the onset of ALS symptoms in these individuals and will compare the proportion of participants who develop symptoms between those who receive Qalsody and those who receive a placebo.
The FDA’s approval of Qalsody for the treatment of SOD1-ALS marks a significant development for patients with this subtype of ALS. While the drug’s effectiveness was evaluated on a surrogate endpoint, the observed reductions in plasma NfL concentration are reasonably likely to predict a clinical benefit to patients. The ongoing Phase 3 trial will provide further insights into Qalsody’s clinical benefit in individuals who are carriers of the SOD1 genetic mutation and do not yet have symptoms. Healthcare professionals experienced in performing lumbar punctures will administer Qalsody intrathecally.