Tofersen (Qalsody)

Amyotrophic lateral sclerosis (ALS) is a debilitating disease caused by degeneration of cortical, brainstem, and spinal cord motor neurons and, in some cases, frontotemporal cortical neurons. The neurodegeneration results in progressive muscle weakness, muscle spasticity, dysarthria, dysphagia, cognitive and behavioral impairments, and other motor symptoms. The exact etiology of ALS is unclear but is likely due to multiple genetic (e.g., C9orf72, TARDBP, SOD1, FUS genes) and environmental factors. The superoxide dismutase 1 (SOD1) gene mutation affects approximately 2% of ALS cases, which equates to about 500 patients in the United States. Onset typically occurs at age 50 to 75 years and is more frequently reported in males than females, with a lifetime risk of about 0.29% and 0.25%, respectively. Unfortunately, prognosis is poor with a median survival of 2 to 4 years, and respiratory insufficiency is the most common cause of death. Patients presenting with suspected ALS are typically evaluated using the revised El Escorial/Arlie House criteria, which utilize clinical and electrophysiologic evaluations to ensure all the hallmark signs and symptoms are present while ruling out other neurodegenerative diseases. Once diagnosed, therapeutic options include riluzole (Rilutek tablets, Tiglutik suspension, and Exservan oral film) 50 mg orally twice daily, which modulates the actions of glutamate to slow disease progression, edaravone (Radicava oral suspension), a free radical scavenger and antioxidant, as concomitant therapy or as monotherapy if the patient is intolerant to riluzole, and sodium phenylbutyrate-taurursodiol (Relyvrio) as monotherapy or in combination with any of the aforementioned agents. Tofersen (Qalsody) is an antisense oligonucleotide indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain observed in pati ents treated with tofersen (Qalsody). Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial. Amyotrophic lateral sclerosis (ALS) is a debilitating disease caused by degeneration of cortical, brainstem, and spinal cord motor neurons and, in some cases, frontotemporal cortical neurons. The neurodegeneration results in progressive muscle weakness, muscle spasticity, dysarthria, dysphagia, cognitive and behavioral impairments, and other motor symptoms. <a id="