Qalsody, a Novel Therapy for Familial SOD1-ALS

Peggy Merriman RN, BSN, Director of Care Services, ALS United Illinois

The first genetic mutation discovered as a cause of familial ALS was in the superoxide dismutase 1 (SOD1) gene. The SOD1 gene carries the code for an enzyme that plays an important role in protecting cells from harmful waste products by neutralizing them at a cellular level. Mutations in this gene cause the protective SOD1 protein to malfunction. Five to ten percent of all cases of ALS are familial, and of those familial cases, 10 – 20% are carriers of a SOD1 mutation. In addition, a very small percentage (1-2%) of sporadic cases of ALS are found to be carriers of a SOD1 mutation. In April of 2023, the FDA granted accelerated approval of Qalsody™ (tofersen), which targets the malfunctioning SOD1 protein and is approved for adults who have ALS with a mutation in the SOD1 gene.

Over the 28 weeks of the double-blind VALOR study submitted for approval, participants who received the drug experienced a slightly slower rate of decline in their ALS symptoms, but this was not statistically significant. When researchers analyzed data from the open-label study in which all participants received active drug, the trend was toward further slowing disease progression rate over time. This may indicate that longer exposure to the drug improves the response, but it is too soon to tell this definitively. Researchers and the FDA will closely monitor the results of ongoing studies, including a study of people who carry the SOD1 gene but do not display symptoms.

Most researchers agree that current measures of strength and function in ALS, which presents and progresses differently in every patient, are not necessarily the most reliable measure of disease progression or of a drug’s effectiveness. The FDA has asked drug developers to assess and report more objective, measurable data such as biomarkers when investigating potential therapies. The Qalsody VALOR study measured levels of neurofilament light chain (NfL), a protein that is specific to nerve cells and detectable in blood and spinal fluid when there is injury or disease affecting nerve cell axons. NfL elevations are not specific to ALS and can be seen in a variety of neurologic diseases such as multiple sclerosis and Alzheimer’s disease. Higher levels of NfL correlate with more serious disease, and decreases in the levels are understood to be evidence of a drug’s effectiveness in reducing damage to nerve cells. In the VALOR study, those treated with Qalsody experienced a 55% reduction of their NfL blood levels, while those receiving placebo showed a 12% increase. It was this evidence that prompted the FDA to issue the accelerated approval of Qalsody.

Qalsody is administered monthly by a physician via lumbar puncture into the fluid space around the spinal cord. The treatment is not without serious potential complications, including increased intracranial pressure, inflammation of the spinal cord, and inflammation of the linings of the spinal cord and brain causing fever, severe headache, and nausea. The most commonly reported side effects (seen in ≥ 10% of patients in the study) were joint and muscle pain, fatigue, and increased white blood cell count in the spinal fluid. The cost of the drug is set at $14,230 per dose, and will be billed under Medicare Part B due to the need for administration in an outpatient setting.