ALS is characterized by progressive muscle weakness, atrophy, muscle twitching, stiffness, and eventually dysphagia and respiratory failure; Qalsody, approved in 2023, is an antisense oligonucleotide drug that reduces pathogenic proteins by degrading SOD1 mRNA, and is used to treat ALS with SOD1 gene mutations. Here is one of the most concerned questions, how effective is it in treating ALS?
How effective is Qalsody in treating ALS?
Trial of Qalsody for treating ALS
The efficacy of Qalsody was evaluated in a 28-week randomized, double-blind, placebo-controlled clinical study led by Dr. Timothy M Miller, in patients aged 23 to 78 years with weakness caused by ALS and SOD1 mutations confirmed by central laboratories (NCT02623699). A total of 108 patients were enrolled in the trial, who were randomly divided into groups of 2:1 to receive Qalsody or placebo. The primary endpoint was the change from baseline to week 28 in the total score of the ALS Functional Rating Scale-Revised (ALSFRS-R; range 0 to 48, with higher scores indicating better function) in participants predicted to have faster disease progression. Secondary endpoints included changes in total concentrations of SOD1 protein in cerebrospinal fluid (CSF), concentrations of neurofilament light chain in plasma, slow mobility, and handheld dynamometers of 16 muscles. The trial results showed that:
Qalsody resulted in greater reductions in concentrations of SOD1 in cerebrospinal fluid and neurofilament light chain in plasma compared with placebo. In the subgroup with faster progression (primary analysis), by week 28, the change in ALSFRS-R score was -6.98 for Qalsody and -8.14 for placebo. The results of the secondary clinical endpoints were not significantly different between the two groups.
Screenshot of the efficacy results of the Qalsody instruction manual trial for the treatment of ALS on the US FDA official website
The above results show that in patients with SOD1 ALS, Qalsody reduced the concentration of SOD1 in cerebrospinal fluid and the concentration of neurofilament light chain in plasma within 28 weeks, and the treatment of the disease is effective.
Dr. Timothy M Miller Co-director of the ALS Center Director of Miller Laboratory David Clayson Professor of Neurology
Dr. Miller, the initiator of the experiment, once said: "For other ALS drug development projects, if they can also reduce the level of neurofilament protein light chain like Qalsody, it can speed up the time to determine whether the drug is effective or its ability to slow the progression of neurodegenerative diseases."
