Antisense Oligonucleotide Tofersen Reduces SOD1 in SOD1 ALS

MONDAY, Oct. 3, 2022 (HealthDay News) -- The antisense oligonucleotide tofersen reduces the concentrations of superoxide dismutase 1 (SOD1) in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1, but it does not improve clinical end points, according to a study published in the Sept. 22 issue of the New England Journal of Medicine.

Timothy M. Miller, M.D., Ph.D., from the Washington University School of Medicine in St. Louis, and colleagues randomly assigned adults with SOD1 ALS to receive eight doses of tofersen or placebo over a 24-week period (72 and 36 patients, respectively; 39 and 21 predicted to have faster progression). The change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R) among patients predicted to have faster-progressing disease was the primary end point.

The researchers found that compared with placebo, tofersen led to greater reductions in concentrations of SOD1 in the cerebrospinal fluid and of neurofilament light chains in plasma. In the faster progression subgroup, there was no significant difference in the ALSFRS-R score change to week 28. Secondary clinical end points did not differ between the groups. Ninety-five patients entered an open-label extension; the change in ALSFRS-R score was −6.0 and −9.5 points in the early-start and delayed-start cohorts, respectively. For other end points, non-multiplicity-adjusted differences favoring early-start tofersen were seen.

"We see clear evidence that the drug slows down the initiating factor -- a SOD1 mutation -- as well as the neurodegenerative disease process," Miller said in a statement. "We didn't see substantial clinical improvement at six months, but the stabilization in function and strength at longer time points suggests it may take time for people to heal from the damage that has already been caused."

Several authors disclosed financial ties to biopharmaceutical companies, including Biogen, which manufactures tofersen and funded the study.

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