By Lucy Piper, medwireNews Reporter
medwireNews: Tetramethylpyrazine nitrone does not slow overall functional decline in patients with amyotrophic lateral sclerosis (ALS), but it may help retain grip strength and is well tolerated, suggest study findings.
Dongsheng Fan (Peking University Third Hospital, Beijing, China) and colleagues found no significant difference in the decline of the ALS Functional Rating Scale–Revised (ALSFRS-R) score – the primary endpoint of the study – after 180 days among 96 patients with ALS who were randomly assigned to receive tetramethylpyrazine nitrone compared with 52 assigned to receive placebo.
The ALSFRS-R score, which ranges from 0 to 48 points with a low score indicating worse function, fell from an average 41.8 points at baseline by a least squares mean (LSM) of 8.36 points among 46 patients receiving low-dose tetramethylpyrazine nitrone (600 mg twice daily), 7.68 points among 52 patients receiving high-dose tetramethylpyrazine nitrone (1200 mg twice daily), and 7.47 points among 50 patients given placebo.
This translated to nonsignificant differences in ALSFRS-R score changes of 0.89 points and 0.20 points with low- and high-dose tetramethylpyrazine nitrone, respectively, versus placebo.
The phase 2 study participants (74% men) had a mean age of 55 years and were predominantly of Han Chinese ethnicity (98%). They had a mean ALS duration of 14.4 months and had experienced at least a 1–4-point decrease in ALSFRS-R score during a 3-month screening period preceding randomization.
“Despite not meeting the primary end point of ALSFRS-R change, tetramethylpyrazine nitrone significantly delayed grip strength deterioration, an important secondary end point and key marker of ALS disease progression and patients’ quality of life,” note the researchers in JAMA Network Open.
At day 180, the decline in grip strength (mean of both hands) was attenuated in patients taking tetramethylpyrazine nitrone, with LSM differences versus placebo of 1.06 kg with the low dose, a nonsignificant difference, and 2.46 kg with the high-drug dose, a significant difference. The respective LSM reductions from maximum baseline strengths of 14.5–16.5 kg were 6.53 kg and 5.14 kg with low- and high-dose tetramethylpyrazine nitrone, respectively, versus 7.60 kg from a baseline strength of 16.1 kg with placebo.
The effect of tetramethylpyrazine nitrone treatment on grip strength was particularly prominent in a subset of 90 patients younger than 65 years old whose ALSFRS-R score declined by 1–2 points during the screening period, designating them as having slow progression.
Among these patients, the LSM reduction in grip strength at 180 days was a nonsignificant 2.51 kg less in patients taking low-dose tetramethylpyrazine nitrone versus placebo and a significant 3.63 kg less in those taking high-dose tetramethylpyrazine nitrone.
This subgroup with slow progression also showed significant 180-day improvement in ALSFRS-R bulbar subdomain scores with high-dose tetramethylpyrazine nitrone versus placebo (LSM difference of 0.66 points) and in respiratory subdomain scores with both low and high doses of the drug (LSM differences of 0.54 and 0.61 points, respectively).
With regard to safety, Fan et al found adverse events (AEs) were similar across the three groups. Treatment-emergent AEs of grade 3 or more severe occurred in 10.0% of patients in the low-dose tetramethylpyrazine nitrone group, 5.8% of those in the high-dose tetramethylpyrazine nitrone group, and 5.9% of those in the placebo group. Treatment-related AEs occurred in a corresponding 24.0%, 34.6%, and 17.6%, and were “mostly mild or moderate in intensity,” say the team, with “no severe treatment-related adverse events or deaths.”
News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group
J Netw Open 2025; 8: e2461055