Arimoclomol Shows Promise for Treating Rapidly Progressive SOD1 ALS

Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis
Due to the rarity of rapidly progressive SOD1 ALS, this study had a small sample size and may be limited in power.

Arimoclomol 200 mg 3 times daily for 12 months is safe and tolerable in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS), according to a double-blind, placebo-controlled trial published in Neurology.

Investigators randomly assigned patients with rapidly progressive SOD1-mutant ALS to either arimoclomol 200 mg 3 times daily (n=17) or matched placebo (n=19) for a total of 12 months. In-person evaluations occurred at baseline and at the second month of treatment; remote assessments were performed throughout the rest of the study period.

During the study, investigators examined neurologic function, slow vital capacity, vital signs, and blood and urine for safety outcomes. Additionally, the Revised ALS Functional Rating Scale (ALSFRS-R) and forced expiratory volume in 6 seconds were used to assess functional changes related to treatment. Tolerability and safety outcomes were the prime focus of this study; however, investigators also examined survival at 12-month follow-up.

No significant differences were observed between groups with regard to baseline characteristics. Adverse events were generally mild and occurred in ≥4 participants. Of the adverse events, none was considered related to arimoclomol. When investigators adjusted for participants’ baseline ALSFRS-R score and riluzole use, survival appeared to favor arimoclomol over placebo (hazard ratio 0.77; 95% CI, 0.32-1.80; P =.55).

A Cox proportional hazards model demonstrated similar survival findings (unadjusted hazard ratio 0.67; 95% CI, 0.29-1.48; P =.33). Declines in ALSFRS-R were slower in the arimoclomol- vs placebo-treated group (2.5 ± 0.4 points/month vs 3.0 ± 0.4 points/month, respectively; 95% CI, −0.63-1.63; P =.37).

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Because of the rarity of rapidly progressive SOD1 ALS, this study had a small sample size and may be limited in power. The investigators suggest that the lack of wet biomarker data was another limitation for this analysis.

Further research on higher arimoclomol doses may help “broaden the eligibility criteria to include a more diverse population of patients with ALS, since arimoclomol’s mechanism of action is likely to be relevant to all forms of ALS, in which aberrant proteostasis plays an essential role in disease pathophysiology.”


Benatar M, Wuu J, Andersen PM, et al. Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS. Neurology. 2018;90:e565-e574.