Phase 3 Trial Shows Ultrahigh-Dose Methylcobalamin Slows Progression of Early-Stage ALS

A twice-weekly intramuscular injection of ultrahigh-dose methylcobalamin appears to slow clinical progression in patients with early-stage amyotrophic lateral sclerosis (ALS), according to new research published in JAMA Neurology.

“The effectiveness of currently approved drugs for ALS is restricted; there is a need to develop further treatments,” researchers explained. “Initial studies have shown ultrahigh-dose methylcobalamin to be a promising agent.”

The phase 3 clinical trial included 130 patients in Japan within 1 year of ALS symptom onset. All participants had experienced a 1- to 2-point decrease on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score over 12 weeks of initial observation, indicating a moderate rate of disease progression.

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For the study, researchers randomly assigned 65 patients to intramuscular injection of 50-mg methylcobalamin and 65 patients to intramuscular injection with placebo. Injections were administered twice weekly over 4 months.

Average changes on ALSFRS-R total score at the 4-month mark were −2.66 with methylcobalamin and −4.63 with placebo, according to the study results. The 1.97-point difference between the treatment groups was significant. The incidence of adverse events did not differ between treatment groups.

“Results of this randomized clinical trial showed that ultrahigh-dose methylcobalamin was efficacious in slowing functional decline in patients with early-stage ALS and with moderate progression rate,” researchers concluded, “and was safe to use during the 16-week treatment period.”

Reference

Oki R, Izumi Y, Fujita K, et al. Efficacy and safety of ultrahigh-dose methylcobalamin in early-stage amyotrophic lateral sclerosis: a randomized clinical trial. JAMA Neurol. Published online May 9, 2022. doi: 10.1001/jamaneurol.2022.0901