Nabiximols Efficacy in MS Spasticity: Treatment Effects on Spasticity Numeric Rating Scale Score and Muscle Spasm Frequency in 2 Randomized Clinical Trials

Background: Nabiximols improved spasticity in people with multiple sclerosis (PwMS) in 2 RCTs with enrichment design.

Objectives: To evaluate the treatment effect of nabiximols during each week of the double-blind, placebo-controlled portion of GWSP0604 and SAVANT using an equivalent statistical model.

Methods: Both trials used a 4-week single-blind lead-in Part A to identify initial responders. Participants were randomized in Part B to nabiximols or placebo immediately after Part A in GWSP0604 and after a 4-week washout period in SAVANT. Participants reported Spasticity numeric rating scale (NRS) score (0–10) and spasm frequency daily. Mean 7-day average daily Spasticity NRS score and mean 28-day average daily spasm frequency were assessed. The treatment effect measured as change from Part B baseline in Spasticity NRS score and average daily spasm count was assessed throughout the 12-week Part B treatment period. Incidence of AEs was assessed during Parts A and B.

Results: At Part A baseline, mean Spasticity NRS scores were similar for the Part B randomized groups (6.9 to 7.0) (SAVANT [n=106] and GWSP0604 [n=241]). In SAVANT, after the washout period, Part B baseline mean Spasticity NRS scores were 6.9 for the nabiximols and placebo groups. In GWSP0604, Part B baseline mean Spasticity NRS scores were 3.9 for both groups. In both studies, the difference in Spasticity NRS scores favored nabiximols. This effect was significant at all 1-week time points through week 12: ‑0.52 to ‑1.97 for SAVANT (all p<0.003 and ‑0.36 to ‑0.85 for GWSP0604 [all p<0.007]). Similarly, nabiximols reduced spasm frequency versus placebo at all time points and for all baseline spasm frequency thresholds assessed across the 2 studies: treatment difference of 11% to 37% (all p<0.05). The safety profile of nabiximols was consistent with previous studies.

Conclusions: Nabiximols showed significant and sustained treatment effect on Spasticity NRS score and spasm frequency in PwMS and was generally well tolerated.