Post Hoc Analysis of Nabiximols Efficacy By Concomitant Medication Use in 2 Enriched Placebo-Controlled Randomized Clinical Trials (RCTs)

Background: Spasticity, a common symptom of multiple sclerosis (MS), is undertreated, and standard treatment options often fail to provide adequate control. Nabiximols oromucosal spray, a complex botanical mixture containing delta-9-tetrahydrocannabinol and cannabidiol as the principal cannabinoids as well as non-cannabinoid components, improved spasticity in people with MS (PwMS) measured by a spasticity 0–10 numeric rating scale (NRS) in 2 placebo-controlled RCTs, SAVANT and GWSP0604.

Objectives: To assess treatment outcomes for PwMS spasticity taking nabiximols with or without concomitant anti-spasticity medications (ASMs), such as baclofen.

Methods: SAVANT and GWSP0604 used a single-blind lead-in Part A followed by randomization of eligible participants in Part B. In SAVANT only, patients were allowed to optimize the dose of their ASM(s). Participants reported Spasticity NRS score 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 by concomitant ASM was evaluated. Incidence of AEs was assessed.

Results: In SAVANT, 53 participants were randomized to placebo (89% on baclofen) and 53 to nabiximols (81% on baclofen). In GWSP0604, 117 participants were randomized to placebo (63% on baclofen) and 124 to nabiximols (53% on baclofen). In both studies, improvement in Spasticity NRS scores and reduction in spasm frequency significantly favored nabiximols versus placebo in the overall population. Improvement in Spasticity NRS scores or decreased spasm frequency was unaffected by baclofen use, with no evidence of a difference between the treatment effects in each group (p=0.8204 and p=0.4412 in SAVANT; p=0.6192 and p=0.1792 in GWSP0604). In GWSP0604, no significant difference between treatment effects in groups was observed when the number of ASMs was evaluated (0, 1, 2+). The safety profile of nabiximols was manageable and consistent with the known safety profile of the approved medication in the European Union.

Conclusions: Nabiximols showed significant and sustained treatment effect on Spasticity NRS score and spasm frequency in PwMS regardless of use of concomitant ASMs, such as baclofen.