These post hoc analyses assessed the safety profile of nabiximols in responders (≥20%) vs nonresponders during Phase A (4 weeks) and efficacy outcomes for nabiximols vs placebo during Phase B (12 weeks) relative to Phase A baseline (instead of Phase B baseline).

In the phase 3 trial (NCT00681538) responders in single-blind Phase A were randomized to nabiximols or placebo in double-blind Phase B. Nabiximols improved spasticity vs placebo in the prespecified primary analysis.

Assessments included AE incidence, percent change in NRS spasticity score, daily spasm frequency, and proportion of caregivers reporting improvement in participants functional abilities on a Caregiver Global Impression of Change (CGIC) scale.

Of 572 PwMS enrolled, 266 were responders at the end of Phase A with 241 randomized to nabiximols (n=124) or placebo (n=117) in Phase B. During Phase A, 40% of responders and 53% of nonresponders had an AE; AE profiles were similar between groups, except dizziness, which occurred more frequently in nonresponders vs responders (18% vs 10%). During Phase B, 53% of PwMS on nabiximols reported ≥1 AE vs 49% on placebo; 8 PwMS on nabiximols discontinued due to an AE vs none on placebo. Phase B randomized cohorts had similar mean percent reductions in spasticity NRS and spasm frequency during Phase A. At the end of Phase B, mean percent decrease from Phase A baseline (nabiximols vs placebo) was 46% vs 33% (P=0.011) in spasticity NRS; and in spasm frequency, 44% vs 24%  (P=0.006). Improvement from Phase A baseline on the CGIC scale was reported for 68% of PwMS on nabiximols vs 43% on placebo at end of Phase B.

Nabiximols was well tolerated and provided continued benefit to PwMS who remained on therapy in Phase B, with a variable loss of efficacy in PwMS who were randomized to placebo in Phase B.