FRI0470 A phase 2 study of safety and efficacy of lenabasum (JBT-101), a cannabinoid receptor type 2 agonist, in refractory skin-predominant dermatomyositis

Abstract

BackgroundEffective treatment options are limited for refractory skin disease in dermatomyositis (DM). Lenabasum is a non-immunosuppressive, synthetic, oral preferential CB2 agonist that triggers resolution of innate immune responses and reduces cytokine production by PBMC from DM patients.ObjectivesThe purpose of this study was to test safety and efficacy of lenabasum (aka JBT-101, anabasum) in DM subjects with refractory, moderate-to-severely active skin disease.MethodsA double-blind, randomised placebo-controlled 16 week Phase 2 trial (JBT101-DM-001; NCT02466243) enrolled adults with documented DM and a Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score ≥14, minimal active muscle involvement and failure or intolerance to hydroxychloroquine and stable DM medications including immunosuppressants. Subjects received 2 escalating dose levels of lenabasum (20 mg QD X 4 weeks, then 20 mg BID X 8 weeks) or PBO X 12 weeks. Subjects were followed off study drug X 4 weeks. Safety and efficacy outcomes were assessed from Day 1 through end of study at Week 16. The primary efficacy objective was to assess efficacy of lenabasum using CDASI activity score.Results11 adults each received lenabasum and PBO (n=22). Demographic and disease characteristics were similar in both cohorts. Both cohorts had mean CDASI activity scores in the severe range33–35 despite immunosuppressants (19/22 subjects). Lenabasum subjects had clinically meaningful improvement in CDASI activity scores with mean reduction ≥5 points at all visits after 4 weeks. Improvement had statistical significance at end of study (figure 1, p=0.02, 2-sided MMRM) that first became apparent after 4 weeks. Lenabasum provided greater improvement than placebo in CDASI damage index, patient-reported global skin disease and overall disease assessments, skin symptoms including photosensitivity and itch, fatigue, sleep, pain interference with activities, pain, and physical function (examples in figure 1). Improvements in secondary efficacy outcomes reached statistical significance (p≤0.1, 1-sided MMRM) at multiple visits after week 4 (figure 1). There were no serious, severe or unexpected adverse events (AEs) related to lenabasum. Tolerability of lenabasum was excellent with no study drop-outs. Subjects in the lenabasum cohort had numerically more mild AEs than placebo subjects (29 vs. 19) and fewer moderate AEs (4 vs. 7). AEs in ≥3 subjects in any cohort were diarrhoea, dizziness (lightheadedness), fatigue and dry mouth.Abstract FRI0470 – Figure 1Effects of Lenabasum on Efficacy Outcomes in Refractory, Skin-Predominant DMConclusionsLenabasum demonstrated consistent evidence of clinical benefit across multiple efficacy outcomes and had acceptable safety and tolerability in this Phase 2 trial in refractory skin disease in DM. Further evaluation of lenabasum in the treatment of DM is warranted.Disclosure of InterestV. Werth Consultant for: Corbus Pharmaceuticals, Inc., E. Hejazi: None declared, S. Pena: None declared, J. Haber: None declared, J. Okawa:...

239th ENMC International Workshop: Classification of dermatomyositis, Amsterdam, the Netherlands, 14–16 December 2018

“…The CDASI was used as a primary outcome for a phase 2 double-blind placebo-controlled trial of a nonpsychoactive cannabinoid, lenabasum [139] . It was able to demonstrate significant improvement in the skin in a short trial that has now led to a phase 3 global trial.…”

The pruritogenic role of the type 2 immune response in diseases associated with chronic itch

“…45 While the pathogenesis of DM is not completely understood, two studies suggest an increase in Th2-related cells compared to Th1-related cells in the peripheral blood of DM patients. 46,47 In a novel study on DM-associated pruri- 49 As a whole, given the high prevalence of pruritus in DM along with the significant association between the VAS itch scores with IL-31 and its respected receptors, DM-associated pruritus is likely in part driven by key cells and cytokines of Th2 immune response.…”

The Impact of Cannabinoid Receptor 2 Deficiency on Neutrophil Recruitment and Inflammation

“…Interestingly, these compounds were found not to provide meaningful analgesia despite the efficacy observed in pre-clinical models of pain management (Ostenfeld et al, 2011;Pereira et al, 2013). However, The CB2 agonist, lenabasum, successfully passed phase 2 trials in the context of dermatomyositis where the compound was observed to provide greater improvement in a dermatological damage index after four weeks of administration (Werth et al, 2018). Lenabasum is currently being used in a phase 3 clinical trial for patients with dermatomyositis with a completion date of September 2021 (Werth et al, 2019).…”