Background/Purpose: Lenabasum is a rationally-designed preferential cannabinoid receptor type 2 agonist that activates resolution of innate immune responses to reduce tissue inflammation and fibrotic processes. Lenabasum had acceptable safety and tolerability and improved efficacy outcomes in the initial 16-week double-blinded, randomized, placebo-controlled Part A of Phase 2 trial JBT101-DM-001 (NCT02466243) in classic or amyopathic dermatomyositis (DM) subjects with refractory skin disease and minimal or no active muscle involvement at the time of enrollment.

Methods: To provide long-term safety and efficacy data in DM subjects in study JBT101-DM-001, subjects who completed Part A were eligible to receive oral lenabasum 20 mg BID in an open-label extension (OLE) of that study that assessed safety and efficacy at 4 weeks, then every 8 weeks.

Results: 20/22 (91%) eligible subjects received lenabasum in the OLE.  Seventeen (85%) subjects were on stable baseline immunosuppressive drugs.  At the time of data cut-off, 18 (90%) subjects who enrolled in the OLE had entered the second year of the OLE, and all 18 had completed Week 68.

Twenty/20 (100%) of subjects experienced at least 1 AE, with 65 total AEs occurring among the subjects during the OLE to date.  The majority of AEs were mild (n = 16, 80%), and only 1 subject had an AE probably or definitely-related to lenabasum (mild fatigue).  Only 1 subject had a severe AE (fatigue) and that AE was considered unrelated to lenabasum.  AEs occurring in 3 (15%) subjects were dermatomyositis worsening (2 mild, 1 moderate), dizziness (all mild), fatigue (2 mild, 1 severe), nasopharyngitis (all mild). AEs occurring in 2 (10%) subjects were headache, herpes zoster, nausea, sinusitis, upper respiratory tract infection, and urinary tract infection – all were mild except 1 AE of sinusitis was moderate.  No serious AEs have been reported in this study to date.  

Improvement was seen in multiple physician- and patient-reported efficacy outcomes; selected outcomes are presented in Figure 1. Mean (SE) changes from study start at Week 68 in the OLE were: CDASI activity score = -21.8 (2.26), Patient Skin Activity VAS  = -3.0 (0.75); Skindex-29 Symptoms Domain  = -28.0 (SD); 5D Itch Score = -3.7 (SD); Physician Overall Disease VAS = -3.0 (SD); and Promis-29 Pain Interference = -4.5 (SD). Improvements were seen in other patient- and physician-reported efficacy outcomes. During the OLE, 2 subjects reduced mycophenolate, 2 were switched from methotrexate to mycophenolate, 1 started methotrexate, and 1 had a burst and taper of steroids.

Conclusion: To date, lenabasum treatment has been safe and well tolerated in the Phase 2 study JBT101-DM-001, with no serious AEs or study discontinuations related to lenabasum.  The CDASI activity score and multiple other physician and patient-reported outcomes improved, although limitations of attributing efficacy to lenabasum in the setting of open-label dosing is acknowledged.  These data support further testing of lenabasum for the treatment of DM, and a Phase 3 study of lenabasum in DM has started.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-lenabasum-at-week-68-in-an-open-label-extension-of-a-phase-2-study-of-lenabasum-in-refractory-skin-predominant-dermatomyositis-dm-subjects/