OP0325 SAFETY AND EFFICACY OF LENABASUM IN AN OPEN-LABEL EXTENSION OF A PHASE 2 STUDY IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS SUBJECTS (DCSSC)
Authors: Robert Spiera, Laura Hummers, Lorinda Chung, Tracy Frech, Robin Domsic, Vivian Hsu, Daniel Furst, Jessica Gordon, Maureen Mayes, Robert Simms, Elizabeth Lee, Scott Constantine, Nancy Dgetluck, Barbara White
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Lenabasum is a synthetic, non-immunosuppressive, selective cannabinoid receptor type 2 agonist that activates resolution of innate immune responses and limits fibrosis in animal models of SSc. Lenabasum had acceptable safety and tolerability, and improved efficacy outcomes in the 16-week, double-blinded, randomized, placebo-controlled Part A of Phase 2 trial JBT101-SSc-001 (NCT02465437) in dcSSc subjects. <h3>Objectives</h3> To provide long-term open-label safety and efficacy data in dcSSc subjects in study JBT101-SSc-001. <h3>Methods</h3> Subjects who completed Part A were eligible to receive oral lenabasum 20 mg BID in an open-label extension (OLE) that assessed safety and efficacy at 4 weeks, then every 8 weeks. <h3>Results</h3> 36/38 (95%) eligible subjects enrolled in the OLE, with mean interval of 134 (range 33-392) days or 19.1 weeks from end of dosing in Part A to start of OLE when subjects received only standard-of care drugs. 34/36 (94%) subjects were on stable doses of immunosuppressive drugs. At safety data cut-off, 31 (86%) subjects finished 1 year, 30 (83%) finished 18 months, and 24 finished ≥ 2 years in the OLE. Thirty-five (97%) subjects experienced at least 1 AE; 239 AEs have occurred during the OLE to date. Seven (19%) subjects had ≥ 1 AE considered related to lenabasum in the OLE. Only fatigue (1 subject) was considered definitely-related, none of the related AEs were serious or severe. Most subjects experienced AEs that were mild (n = 6, 17%) to moderate (n = 24, 67%) in maximum severity. Four (11%) had severe AEs and 1 (3%) had a life-threating AE of renal crisis caused by high-dose steroids. AEs in ≥ 10% of subjects: upper respiratory tract infection (n = 11, 31%), skin ulcer and arthralgia (each n = 6, 17%), urinary tract infection (n = 5, 14%), and diarrhea, nasopharyngitis, and cough (each n = 4, 11%). Dizziness and fatigue occurred in 3 (8.3%) subjects each. At the time of efficacy data cut-off, 30/36 (83%) subjects had completed ≥ 18 months in the OLE. Improvement was seen in multiple physician- and patient-reported efficacy outcomes; selected outcomes are shown in Figure 1 Compared to Baseline at study start, the CRISS median score (primary efficacy outcome) was 0.99 (0.43 IQR) at Week 76 and mRSS declined by mean (SD) = -10.7 (7.2) points. HAQ-DI, Physician Global Assessment, Patient Global Assessment, skin symptoms, itch, and multiple PROMIS-29 domains also improved. FVC% predicted was relatively stable during the OLE; mean (SD) FVC% predicted decreased by 2.5% from study start. <h3>Conclusion</h3> Lenabasum continues to have a favorable safety and tolerability profile in the OLE of Phase 2 trial JBT101-SSc-001 with no lenabasum-related serious AEs or study discontinuations. Only 7 (19%) subjects had an AE related to lenabasum in ≥ 18 months of OLE dosing. ACR CRISS score, mRSS, Physician Global Assessment, and multiple patient-reported outcomes show continued improvement, although background therapy, potential for spontaneous improvement, and open-label dosing limit what can be definitely attributed to lenabasum. <h3><b>Disclosure of Interests:</b>&nbsp;</h3> Robert Spiera Grant/research support from: Roche-Genentech, GlaxoSmithKline, Bristol-Myers Squibb, Boehringer Ingelheim, Cytori, Chemocentryx, Corbux, Consultant for: Roche-Genentech, GlaxoSmithKline, CSL Behring, Sanofi Aventis, Laura Hummers Grant/research support from: Site PI for phase 2 and 3 clinical trials (Cumberland, Glaxo Smith Kline, Boerhinger Ingleheim, Corbus, Cytori), Consultant for: CSL Behring, Lorinda Chung Grant/research support from: United Therapeutics, Consultant for: Reata, Bristol Meyers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos, Tracy Frech: None declared, Robin Domsic Consultant for: Eicos Sciences Inc/Civi Biopharma and Boehringer-Ingelheim., Vivian Hsu: None declared, Daniel Furst Grant/research support from: F. Hoffmann-La Roche, Genentech, Jessica Gordon Grant/research support from: Corbus Pharmaceuticals Cumberland Pharmaceuticals, Maureen Mayes Grant/research support from: Maureen Mayes is a clinical trial investigator for Boehringer-Ingelheim; Galapagos, Reata, Sanofi, Merck-Serono, Consultant for: Maureen Mayes is a member of scientific advisory boards for Galapagos NV (Pharma), Boehringer-Ingelheim, Mitsubishi-Tanabe, Astellas: Grant Review Board for Actelion., Speakers bureau: Maureen Mayes received personal fees for being a conference speaker on the use of autoantibodies in connective tissue diseases for Medtelligence, Robert Simms: None declared, Elizabeth Lee Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc., Scott Constantine Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc., Nancy Dgetluck Employee of: Corbus Pharmaceuticals, Inc., Barbara White Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc.