Background/Purpose: Anabasum (JBT-101) is a selective cannabinoid receptor type 2 agonist that activates resolution of innate immune responses and limits fibrosis in animal models of SSc.  It is a synthetic, oral, non-immunosuppressive small molecule.  Anabasum had acceptable safety and tolerability and showed evidence of clinical benefit in diffuse cutaneous SSc (dcSSc) in Phase 2 trial JBT101-SSc-001 (NCT02465437).  The objective of this study was to provide long-term open-label safety and efficacy data in dcSSc subjects who received anabasum in that trial.

Methods: Subjects who completed the double-blind placebo-controlled (DBPC) part of JBT101-SSc-001 were eligible to receive anabasum 20 mg BID in an open-label extension (OLE).

Results: 36/38 (95%) eligible subjects enrolled in the OLE and 34/36 (94%) were on baseline immunosuppressive drugs.  At the time of data cut-off, 1 subject had discontinued from the OLE, the duration of OLE dosing was median 194 days (range 25, 207 days) and total duration of DBPC + OLE dosing with anabasum was median 234 days (range 28, 295 days).  All 36 subjects had at least one OLE visit ≥ 28 days post baseline.  Adverse events (AEs, n = 88) occurred in 28/36 (78%) subjects in the OLE.  Most AEs were mild (55/88, 62%) or moderate (30/88, 34%) in severity and unrelated to anabasum (75/88, 85%).  The AEs that occurred in ≥ 10% of subjects (n, % of subjects) were mild fatigue (5, 14%) and mild/moderate upper respiratory tract infection (4, 11%).  Dizziness occurred in 2 (6%) subjects.  Only one subject had more than mild or moderate AEs.  That subject developed renal crisis 7 days after starting 60 mg/day prednisone prescribed by a non-study physician for suspected temporal arteritis and had 2 severe and 1 life-threatening/serious AEs related to the renal crisis and deemed unrelated to anabasum.  In the period between DBPC and OLE off study product (median 50 days, range 5 – 360 days), the modified Rodnan skin score (mRSS) was stable in all subjects, subjects treated with anabasum and subjects treated with placebo during DBPC dosing (Table 1).  After 10 weeks of anabasum treatment in OLE (Visit 3 in OLE), mRSS declined from baseline in these same groups of subjects.

Table 1. Changes in mRSS before and after 10 weeks dosing in OLE

Conclusion: In OLE of Phase 2 trial JBT101-SSc-001, anabasum continues to have acceptable safety and tolerability in dcSSc with no severe or serious AEs or study discontinuations related to anabasum.  The mRSS improved, although open-label nature of dosing with anabasum is acknowledged.  These data support further testing of anabasum for treatment of dcSSc.