SAFETY AND EFFICACY OF LENABASUM IN SUBJECTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS SUBJECTS: AN OPEN-LABEL EXTENSION OF A PHASE 2 STUDY
Objectives:
1. Identify the impact of systemic sclerosis on the patient.
2. Describe the effects of lenabasum in patients with diffuse cutaneous systemic sclerosis.
Introduction:
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 a 16-week, double-blind, randomized, placebo-controlled Phase 2 study in dcSSc subjects (NCT02465437).
The purpose of this open-label extension (OLE) phase was to provide long-term safety and efficacy data on lenabasum.
Subjects who completed the double-blind phase were eligible to receive oral lenabasum 20 mg BID in the OLE that assessed safety and efficacy at 4 weeks, then every 8 weeks.
Case Description:
In the OLE, 36/38 (95%) eligible subjects enrolled, and 29 (81%) completed at least Week 108. Four subjects withdrew consent, 2 withdrew due to AEs unrelated to lenabasum (tendonitis and scleroderma renal crisis), and 1 withdrew for other reasons. At Week 108, 35 (97%) subjects experienced 1 AE, with 294 total AEs. Seven (19%) subjects had ≥1 AE considered related to lenabasum in the OLE, and 3 had AEs judged to be probably or definitely related to lenabasum: 1 had mild fatigue, 1 had a moderate skin ulcer and moderate lymph node pain, and 1 had mild disturbance in attention and mild lethargy and moderate feeling abnormal. Most subjects experienced AEs that were of mild (n=6, 17%) or moderate (n=23, 64%) severity. Six (17%) had severe AEs, and 1 (3%) had a life-threating AE of renal crisis associated with high-dose steroids. AEs in ≥10% of subjects were upper respiratory tract infection (n=13, 36%); urinary tract infection, and arthralgia (each n=6, 17%); and skin ulcer (5, 13.9%). Anemia, cough, depression, dizziness, headache, and herpes zoster occurred in 4 (11.1%) subjects each. Improvement was seen in multiple physician- and patient-reported efficacy outcomes. The ACR CRISS median score (primary efficacy outcome) was 0.98 at Week 108 and mRSS declined by mean (SD) = -9.2 (7.2) points. Health Assessment Questionnaire-Disability Index, Physician Global Assessment, Patient Global Assessment, skin symptoms, itch, and multiple PROMIS-29 domains also improved. FVC% predicted decreased 2% from baseline.
Discussion:
In this OLE, lenabasum had a favorable safety and tolerability profile with no serious AEs or study discontinuations related to lenabasum. Efficacy outcomes showed stable improvement from about 1 year in the OLE. Background therapy, natural history of the disease, and open-label dosing limit what can be definitely attributed to lenabasum.