Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co-Expression Patterns: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

OBJECTIVE: Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE). METHODS: During screening, patients with active, non-organ-threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed). Patients with improved disease activity were randomized 1:1 to obexelimab 5 mg/kg intravenously or placebo once every 2 weeks until week 32 or loss of improvement (LOI). RESULTS: In this study, 104 patients were randomized. Analysis of the primary endpoint, proportion of patients reaching week 32 without LOI, used an efficacy-evaluable (EE) population defined as patients who completed the study or withdrew for flare or treatment-related toxicity. This endpoint did not reach statistical significance: 21 of 50 obexelimab-treated patients (42.0%) versus 12 of 42 patients (28.6%) treated with a placebo (P = 0.183). Time to LOI was increased in obexelimab-treated patients versus patients treated with a placebo in the EE (hazard ratio [HR] 0.53, P = 0.025) and intention-to-treat (HR 0.59, P = 0.062) populations. In obexelimab-treated patients, B cells decreased approximately 50%, and trough concentration and inclusion in baseline gene expression clusters with high B cell pathway modules were associated with increased time to LOI. Obexelimab was associated with infusion reactions but was generally safe and well-tolerated. CONCLUSION: Although the primary endpoint was not reached, secondary analysis showed time to LOI was significantly increased in obexelimab-treated patients, and analysis of patient subsets defined by gene expression patterns at baseline suggests a responding subpopulation.

A prospective, randomized, double-blind, multicentre, parallel-group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients with rheumatoid arthritis.

AIM: In this study, efficacy, tolerability and safety of biosimilar adalimumab (Exemptia; Zydus Cadila) was compared with reference adalimumab (Humira; AbbVie) in patients with moderate to severe rheumatoid arthritis (RA). METHOD: In this multicentre, prospective, randomized, double-blind, active controlled parallel arm study, 120 patients with moderate to severe RA were given 40 mg of either test adalimumab (Exemptia) or reference adalimumab (Humira) by subcutaneous route every other week for 12 weeks. The primary endpoint was proportion of responders in two tretament groups by American College of Rheumatology 20 (ACR20) at week 12. The secondary endpoints were change in Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and proportion of patients with an ACR50 and ACR70 response in two treatment groups at week 12. Safety outcomes were also assessed. RESULTS: After 12 weeks, patients treated every other week with test adalimumab (Zydus Cadila) had statistically similar response rates as compared to reference adalimumab (AbbVie): ACR20 (82% vs. 79.2%; P > 0.7); ACR50 (46%, vs. 43.4%; P > 0.7); ACR70 (14% vs. 15.1%; P > 0.8). The change in DAS28-CRP score was -2.1 ± 1.09 and -2.1 ± 1.21, in test and reference products, respectively. It was statistically significant compared to baseline, but not significantly different between the two products. Three serious adverse events and no death was reported during the study. Both adalimumab preparations were safe and well tolerated in this study. CONCLUSION: The results demonstrated biosimilarity with respect to efficacy, tolerability and safety of test adalimumab (Exemptia) and reference adalimumab (Humira) in patients with moderate to severe RA.

A randomized placebo-controlled trial of the efficacy of denosumab in Indian postmenopausal women with osteoporosis.

INTRODUCTION: Osteoporosis is a serious condition affecting up to 50% of Indian postmenopausal women. Denosumab reduces bone resorption by targeting the receptor activator of nuclear factor-κB ligand. This study assessed the efficacy and safety of denosumab in Indian postmenopausal women with osteoporosis. MATERIALS AND METHODS: In this double-blind, multicenter, phase 3 study, 250 Indian postmenopausal women aged 55 to 75 years (T-score <-2.5 and >-4.0 at the lumbar spine or total hip; serum 25(OH) D levels ≥20 ng/mL) were randomized to receive one subcutaneous dose of denosumab 60 mg or placebo. All subjects received oral calcium ≥1000 mg and vitamin D3 ≥ 400 IU daily. The primary end point was mean percent change in bone mineral density (BMD) at the lumbar spine from baseline to Month 6. Secondary end points included mean percent change from baseline in BMD at total hip, femoral neck, and trochanter at Month 6 and median percent change from baseline in bone turnover markers at Months 1, 3, and 6. RESULTS: Total 225 subjects (denosumab = 111, placebo = 114) completed the six-month study. Baseline demographics were similar between groups. A 3.1% (95% confidence interval, 1.9%, 4.2%) increase favoring denosumab versus placebo was seen for the primary end point (P < 0.0001). Denosumab demonstrated a significant treatment benefit over placebo for the secondary end points. There were no fractures or withdrawals due to adverse events. CONCLUSIONS: Consistent with results from studies conducted in other parts of the world, denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a six-month period in Indian postmenopausal women.