Efficacy, Safety, Pharmacokinetics, and Immunogenicity of ABBV-154 in Adults With Glucocorticoid-Dependent Polymyalgia Rheumatica: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.
Academic Article
Overview
abstract
OBJECTIVE: An unmet need exists for glucocorticoid-sparing treatments for patients with polymyalgia rheumatica (PMR). The antibody-drug conjugate ABBV-154 comprises adalimumab conjugated to a glucocorticoid receptor modulator. We evaluated ABBV-154 versus placebo in patients with glucocorticoid-dependent PMR. METHODS: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, eligible patients had confirmed PMR, glucocorticoid response and two or more unequivocal PMR flares while tapering glucocorticoids and still on ≥5 mg daily prednisone equivalent. Randomized patients received subcutaneous placebo or ABBV-154 40, 150, or 340 mg once every other week. The primary efficacy endpoint was time to flare. The sponsor voluntarily terminated the study early. RESULTS: Overall, 181 patients were randomized (placebo, n = 50; ABBV-154: 40 mg, n = 42; 150 mg, n = 45; 340 mg, n = 44), and 67.4% completed study drug at week 24. Time to flare was longer for patients receiving ABBV-154 than those receiving placebo, with Kaplan-Meier estimate of 24-week flare-free rate being lower for placebo. The hazard ratios of ABBV-154 versus placebo were 0.49 (95% confidence interval [CI], 0.27-0.88), P = 0.017 for 40 mg; 0.44 (95% CI, 0.25-0.79), P = 0.006 for 150 mg; 0.20 (95% CI, 0.09-0.42), P < 0.001 for 340 mg. Incidences of treatment-emergent adverse events were similar between groups, and the most common across ABBV-154 cohorts was COVID-19 (16.0%). CONCLUSION: Treatment effects were observed for ABBV-154 cohorts compared with placebo for time to flare. ABBV-154 was generally well tolerated. Due to early study termination, results should be interpreted with caution.
