Efficacy, Safety, Pharmacokinetics, and Immunogenicity of ABBV-154 in Adults With Glucocorticoid-Dependent Polymyalgia Rheumatica: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.

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.