AbbVie announced positive data from a Phase 2 study of ABBV-3373, an investigational anti-tumor necrosis factor (TNF) Glucocorticoid Receptor Modulator (GRM) steroid antibody drug conjugate (ADC), in adult patients with moderate to severe rheumatoid arthritis. Data confirmed the clinical activity of ABBV-3373 and support advancing the development of the platform in rheumatoid arthritis and initiating clinical studies in other immune-mediated diseases.
The phase 2, multicenter, randomized, double-blind, double-dummy, active-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of ABBV-3373 in adult patients with moderate to severe rheumatoid arthritis with an inadequate response to MTX. Patients were randomized in a 2:1 ratio to ABBV-3373 (n=31) at 100 mg, every other week (EOW) or adalimumab (n=17) at 80 mg, EOW for 12 weeks. The primary endpoint was the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) from baseline to week 12 and two statistical comparisons were pre-specified. The first compared ABBV-3373 and mean outcome from historical adalimumab data. The second compared ABBV-3373 and combined in-trial and historical adalimumab data. Results of the first comparison show a greater difference in the primary endpoint change in DAS28-CRP from baseline to week 12 for ABBV-3373 (-2.65) as compared to a pre-specified historical adalimumab mean (-2.13). Results of the second comparison, based on a Bayesian analysis, predicted with a 90 percent probability that ABBV-3373 was associated with a greater improvement on DAS28-CRP from baseline to week 12 than adalimumab based on in-trial data combined with historical data. Additionally, evaluations of serum cortisol levels over 12 weeks indicate that ABBV-3373 showed no systemic glucocorticoid effects.
Full results from this study will be presented at an upcoming medical meeting and/or published in a peer-reviewed publication.
ABBV-3373 is an ADC comprised of a novel glucocorticoid receptor modulator (GRM) linked to adalimumab, and aims at modulating TNF-mediated inflammatory pathways by delivering a glucocorticoid payload directly into activated immune cells expressing membrane bound TNF. This ADC was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side-effects associated with glucocorticoids.