ABBV-3373: A potential new therapeutic agent for RA

ABBV-3373 is a potential new drug for rheumatoid arthritis (RA) that has shown promising efficacy and safety results in a 24-week randomised, double-blind, double-dummy, proof-of-concept phase 2 trial [1]. This antibody-drug conjugate combines the working mechanisms of TNF inhibitor adalimumab and a glucocorticoid receptor modulator (GRM) to improve patient outcomes.

Glucocorticoids are highly effective in treating RA. However, the potential systemic side effects limit the long-term use of these drugs. ABBV-3373 is an antibody-drug conjugate consisting of adalimumab linked to a proprietary GRM, which is designed to use the favourable aspects of a TNF inhibitor and a glucocorticoid. GRMs can selectively induce a receptor conformation in a way that only activates a subset of downstream signalling pathways, thereby combining agonistic and antagonistic properties of glucocorticoids, depending on the tissue in which it is expressed. This targeted approach may potentially dampen systemic side effects  [2].

In the current trial, RA patients were randomised 2:1 to placebo (n=96) or one of the experimental conditions: in-trial adalimumab (n=17; 80 mg subcutaneous every other week) or ABBV-3373 (n=31; 100 mg intravenous every other week). Efficacy and safety data of ABBV-3373 were compared with data of 242 historical adalimumab recipients, in-trial adalimumab users, and placebo users. Primary endpoint was the change from baseline 28-joint Disease Activity Score based on C-reactive protein (DAS28–CRP) scores at week 12.

The results were presented by Dr Frank Buttgereit (Charité University Medicine, Germany) and demonstrated patient benefits of ABBV-3373 over historical adalimumab users and placebo, represented as mean change on DAS28–CRP scores after 12 weeks of treatment: -2.65  for ABBV-3373 versus -2.13  for historical adalimumab (P<0.05) and versus -0.91 for placebo (P<0.001). No significant difference between DAS28–CRP mean changes of ABBV-3373 and in-trial adalimumab users was observed (see Figure).

Figure: Change from baseline in DAS28–CRP at week 12 [1]



DAS28–CRP, 28-joint disease activity score based on C-reactive protein.

** P<0.05; **** P<0.001

Similar positive results were obtained for secondary outcome measures: DAS28 based on Erythrocyte Sedimentation Rate, Crohn’s Disease Activity Index (CDAI), Simplified Disease Activity Index for RA (SDAI), ACR responses 20/50/70, and Health Assessment Questionnaire–Disability Index (HAQ–DI). Fewer AEs were reported in patients treated with ABBV-3373 (11, 35.5%) compared with in-trial adalimumab recipients (12, 70.6%). Nonetheless, 4 AEs in the ABBV-3373 population were considered serious: non-cardiac chest pain, pneumonia, upper respiratory tract infection, and anaphylactic shock (all n=1). Serious AEs were not reported in the in-trial adalimumab population. The safety profile of ABBV-3373 was fairly similar to that of adalimumab.

Dr Buttgereit argued that these findings demonstrate the potential of ABBV-3373 to provide benefits for RA patients compared with adalimumab. “All RA patients could benefit from the targeted delivery of this TNF inhibitor linked to a GRM”.

1. Buttgereit F, et al. Efficacy and Safety of ABBV-3373, a Novel Anti-TNF Glucocorticoid Receptor Modulator Antibody Drug Conjugate, in Patients with Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy: A Phase 2a Proof of Concept Study. OP0115, EULAR 2021 Virtual Congress, 2–5 June.
2. Meijer OC, et al. Ann Endocrinol (Paris). 2018;79(3):107-11.

 

Copyright ©2021 Medicom Medical Publishers



Posted on 2 August 202127 March 2024