Obefazimod for Rheumatoid Arthritis

Obefazimod is an oral, first-in-class, small molecule that has demonstrated safety and profound anti-inflammatory activity in the completed Phase 2a and Phase 2b induction studies as well as in ongoing long-term maintenance studies in patients with moderate-to-severe ulcerative colitis (UC).

In addition to the clinical observations in UC patients, Abivax generated promising pre-clinical data from collagen-induced arthritis animal models that were the basis for moving into the Phase 2a clinical trial in rheumatoid arthritis (RA).

In June 2021, Abivax announced excellent top-line results of the induction phase of its Phase 2a clinical study of Obefazimod administered in combination with methotrexate (MTX) for the treatment of active moderate to severe RA. 60 patients who had either an inadequate response to methotrexate and/or TNFα inhibitors participated in the study.

The primary endpoint of this study, safety and tolerability, was met with 50mg once daily administration of obefazimod demonstrating a good safety and tolerability profile in the overall patient population during the 12-week induction phase.

Although the sample size of this study was not powered to show efficacy, the 50mg group already showed statistically significant differences for the key secondary endpoint ACR20 compared to placebo at week 12 in the Per Protocol population.

Patients who completed the induction study could roll over into a two-year open-label maintenance study to evaluate the long-term safety and efficacy of 50mg once daily oral administration of obefazimod in RA.
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Out of the 40 patients who enrolled into the Phase 2a maintenance study with obefazimod, 23 patients have reached the first year of treatment (as of February 28, 2022) and all achieved at least an ACR20, with 19 and 12 patients achieving ACR50 and ACR70 respectively.

57% of the patients (13/23) were in remission at week 52, assessed by the DAS28-CRP (< 2.6), corresponding to 33% (13/40) using the full analysis set (FAS).
All 23 patients (100%) who completed 52 weeks of treatment achieved at least an ACR20 response, which translates into 58% (23/40) in the FAS.
It is remarkable, that according to the observed cases population, 83% (19/23) and 52% (12/23) achieved even an ACR50 and ACR70 response respectively, corresponding to 48% (19/40) and 30% (12/40) according to the FAS.

Obefazimod was safe and the nature of the adverse events is consistent with what has been observed in more than 1,000 subjects who have so far been treated in other clinical trials with obefazimod across different indications. At present, some UC patients have been continuously treated for four years.

Based on the results of the Phase 2a clinical study, Abivax is planning to start a clinical phase 2b program in RA.