Obefazimod 50 mg for rheumatoid arthritis delivers in phase II trial

The investigational drug ABX464, also known as obefazimod, helps reduce disease activity in patients with rheumatoid arthritis (RA), according to the results of a phase II trial. The 50-mg dose is well tolerated, while the higher dose is associated with mild-to-moderate adverse effects resulting in treatment discontinuation.

The study included 60 patients with moderate-to-severe active RA who had inadequate response to methotrexate (MTX) or/and to an antitumour necrosis factor alpha (TNFα) therapy. They were randomized to receive placebo (n=20) or obefazimod at 50 mg (n=21) or 100 mg (n=19), orally once daily, in combination with MTX.

The safety of obefazimod was assessed as the primary endpoint. Efficacy endpoints included the American College of Rheumatology (ACR)20/50/70 responses, disease activity scores (DAS) 28, simplified disease activity score, European League Against Rheumatism response, DAS28 low disease activity, or remission.

A total of 11 patients stopped treatment due to AEs—nine on 100-mg obefazimod and one each on 50 mg and placebo. Most of these discontinuations were due to gastrointestinal disorders. Serious AEs occurred in one patient on placebo and another on obefazimod. There were no reports of opportunistic infection, malignancies, or death.

In terms of efficacy, significantly higher proportions of patients on ABX464 50 mg than on placebo achieved ACR20 and ACR50 responses at week 12. DAS28-C reactive protein (CRP) and DAS28-erythrocyte sedimentation rate decreased substantially, and rates of categorical DAS28-CRP response or CDAI remission increased significantly in the two obefazimod groups at week 12.

Obefazimod-treated patients showed a significant upregulation of miR-124 in blood.

The present data warrant exploration of ABX464 at 50 mg per day or less for treating patients with RA.