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Obefazimod takes the spotlight as promising UC treatment

Presented by
Prof. Séverine Vermeire, UZ Leuven, Belgium
UEGW 2023
Phase 2
Obefazimod displayed ongoing efficacy over 2 years of treatment in participants with moderately to severely active ulcerative colitis (UC) in an open-label phase 2b study. The investigational agent was well tolerated, and no worrisome safety signals were observed.

“New oral treatments with novel mechanisms of action are needed to treat patients with UC,” expressed Prof. Séverine Vermeire (UZ Leuven, Belgium). “The investigational agent obefazimod evokes an enhanced expression of miR-124, resulting in a reduction of pro-inflammatory cytokines.” Obefazimod has demonstrated encouraging efficacy and safety data after 8 weeks of induction therapy in participants with UC in a phase 2b study [1]. All participants who completed the phase 2b study could then enrol in the open-label, 96-week maintenance study, irrespective of their clinical response. Prof. Vermeire presented the current findings of the open-label study [2]. Clinical remission was based on the Modified Mayo score (MMS) and defined as a stool frequency subscore ≤1, rectal bleeding subscore (RBS)=0, and an endoscopic subscore ≤1. Clinical response was defined as a decrease in the MMS ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1. Endoscopic remission and improvement were assessed as endoscopic subscores of 0 and ≤1, respectively. The 217 participants received 50 mg of obefazimod once daily, orally administered. “Over 90% of these participants had been exposed to 2 or more biologic therapies and/or JAK inhibitors,” she stressed.

The clinical remission rates at weeks 48 and 96 were 54.8% and 52.5%, respectively. Other outcomes displayed promising efficacy results for obefazimod as well: at weeks 48 and 96, clinical response rates were 82% and 72.8%, respectively; endoscopic improvement rates were 61.3% and 59%; and endoscopic remission rates were 33.2% and 35.9%.

In bio-naïve participants, the corresponding rates of efficacy outcomes were 63.8% for the clinical remission rate, 77.3% for the clinical response rate, 68.9% for the endoscopic improvement rate, and 48.7% for the endoscopic remission rate. For bio-experienced participants, the rates were numerically lower but still promising, according to Prof. Vermeire, with 38.8%, 67.3%, 46.9%, and 20.4%, respectively (see Figure). She added that 48.2% of the participants who were not in clinical remission at baseline (n=168) achieved clinical remission at 2 years of therapy.

Figure: Efficacy results in bio-naïve and bio-refractory participants at 2 years [2]

Treatment-emergent adverse events (TEAEs) were reported in 68.7% of the participants over the 2-year course of the study. COVID-19 (14.3%), headache (11.5%), and UC worsening (7.8%) were the most common TEAEs. Nearly 8% of participants had TEAEs leading to study discontinuation. Finally, serious AEs occurred in 8.7% of the participants, including a wide variation of events from which no concerning pattern could be distilled.

“At week 96, obefazimod showed promising safety and efficacy results in participants with UC. The agent is currently being investigated in phase 3 trials,” concluded Prof. Vermeire.

    1. Vermeire S, et al. Lancet Gastroenterol Hepatol. 2022;7:1024–-1035.
    2. Vermeire S, et al. Obefazimod in patients with moderate-to-severe ulcerative colitis: efficacy and safety analysis from the 96-week open-label maintenance phase 2b study. OP077, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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