First-in-class oral IL-23 inhibitor safe and effective for moderate-to-severe plaque psoriasis

An investigative oral IL-23 receptor antagonist showed high efficacy and a good safety profile in a phase 2 trial. Moreover, JNJ-77242113 proved highly effective in clearing scalp psoriasis.

JNJ-77242113 is an oral IL-23 receptor antagonist peptide that selectively and potently blocks IL-23 signalling and downstream inflammatory cytokine production. Its strength and gastrointestinal stability allow for systemic IL-23 pathway blockade when administered orally. “Our study aimed to evaluate the efficacy and safety of oral JNJ-77242113 in treating patients with moderate-to-severe plaque psoriasis,” explained Dr Robert Bissonnette (Innovaderm Research, Canada) [1].

FRONTIER 1 (NCT05223868) was a randomised, double-blind, placebo-controlled, phase 2 study with 255 participants randomised into 6 groups. The participants received different dose regimens of JNJ-77242113 25 mg daily (n=43), 50 mg daily (n=43), 100 mg daily (n=43), 25 mg twice daily (n=41), and 100 mg twice daily (n=42), or placebo (n=43) through to week 16. The primary endpoint was the proportion of participants achieving a ≥75% improvement in the Psoriasis Area and Severity Index (PASI75) at week 16. Additionally, PASI90, PASI100, Investigator’s Global Assessment (IGA) score of clear or almost clear skin (0/1), IGA score 0, and scalp-specific (ss)-IGA score of 0/1 with ≥2-grade improvement from baseline at week 16 were assessed.

At week 16, the results showed a significant dose-dependent response, with all JNJ-77242113 doses demonstrating significantly higher response rates for PASI75, PASI90, PASI100, IGA scores, and ss-IGA scores compared with the placebo group (P<0.05). The proportions of participants achieving PASI75 ranged from 37.2% (in the 25 mg once daily group) to 78.6% (100 mg twice daily group), which significantly exceeded the 9.3% in the placebo group. Furthermore, those reaching PASI90 and PASI100 at week 16 in the JNJ-77242113 groups ranged from 25.6 to 59.5% and 9.8 to 40.5%, respectively, whereas in the placebo group, only 1 patient achieved PASI90 and none attained PASI100. Response rates for scalp psoriasis were also significantly higher in all doses of JNJ-77242113 compared with placebo with up to 75% of participants achieving an ss-IGA score of 0/1 with ≥2-grade improvement from baseline (see Figure).

Figure: JNJ-77242113 response rates for scalp psoriasis were significantly higher than placebo [1]



Importantly, adverse event rates were similar between the JNJ-77242113 and placebo groups, with COVID-19 and nasopharyngitis frequently reported but showing no dose-dependent trends.

"JNJ-77242113 is an excellent first-in-class oral IL-23R antagonist peptide that has proven high efficacy in treating moderate-to-severe plaque psoriasis including scalp psoriasis," Dr Bissonnette concluded.

1. 
   
   1. Bissonnette R, et al. A Phase 2, Randomized, Placebo-controlled, Dose-ranging Study of Oral JNJ-77242113 for the Treatment of Moderate-to-Severe Plaque Psoriasis: Efficacy of Overall and Scalp Psoriasis Responses from FRONTIER 1. FC08.9, EADV Congress 2023, 11-14 October, Berlin, Germany.

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Posted on 28 November 202315 February 2024