Encouraging results for first oral IL-23 receptor antagonist in plaque psoriasis

A first-in-class, investigational, oral, IL-23 receptor antagonist peptide, provisionally named JNJ-77242113, was associated with improved efficacy outcomes compared with placebo in patients with moderate-to-severe plaque psoriasis, in a phase 2b study.

“There are currently no orally delivered therapeutics for psoriasis selectively targeting the IL-23 pathway,” said Dr Robert Bissonnette (Innovaderm Research, Canada) [1]. JNJ-77242113 is a first-in-class, oral, IL-23 antagonist peptide. “Because of the gastrointestinal stability and potency of this investigational agent, it is able to deliver systemic IL-23 pathway blockade via oral dosing,” added Dr Bissonnette.

The FRONTIER 1 trial (NCT05223868) randomised 255 patients with moderate-to-severe plaque psoriasis 1:1:1:1:1:1 to 1 of 5 doses of JNJ-77242113, ranging from 25 mg once daily to 100 mg twice daily, or a placebo. Dr Bissonnette and colleagues looked primarily at the proportion of participants achieving Psoriasis Area and Severity Index (PASI)75 after 16 weeks of treatment [2].

A significant dose-response was observed for PASI75 after 16 weeks of therapy: 9.3% of the participants on placebo reached PASI75 compared with 37.2% (P<0.01) and 78.6% (P<0.001) of the participants on the lowest dose and highest dose of JNJ-77242113, respectively (see Figure). Furthermore, 40.5% of the participants on the highest dose of JNJ-77242113 reached PASI100 compared with none on placebo.

Figure: Proportion of participants achieving PASI75 at week 16 [2]

BID, twice daily; QD, once daily.

Dr Bissonnette added that patients responded quickly to the agent, with over 20% of the participants in the high-dose group achieving PASI75 at week 4. In terms of Investigator’s Global Assessment (IGA) response, 64.3% of the participants in the highest dose group achieved a score of 0 or 1, compared with 11.6% of the participants in the placebo. In addition, 45.2% of the participants in the high-dose group reached an IGA score of 0, whereas none of the participants on placebo reached this score.

No dose-related trends were observed regarding adverse events. The proportions of participants who experienced at least 1 adverse event were comparable for the 6 arms of the study. COVID-19 (10.8%) and nasopharyngitis (7.1%) were the most frequently reported adverse events.

In conclusion, JNJ-77242113 showed promising efficacy results in this phase 2b study and was well tolerated in a population of patients with moderate-to-severe plaque psoriasis.

1. Fourie A, et al. Presented at ISID meeting; May 10-13, 2023; Tokyo, Japan. ID1109.
2. 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: FRONTIER 1. Late-breaker Session 1, WCD 2023, 3–8 July, Singapore, Singapore.