Novel oral IL-23R antagonist improves skin lesions in patients with plaque psoriasis

Elaine Soliven
01 Aug 2023
Novel oral IL-23R antagonist improves skin lesions in patients with plaque psoriasis
Dr Robert Bissonnette

Treatment with JNJ-77242113, an oral interleukin-23 receptor (IL-23R) antagonist peptide, leads to significant improvement in skin lesions, as measured by the Psoriasis Area and Severity Index (PASI) scores, in patients with moderate-to-severe plaque psoriasis, according to the FRONTIER 1 study presented at WCD 2023.

“Current therapies targeting the IL-23 pathway are effective in the treatment of immune-mediated diseases such as psoriasis. However, there are currently no orally delivered therapeutics selectively targeting this pathway,” said lead author Dr Robert Bissonnette from Innovaderm Research in Montreal, Quebec, Canada.

Hence, the current study aimed to evaluate the efficacy and safety of orally administered JNJ-77242113 in patients with moderate-to-severe plaque psoriasis, Bissonnette noted.

This double-blind, placebo-controlled, phase II dose-ranging study involving 255 patients (median age 44.3 years) with moderate-to-severe plaque psoriasis (median disease duration of 18.2 years). Participants were randomized 1:1:1:1:1:1 to either placebo or different doses of JNJ-77242113 (25, 50, and 100 mg once daily [QD] and 25 and 100 mg twice daily [BID]) for a 16-week treatment period. [WCD 2023, abstract LB01]

PASI responses
At week 16, a significantly higher proportion of patients who received the highest dose of JNJ-77242113 (100 mg) achieved a ≥75 percent improvement in skin lesions (PASI 75) than those treated with placebo (65.1 percent [QD] and 78.6 percent [BID] vs 9.3 percent; pnominal<0.001).

Similarly, significantly more patients in the JNJ-77242113 group achieved PASI 75 in both the 25-mg cohort (37.2 percent; pnominal<0.01 [QD] and 51.2 percent; pnominal<0.001 [BID] vs 9.3 percent) and 50-mg cohort (58.1 percent vs 9.3 percent; pnominal<0.001) than in the placebo group.

The JNJ-77242113 group also showed significantly higher PASI 90 and 100 response rates at week 16, with the highest response rates observed in the 100-mg BID cohort (59.5 percent vs 2.3 percent [PASI 90] and 40.5 percent vs 0.0 percent [PASI 100]; pnominal<0.001), than the placebo group.

IGA responses
At week 16, more than half of the participants treated with the highest dose of JNJ-77242113 achieved an IGA* score of 0/1 (clear/minimal) than those treated with placebo (100-mg cohort: 62.8 percent [QD] and 64.3 percent [BID] vs 11.6 percent; pnominal<0.001).

Moreover, 45.2 percent of those on JNJ-77242113 100 mg achieved an IGA score of 0 compared with none of the patients treated with placebo (pnominal<0.001).

With regard to patient-reported outcomes, JNJ-77242113 recipients had greater reductions in PSSD** symptom (-27.9 to -40.1 vs -4.2; pnominal<0.001) and sign scores (-31.7 to -50.6 vs -7.8; pnominal<0.001) than placebo recipients at week 16.

In terms of safety, both JNJ-77242113 and placebo groups showed similar rates of ≥1 adverse events (AEs; 52.4 percent vs 51.2 percent). COVID-19 (10.8 percent vs 11.6 percent) and nasopharyngitis (7.1 percent vs 4.7 percent) were the most commonly reported AEs for both treatment groups.

JNJ-77242113 was generally well tolerated in all treatment groups, with no deaths, major adverse cardiovascular events, or malignancies reported during the study, said Bissonnette.

“Overall, JNJ-77242113 is a novel, first-in-class oral IL-23R antagonist peptide that demonstrated a significant dose-response in PASI 75 at week 16 and significantly greater efficacy across all doses compared with placebo in patients with moderate-to-severe plaque psoriasis,” Bissonnette concluded.

“These results are very interesting in terms of psoriasis treatment because if this is confirmed in a phase III study, it would give us an oral alternative that would be selective for IL-23,” he added.

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