Positive Phase 3 Results Announced for JNJ-2113 Treatment of Psoriasis

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An announcement has been made by Protagonist Therapeutics, Inc. that following the company’s collaboration with Johnson & Johnson on the ICONIC-LEAD and ICONIC-TOTAL studies, positive findings from these phase 3 trials have been identified for patients with psoriasis treated with the oral peptide JNJ-2113 (icotrokinra).¹

JNJ-2113, formerly known as PN-235, is a first-in-class medication designed to selectively inhibit the interleukin (IL)-23 receptor, a receptor driving inflammatory responses in psoriasis. It was formulated to address the needs of those in the age range of 12 years and older suffering from moderate to severe plaque psoriasis.

“These positive Phase 3 results confirm the compelling efficacy and safety trends that were observed with the previous Phase 2b FRONTIER-1 and -2 studies, highlighting (JNJ-2113’s) potential as a best-in-class oral agent providing an ideal combination of significant skin clearance with demonstrated tolerability in a once-daily pill for treating plaque psoriasis,” Dinesh V. Patel, PhD, president and CEO of Protagonist, said in a statement.¹

In March 2024, 52-week results on JNJ-2113 showed that the oral peptide treatment resulted in significant levels of skin clearance over the course of 52 weeks in adults with moderate-to-severe psoriasis. These findings had been presented at the 2024 American Academy of Dermatology (AAD) Annual Meeting.²

In the latest phase 3 ICONIC-LEAD study, 684 subjects were assessed with the aim of evaluating medication’s safety and efficacy versus placebo for moderate-to-severe psoriasis. A 90% Psoriasis Area and Severity Index improvement (PASI 90) and an Investigator's Global Assessment Scale (IGA) score of 0 or 1 with a minimum 2-grade improvement were their co-primary endpoints.

In the phase 3 ICONIC-TOTAL trial, the efficacy and the safety of JNJ-2113 were compared to placebo in the treatment of 311 individuals with psoriasis as well. However, this study involved subjects with at least a moderate level of disease severity impacting special areas such as the scalp, genital, and/or hands and feet. They also had to have an overall IGA score of 0 or 1 and at least a 2-grade improvement.

Following the ICONIC-LEAD study, investigators concluded that daily administration of JNJ-2113 led to significant levels of clearance compared to those given a placebo. This was noted among both adults and adolescents, and by the 16-week mark they found that 64.7% of participants achieved IGA scores of 0/1.Additionally, the ICONIC-LEAD team reported that 49.6% of subjects successfully achieved PASI 90, as opposed to only 8.3% and 4.4% of those on placebo, respectively.¹

By the 24-week mark, the research team found that 74.1% of subjects reported IGA scores of 0/1 and 64.9% achieved PASI 90. Safety data on JNJ-2113 from this analysis aligned with earlier safety data from the phase 2 FRONTIER trials, with rates of adverse events between JNJ-2113 (49.3%) and placebo (49.1%) shown to be comparable by Week 16.¹

In a similar vein, the ICONIC-TOTAL study results suggested that JNJ-2113 met its primary endpoint of IGA 0/1 at the 16-week mark compared to those treated with placebo, highlighting the medication’s efficacy. Additional results are slated for future presentations.¹

Findings drawn from the phase 3 ICONIC-ADVANCE 1 and 2 studies, comparing the medication’s performance against those of both placebo and deucravacitinib among those with moderate-to-severe psoriasis, are slated for 2025 alongside a new phase 3 trial for psoriatic arthritis (ICONIC-PsA).¹

“We’re very pleased with the ICONIC-LEAD and ICONIC-TOTAL Phase 3 results, and the decision of our partner to initiate a Phase 3 program for (JNJ-2113) in psoriatic arthritis,” Patel said in a statement. “Our enthusiasm for (JNJ-2113) is high heading into 2025, with upcoming Phase 2b ulcerative colitis results, presentation of ICONIC Phase 3 results at medical conferences, topline results from psoriasis superiority studies against deucravacitinib and a potential psoriasis NDA submission.”¹

References

1. ^{Protagonist Announces Positive Topline Results From Phase 3 ICONIC Studies of Icotrokinra (JNJ-2113) in Plaque Psoriasis, a First-in-Class Investigational Targeted Oral Peptide That Selectively Blocks the IL-23 Receptor. Protagonist Therapeutics, Inc. November 19, 2024. https://www.biospace.com/press-releases/protagonist-announces-positive-topline-results-from-phase-3-iconic-studies-of-icotrokinra-jnj-2113-in-plaque-psoriasis-a-first-in-class-investigational-targeted-oral-peptide-that-selectively-blocks-the-il-23-receptor.}
2. ^{Ferris, L et al. A Phase 2b, Long-term Extension, Dose-ranging Study of Oral JNJ-77242113 for the Treatment of Moderate-to-Severe Plaque Psoriasis: FRONTIER 2. Oral presentation (Abstract #S026) at the American Academy of Dermatology (AAD) 2024 Annual Meeting. March 2024. Date accessed: November 19, 2024.}