JNJ-2113 Shows Promising Phase 3 Results for Plaque Psoriasis

Image Credit: © DermNet

Protagonist Therapeutics announced positive topline results from its phase 3 clinical trials, ICONIC-LEAD and ICONIC-TOTAL, evaluating JNJ-2113 (icotrokinra, formerly PN-235), a novel, oral peptide targeting the IL-23 receptor. The studies were conducted in patients aged 12 years and older with moderate to severe plaque psoriasis (PsO). The company said the promising results of these trials, in collaboration with Johnson & Johnson, suggest that JNJ-2113 may be an innovative therapy for this chronic inflammatory skin condition.¹

"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 icotrokinra'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," said Dinesh V. Patel, PhD, president and CEO of Protagonist, in a press release. "These results also continue to validate Protagonist's innovative peptide technology platform and its effectiveness in creating highly differentiated new chemical entities to address unmet needs in various disease areas."

Study Design and Primary Outcomes

Both ICONIC-LEAD and ICONIC-TOTAL were designed to assess the safety and efficacy of JNJ-2113 in treating moderate to severe PsO. According to the ICONIC-LEAD trial, patients received once-daily JNJ-2113, which demonstrated substantial skin clearance compared to placebo. At week 16, researchers stated that 64.7% of patients treated with JNJ-2113 achieved an Investigator Global Assessment (IGA) score of 0/1, indicating clear or almost clear skin, compared to just 8.3% in the placebo group. Additionally, 49.6% of JNJ-2113-treated patients achieved a Psoriasis Area and Severity Index (PASI 90), a significant reduction in skin lesions, versus only 4.4% of those on placebo. Researchers found these results were sustained and improved at week 24, with 74.1% achieving IGA scores of 0/1 and 64.9% reaching PASI 90.

The company wrote that the ICONIC-TOTAL study similarly showed that JNJ-2113 met the primary endpoint of achieving IGA scores of 0/1 at week 16. The results across both studies demonstrate JNJ-2113’s potential as an effective treatment option for PsO, with skin clearance outcomes that significantly outperformed placebo.

Safety Profile

Researchers stated that safety data from both phase 3 studies were consistent with previous phase 2b FRONTIER studies.^2-3 The incidence of treatment-emergent adverse events (TEAEs) was similar between the JNJ-2113 and placebo groups. At week 16, 49.3% of JNJ-2113-treated patients and 49.1% of placebo patients experienced a TEAE, suggesting that JNJ-2113 was well tolerated. The company stated this favorable safety profile enhances its potential as a long-term treatment option for patients with moderate to severe PsO.

Clinical Implications and Future Prospects

The company wrote that these positive phase 3 results reinforce the efficacy and safety of JNJ-2113, supporting its development as a best-in-class oral therapy for PsO. As a first-in-class oral peptide, JNJ-2113 selectively blocks the IL-23 receptor, a crucial player in the inflammatory pathways of psoriasis. Researchers stated the potential for significant skin clearance, combined with demonstrated tolerability, makes JNJ-2113 a promising treatment for patients seeking an oral alternative to traditional biologics. 

Looking ahead, Protagonist noted JNJ-2113 is also being evaluated in other clinical indications. Notably, the phase 2b ANTHEM study for ulcerative colitis is expected to report topline results in early 2025. Additionally, the phase 3 ICONIC-ADVANCE studies compare JNJ-2113 against placebo and deucravacitinib in moderate to severe PsO, with results anticipated in the first half of 2025. A new phase 3 program in psoriatic arthritis will begin in 2025, expanding the therapeutic potential of JNJ-2113.

"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 icotrokinra in psoriatic arthritis," added Dr. Patel. "Our enthusiasm for icotrokinra is high heading into 2025, with 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."

Conclusion

The promising phase 3 results from the ICONIC studies validate JNJ-2113's potential as an effective, oral treatment for moderate to severe PsO. With its compelling efficacy data and favorable safety profile, the company stated JNJ-2113 could significantly alter the treatment landscape for PsO and other inflammatory diseases.

References

1. Protagonist announces positive topline results from phase 3 ICONIC studies of icotrokinra (JNJ-2113), a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor in plaque psoriasis. News Release. Protagonist Therapeutics. Published November 18, 2024. Accessed November 19, 2024. https://www.protagonist-inc.com/news/protagonist-announces-positive-topline-results-from-phase-3-iconic-studies-of-icotrokinra-jnj-2113-a-first-in-class-investigational-targeted-oral-peptide-that-selectively-blocks-the-il-23-receptor
2. New data shows JNJ-2113, the first and only investigational targeted oral peptide, maintained skin clearance in moderate-to-severe plaque psoriasis through one year. News Release. Johnson and Johnson. Published March 9, 2024. Accessed November 19, 2024. https://www.jnj.com/media-center/press-releases/new-data-shows-jnj-2113-the-first-and-only-investigational-targeted-oral-peptide-maintained-skin-clearance-in-moderate-to-severe-plaque-psoriasis-through-one-year
3. Investigational targeted oral peptide JNJ-2113 demonstrated positive results in moderate-to-severe plaque psoriasis in phase 2b study published in New England Journal of Medicine. News Release. Johnson and Johnson. Published February 7, 2024. Accessed November 19, 2024. https://www.jnj.com/media-center/press-releases/investigational-targeted-oral-peptide-jnj-2113-demonstrated-positive-results-in-moderate-to-severe-plaque-psoriasis-in-phase-2b-study-published-in-new-england-journal-of-medicine