$165 Million Milestone! Johnson & Protagonist's First Oral IL23 Psoriasis Phase 3 Success!

On November 19, Johnson & Johnson and Protagonist jointly announced that the pivotal Phase 3 ICONIC study of Icotrokinra (JNJ-2113, formerly known as PN-235) has achieved positive top-line results. This Phase 3 study reached the co-primary endpoints of Psoriasis Area and Severity Index (PASI) 90 and Investigator Global Assessment (IGA) 0/1 response at Week 16, with the response rate continuing to improve through Week 24. 

According to their press release, JNJ-2113 is the first selective IL-23 receptor-targeted oral peptide for adults and adolescents aged 12 years and older with moderate-to-severe plaque psoriasis (PsO).

Compared to placebo, once-daily Icotrokinra showed significant skin clearance rates in adults and adolescents with moderate-to-severe plaque psoriasis. 

• By Week 16, nearly two-thirds (64.7%) of patients receiving Icotrokinra achieved an IGA score of 0/1 (clear or almost clear skin), and 49.6% of patients achieved PASI90, while the placebo group showed only 8.3% and 4.4%, respectively. The ICONIC-TOTAL study in patients with refractory plaque psoriasis also reached the IGA 0/1 endpoint at Week 16. 
• By Week 24, the response rates further increased, with 74.1% of Icotrokinra-treated patients achieving IGA 0/1, and 64.9% achieving PASI90. The safety data were consistent with the Phase 2 FRONTIER1 and 2 studies. 

The incidence of adverse events (AE) was similar between Icotrokinra and placebo, with 49.3% and 49.1% of participants experiencing treatment-emergent adverse events (TEAEs) at Week 16.

The combined results of ICONIC-LEAD and ICONIC-TOTAL are being prepared for presentation at an upcoming medical conference. Additional studies in the ICONIC Phase 3 clinical development program are ongoing, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will evaluate the safety and efficacy of Icotrokinra compared to placebo and deucravacitinib in moderate-to-severe plaque psoriasis. The ICONIC-PsA Phase 3 program will begin in early 2025 and will assess the treatment effect of Icotrokinra in psoriatic arthritis. 

JNJ-2113 is a peptide oral IL-23 receptor antagonist. The IL-23/IL-23R signaling pathway plays a key role in the pathogenesis of immune-mediated inflammatory diseases, including psoriasis, psoriatic arthritis, and inflammatory bowel disease.

In 2017, Janssen signed a deal worth $980 million with Protagonist Therapeutics to jointly advance the development of the oral IL-23 receptor antagonist drug. In December 2021, Protagonist and Janssen decided to proceed with PN-235 as a candidate drug.

According to Protagonist’s press release, with the positive results from the Phase 3 ICONIC study, the company has received a $165 million milestone payment from Janssen. In addition, Protagonist remains eligible to receive up to $630 million in future development and sales milestone payments, as well as tiered royalties on global net sales ranging from 6-10%. 

Liza O'Dowd, Janssen's Vice President of Innovation and Immunodermatology, said: “We are excited to see the positive Phase 3 results for once-daily Icotrokinra, which align with our expectations based on its Phase 2 data. Most moderate-to-severe plaque psoriasis patients are eligible for advanced therapies but remain undertreated. Icotrokinra has the potential to provide a once-daily oral therapy that can help meet the needs and preferences of plaque psoriasis patients.”

"These positive Phase 3 results confirm the compelling efficacy and safety trends observed in the earlier Phase 2b FRONTIER-1 and -2 studies, highlighting Icotrokinra's potential as a best-in-class oral therapy, an ideal oral drug for treating plaque psoriasis with significant skin clearance and favorable tolerability with once-daily dosing," said Dr. Dinesh V. Patel, President and CEO of Protagonist Therapeutics.