Protagonist Therapeutics and Johnson & Johnson announced impressive topline results from their Phase 2b ANTHEM-UC study evaluating icotrokinra (JNJ-2113) in adults with moderately to severely active ulcerative colitis, sending Protagonist's stock soaring by nearly 46% on Monday.
The first-in-class targeted oral peptide met its primary endpoint of clinical response across all dose groups tested. At the highest dose, icotrokinra achieved a remarkable 63.5% response rate at Week 12, compared to just 27.0% for placebo. Additionally, 30.2% of patients in the highest dose group demonstrated clinical remission, significantly outperforming the placebo group's 11.1%. Importantly, both clinical remission and response rates continued to improve through Week 28.
"These results represent a potential breakthrough for ulcerative colitis patients who currently have limited oral treatment options," said a spokesperson from the collaboration. "The sustained improvement through Week 28 is particularly encouraging for this chronic condition."
Strong Results in Psoriasis Trials
Simultaneously, Johnson & Johnson released new data from its comprehensive Phase 3 program evaluating icotrokinra in adults and adolescents with moderate-to-severe plaque psoriasis. The ICONIC-LEAD study results, presented at the 2025 American Academy of Dermatology Annual Meeting, demonstrated significant skin clearance and a favorable safety profile.
In this trial, 65% of patients receiving once-daily icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0/1 (clear or almost clear skin) and 50% reached a Psoriasis Area and Severity Index (PASI) 90 response at Week 16, compared to just 8% and 4% for placebo, respectively (P<0.001).
The skin clearance benefits continued to improve by Week 24, with 74% of icotrokinra-treated patients achieving IGA 0/1 and 65% reaching PASI 90. Perhaps most impressively, nearly half of treated patients achieved completely clear skin by Week 24 – 46% reached IGA 0 and 40% achieved PASI 100.
Competitive Advantage in Head-to-Head Comparisons
The Phase 3 ICONIC-ADVANCE 1&2 studies further strengthened icotrokinra's clinical profile by meeting all co-primary endpoints versus placebo at Week 16. The drug also demonstrated superiority to Bristol-Myers Squibb's deucravacitinib (Sotyktu) across all key secondary endpoints at Weeks 16 and 24.
Building on these successes, Johnson & Johnson is now initiating the Phase 3 ICONIC-ASCEND study, which will directly compare oral icotrokinra against the injectable biologic ustekinumab (Stelara) – potentially positioning the oral therapy as an alternative to injectable treatments.
Mechanism of Action and Safety Profile
Icotrokinra works by selectively blocking the IL-23 receptor, a key pathway in inflammatory conditions like psoriasis and ulcerative colitis. The safety profile appears favorable, with adverse events occurring at similar rates between icotrokinra (49%) and placebo groups (49%) in the psoriasis trials, with no new safety signals identified.
Financial Impact for Protagonist
The clinical successes have had a dramatic impact on Protagonist Therapeutics' financial outlook. After years of losses typical in the biotech sector, the company reported its first profit of $275 million from $434 million in revenue for 2024 – representing an impressive 63.36% margin. This financial turnaround was largely driven by a $165 million milestone payment from the icotrokinra collaboration with Johnson & Johnson.
"This represents a textbook case of biotech development economics," noted a market analyst. "After years of investment in research and clinical trials, Protagonist is now seeing the financial benefits of a successful drug candidate approaching commercialization."
Market Implications and Future Outlook
The oral administration of icotrokinra could provide a significant advantage in both the ulcerative colitis and psoriasis markets, where many current therapies require injection. If approved, icotrokinra would enter competitive markets with substantial unmet needs.
In ulcerative colitis, approximately 1 million Americans suffer from this chronic inflammatory bowel disease, with many patients struggling to achieve lasting remission with current therapies. Similarly, psoriasis affects about 8 million Americans, with moderate-to-severe cases often requiring biologics that must be injected.
As Johnson & Johnson continues to advance the clinical development program for icotrokinra, Protagonist Therapeutics stands to benefit from additional milestone payments and potential royalties if the drug reaches the market. The company's dramatic stock increase reflects investor confidence in icotrokinra's potential to transform treatment paradigms in multiple inflammatory conditions.
