Icotrokinra, an investigational oral peptide targeting the interleukin-23 (IL-23) receptor, has demonstrated compelling efficacy in treating plaque psoriasis. The Phase 3 ICONIC-LEAD study revealed that icotrokinra significantly improved skin clearance in patients, offering a potential best-in-class oral treatment option. The results highlight the drug's ability to provide substantial skin clearance with a favorable tolerability profile in a once-daily pill.
The ICONIC-LEAD study showcased that 65% of patients treated with icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0 or 1, indicative of clear or almost clear skin, at week 16, compared to only 8% in the placebo group. Furthermore, 50% of patients on icotrokinra achieved a Psoriasis Area and Severity Index (PASI) 90 response, representing at least a 90% improvement from baseline, versus 4% in the placebo group. By week 24, 74% of patients had achieved clear skin and 65% achieved PASI90. Adverse events were similar between the treatment and placebo groups, affecting around 49% of participants in each group.
Clinical Significance and Market Potential
Dinesh Patel, President and CEO of Protagonist, emphasized the drug's potential, stating, "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." Protagonist will receive a $115 million milestone payment from Johnson & Johnson due to the successful completion of the Phase 3 study.
Psoriasis, affecting approximately 2-3% of the global population, is a chronic autoimmune condition characterized by the overproduction of skin cells, leading to the formation of plaques. Plaque psoriasis accounts for 85-90% of psoriasis cases. While there is no cure, various treatments exist, ranging from topical agents to systemic therapies. Current systemic treatments often involve injectable biologics, such as infliximab and ustekinumab. Icotrokinra aims to provide comparable efficacy through a more convenient oral route of administration.
Competitive Landscape
Bristol Myers Squibb's Sotyktu (deucravacitinib), a tyrosine kinase 2 (TYK2) inhibitor approved in 2022, is another oral option for psoriasis treatment. Protagonist and Johnson & Johnson are conducting head-to-head Phase 3 trials to compare icotrokinra with deucravacitinib, seeking to capture a significant share of the oral psoriasis medication market.
Trial Design and Endpoints
The ICONIC-LEAD trial evaluated icotrokinra's efficacy and safety in adult patients with moderate-to-severe plaque psoriasis. The primary endpoints included the proportion of patients achieving an IGA score of 0 or 1 and a PASI 90 response at week 16. Secondary endpoints assessed longer-term efficacy and safety, as well as other measures of disease severity and quality of life. The study's positive results support icotrokinra's potential as a valuable addition to the psoriasis treatment armamentarium.
