Johnson & Johnson and Protagonist Therapeutics have announced positive topline results from two Phase 3 clinical trials, ICONIC-LEAD and ICONIC-TOTAL, evaluating icotrokinra, an investigational oral interleukin-23 (IL-23) receptor antagonist, for the treatment of moderate-to-severe plaque psoriasis. The data suggest that icotrokinra could provide a convenient oral alternative to existing injectable biologics, potentially expanding the market for IL-23-targeted therapies.
Efficacy and Safety Data
The ICONIC-LEAD trial demonstrated that icotrokinra led to clear or almost clear skin in approximately two-thirds of participants after 16 weeks of treatment. Specifically, 74% of participants treated with icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0 or 1, indicating clear or almost clear skin, by week 24. Furthermore, about half of the patients on icotrokinra hit PASI 90 (90% or greater improvement in Psoriasis Area and Severity Index scores compared to baseline measurements) by week 16, and 65% achieved this endpoint by week 24.
J&J reported that the percentage of participants experiencing side effects was similar between the icotrokinra and placebo groups, suggesting a favorable tolerability profile. Detailed results from both studies are expected to be presented at an upcoming medical meeting.
Comparison to Existing Therapies
According to David Risinger, an analyst at Leerink Partners, icotrokinra's efficacy appears "roughly comparable" to the injectable drug Stelara and potentially "superior" to oral drugs like Sotyktu and Otezla. However, Risinger noted that icotrokinra might be less effective than Skyrizi and Tremfya, which could limit its ability to directly replace those treatments. Adjusted for placebo response rates through week 16, icotrokinra’s 45% rate on PASI 90 is well below the roughly 70% rate seen in trials of Skyrizi and Tremfya.
Mechanism of Action and Market Potential
Icotrokinra functions by blocking the IL-23 signaling pathway, a mechanism similar to that of AbbVie's Skyrizi and J&J's own Tremfya, both of which are administered via injection. By offering an oral formulation, icotrokinra aims to provide a more convenient treatment option for patients with psoriasis. Risinger projects that icotrokinra could help expand the market share of IL-23 drugs, potentially contributing to J&J's forecast of greater than $5 billion in peak annual sales for the drug.
Future Development Plans
J&J is currently preparing regulatory applications based on the results of the ICONIC-LEAD and ICONIC-TOTAL trials. The company is also conducting two Phase 3 trials comparing icotrokinra to Bristol Myers Squibb's Sotyktu in patients with moderate-to-severe plaque psoriasis. Additionally, studies evaluating icotrokinra in psoriatic arthritis are scheduled to commence next year, and results from a Phase 2 trial in ulcerative colitis are anticipated before June.
