FDA Approves First Oral IL-23 Inhibitor for Psoriasis, Ending the Needle for Millions of Patients
Johnson & Johnson's Icotyde (icotrokinra), a once-daily oral peptide that blocks the IL-23 receptor, became the first targeted oral therapy to match biologic-level skin clearance in moderate-to-severe plaque psoriasis, marking a potential paradigm shift away from injectable treatments.
The U.S. Food and Drug Administration on March 17 approved Icotyde (icotrokinra), a first-in-class oral peptide that selectively blocks the interleukin-23 receptor, for the treatment of moderate-to-severe plaque psoriasis in adults and adolescents aged 12 and older who weigh at least 40 kg. The approval makes Icotyde the first targeted oral therapy to reach the psoriasis market with a mechanism previously available only through injectable biologic drugs.
Plaque psoriasis affects approximately 8 million Americans, with nearly one-quarter experiencing moderate-to-severe disease that requires systemic treatment. Until now, patients seeking IL-23-pathway suppression — one of the most effective strategies for sustained skin clearance — had no alternative to subcutaneous injections or intravenous infusions. Icotyde, taken as a single 200 mg tablet once daily upon waking, changes that equation.
Head-to-Head Superiority
The approval rests on four Phase 3 studies in the ICONIC clinical program, which enrolled some 2,500 patients. In the twin ICONIC-ADVANCE 1 and 2 trials, icotrokinra was tested head-to-head against deucravacitinib (Sotyktu), Bristol Myers Squibb’s oral TYK2 inhibitor that was the previous standard among non-injectable systemic treatments.
The results showed clear superiority for icotrokinra. At Week 16, 68 percent of icotrokinra patients achieved an Investigator Global Assessment (IGA) score of 0 or 1 — clear or almost clear skin — compared with 50 percent on deucravacitinib in ADVANCE 1. In ADVANCE 2, the gap was similar: 70 percent versus 54 percent. Complete skin clearance (IGA 0) was achieved by 37 percent of icotrokinra patients versus 16 to 17 percent on the comparator, while PASI 100 — a total absence of psoriatic lesions — was reached by 31 to 32 percent versus 11 to 14 percent.
Adverse event rates through Week 24 were lower with icotrokinra (57 percent of 632 patients) than with deucravacitinib (65 percent of 634 patients), with no new safety signals identified through one year of treatment. The most commonly reported side effects included headache, nausea, cough, fungal infection, and fatigue.
Durable Response Over 52 Weeks
Longer-term data from the ICONIC-LEAD study reinforced the durability of response. Among adults who achieved PASI 90 at Week 16 and continued on icotrokinra, 84 percent maintained that response at Week 52. In adolescent patients aged 12 and older, 86 percent of those on continuous treatment achieved PASI 90 by Week 52.
Jennifer Taubert, Executive Vice President at Johnson & Johnson, said the approval “marks a transformative shift in plaque psoriasis management,” enabling patients and clinicians to pursue biologic-level outcomes through an oral delivery mechanism.
Pipeline Expansion
Johnson & Johnson is pursuing additional indications for icotrokinra. The ICONIC-ASCEND trial, the first head-to-head study of an oral therapy against an injectable biologic (ustekinumab), is ongoing. Separate Phase 3 programs are evaluating the drug in psoriatic arthritis (ICONIC-PsA 1 and 2), while a Phase 2b study (ANTHEM-UC) is testing icotrokinra in moderately-to-severely active ulcerative colitis. Crohn’s disease is also listed among planned indications.
The drug carries warnings regarding infection risks and requires tuberculosis screening before initiation, consistent with other IL-23-pathway therapies.