Executive summary

As of 2026-05-14, the IL-23 landscape includes six approved branded pathway products in major markets: ustekinumab, guselkumab, risankizumab, tildrakizumab, mirikizumab, and icotrokinra. Mechanistically, that now spans IL-12/23 p40 blockade, selective IL-23p19 blockade, and direct oral IL-23 receptor antagonism. 1234

Commercially, AbbVie’s Skyrizi is the clear leader. Using public filings, Skyrizi reached about $17.56 billion in 2025 global revenue, compared with Johnson & Johnson’s 2025 sales of $6.08 billion for Stelara and $5.16 billion for Tremfya. Almirall reported €234.4 million of 2025 Ilumetri net sales in Europe. Lilly’s 2025 10-K did not separately disclose Omvoh product-level annual sales, and Icotyde is too new to have a meaningful full-year commercial base. 5462

Clinically, selective IL-23 blockade has become a core mechanism in plaque psoriasis and a rapidly strengthening option in Crohn’s disease and ulcerative colitis. Payer behavior, however, is unlikely to treat the class as homogeneous: ustekinumab is now a biosimilar-exposed legacy asset, while p19 antibodies and oral IL-23R blockade remain premium-positioned and are still differentiating on breadth, convenience, and evidence generation. 7489

Recent regulatory movement reinforces the direction of travel. The FDA approved Omvoh for Crohn’s disease in January 2025, Icotyde on March 17, 2026, as the first oral IL-23 receptor antagonist for plaque psoriasis, and Stelara for pediatric Crohn’s disease in April 2026. Those approvals collectively point toward broader bowel use, greater route flexibility, and deeper lifecycle management across the pathway. 10911

Approved IL-23 inhibitors

Approved IL-23-pathway products now span three mechanistic layers. Ustekinumab blocks the shared IL-12/23 p40 subunit. Guselkumab, risankizumab, tildrakizumab, and mirikizumab selectively bind IL-23p19. Icotrokinra is distinct as an oral peptide antagonist of the IL-23 receptor. 123

Ustekinumab remains the broadest legacy label across skin, joint, and bowel disease. In psoriasis, PHOENIX reported week-12 PASI 75 rates of 67% and 76% versus 4% with placebo. In Crohn’s disease, IM-UNITI maintenance showed week-44 remission of 53.1% with every-8-week dosing and 48.8% with every-12-week dosing versus 35.9% with placebo. In ulcerative colitis, UNIFI showed week-8 clinical remission of about 15.5% to 15.6% versus 5.3% with placebo and week-44 remission of 43.8% with every-8-week dosing versus 24.0% with placebo. Key label warnings include serious infections, malignancy, hypersensitivity, PRES, and noninfectious pneumonia. 12131415

Guselkumab is Johnson & Johnson’s growth IL-23 franchise. VOYAGE showed PASI 90 at week 16 in 73% versus 3% with placebo, and VOYAGE 2 showed PASI 90 in 64% versus 42% with adalimumab at week 16. The franchise is now approved across plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s disease in major Western markets, with additional work on fully subcutaneous bowel regimens. Major safety issues on current labeling center on infections, TB evaluation, hypersensitivity, and liver monitoring in IBD practice. 1617184

Risankizumab is the commercial leader and the most globally entrenched selective IL-23 antibody. AbbVie’s 2025 10-K states that Skyrizi is approved in North America, the EU, and Japan for plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. The same filing notes quarterly SC dosing in psoriatic disease and IV induction followed by every-8-week subcutaneous on-body maintenance in IBD. In phase 3 PsA studies, ACR20 at week 24 reached 57% and 51% across KEEPsAKE 1 and 2. Major label risks include serious hypersensitivity, infection, TB evaluation, and liver toxicity monitoring in IBD use. 119

Tildrakizumab remains a psoriasis-focused asset. In reSURFACE 1, PASI 75 at week 12 was achieved by 62% on 200 mg and 64% on 100 mg versus 6% with placebo. Sun Pharma also states that the product has marketing authorization in more than 55 jurisdictions, including the United States, Europe, Japan, and India. Commercially it is smaller than the leading IL-23 brands, but it still benefits from the class’s strong psoriasis positioning. Major core risks are hypersensitivity, infections, TB evaluation, and vaccine considerations. 2021

Mirikizumab is Lilly’s IBD-focused IL-23p19 product. Lilly’s 2025 10-K describes Omvoh as indicated for moderately to severely active ulcerative colitis and Crohn’s disease in adults; the same filing notes Crohn’s disease approval in the U.S., EU, and Japan. In LUCENT, mirikizumab was superior to placebo in induction and maintenance for ulcerative colitis; commonly cited figures are 24.2% versus 13.3% clinical remission at week 12 and 49.9% versus 25.1% at maintenance week 40. For Crohn’s disease, publicly reported phase 3 data supported approval with clinically meaningful remission and endoscopic benefit through one year. Label-level practical concerns include infections, TB evaluation, and liver monitoring. 22210

Icotrokinra is the most important new entrant because it changes the route-of-administration economics of the class. FDA approved Icotyde on March 17, 2026, for moderate-to-severe plaque psoriasis in adults and pediatric patients 12 years and older who weigh at least 40 kg and are candidates for systemic therapy or phototherapy. The approved dose is 200 mg orally once daily, taken on an empty stomach. The phase 3 psoriasis program showed IGA 0/1 in 64.7% versus 8.3% with placebo and PASI 90 in 49.6% versus 4.4% at week 16. The label’s core warnings are infections, TB evaluation, and avoidance of live vaccines; serious infections in the 16-week placebo-controlled trials were 0.2% with Icotyde versus 0.4% with placebo. 9323

Table note: regional indication mixes outside the explicitly cited major-market public sources were marked unspecified where verification was incomplete. Table values were compiled from current company filings, FDA labeling or approval materials, HCP materials, and pivotal publications. 12312131620

Late-stage and notable pipeline

The late-stage IL-23 pipeline is no longer just a contest among new antibodies. The highest-conviction development theme is additional-indication expansion of newly approved oral IL-23 receptor blockade through icotrokinra, especially in psoriatic arthritis and inflammatory bowel disease. That matters strategically because success would create the first oral multi-indication IL-23 franchise rather than a single-indication plaque-psoriasis oral product. 24

The most visible regional challenger is picankibart, also known as IBI112 and marketed in company communications as PECONDLE. Innovent reported registrational phase 3 success in psoriasis and separately highlighted a phase 3 anti-IL-17-switch study, suggesting a China-centered launch strategy with an emphasis on difficult-to-treat populations. Ex-China regulatory status was not fully specified in the sources reviewed, so this summary treats it conservatively as a launch-transition or regional late-stage asset rather than a fully global commercial entrant. 2526

Lifecycle expansion remains important even for smaller brands. Sun Pharma announced FDA acceptance of an sBLA for tildrakizumab in active psoriatic arthritis in March 2026 after earlier scalp and nail psoriasis label expansions. That does not yet change the current marketed footprint, but it shows how even secondary IL-23 franchises are trying to broaden clinical relevance when the core plaque-psoriasis space is increasingly concentrated. 21

Long-acting engineering is the main earlier-stage differentiator. Oruka reported positive EVERLAST-A data with ORKA-001 in 2026, including PASI 100 in 63.5% and PASI 90 in 83% at week 16 with placebo-like tolerability. The cited company release did not clearly state the formal phase label in the snippet available, so this report classifies ORKA-001 as notable mid-stage proof-of-concept rather than a confirmed late-stage program. 27

Publicly visible comparative work is also increasing. The existence of active studies comparing guselkumab and risankizumab in Crohn’s disease suggests that simple class membership is no longer enough for differentiation and that comparative bowel efficacy may become a more important commercial battleground. 28

Pipeline table note: phase labels were reported conservatively from the public materials reviewed. 272521

Market and commercial landscape

Commercial concentration is high. Using public company disclosures for 2025, Skyrizi generated approximately $17.56 billion globally, versus $6.08 billion for Stelara and $5.16 billion for Tremfya. That revenue spread matters because it reflects not only leadership in psoriasis but also broad uptake in Crohn’s disease and ulcerative colitis, where label breadth has become a major commercial multiplier. 54

Tildrakizumab is materially smaller but still relevant. Almirall reported 2025 Ilumetri net sales of €234.4 million and explicitly described anti-IL-23 antibodies as the leading class in advanced psoriasis. That is commercially important because it suggests the class remains healthy even for smaller brands, though scale is now far below Skyrizi, Tremfya, and the legacy Stelara base. 6

Pricing remains premium where current U.S. list-price pages were available. AbbVie listed Skyrizi at $23,838.42 per dose as of January 6, 2026. Johnson & Johnson listed Tremfya at $14,566.44 per single SC injection or IV infusion as of March 2025, with a Crohn’s disease induction pack at $29,132.88. Lilly listed Omvoh at $9,593.22 for one 300 mg/15 mL infusion. Current official list-price capture was incomplete for Stelara and Ilumya in the sources reviewed, so those are marked unspecified here rather than estimated. 293031

Payer dynamics are being reshaped by ustekinumab biosimilars and public-sector cost pressure. Johnson & Johnson’s 2025 annual report attributes Stelara’s 41.3% sales decline to biosimilar competition and Medicare Part D redesign, and notes broader global biosimilar pressure. CivicaScript separately announced a low, transparent WAC for ustekinumab-aauz, underscoring how legacy IL-23-pathway economics are diverging from the still-protected p19 brands. 48

Public cost-effectiveness work is thinner than the commercial data. ICER’s most relevant public review remains the 2018 psoriasis update, which concluded that guselkumab and risankizumab offered superior net health benefit versus TNF-alpha inhibitors, while tildrakizumab was judged comparable or inferior to guselkumab and risankizumab on relative net health benefit. ICER’s later Unsupported Price Increase report also discussed Tremfya’s pricing trajectory. No equally current, agent-specific public ICER review was identified in the sources reviewed for the newest bowel-disease IL-23 entrants. 32

Competitive positioning and unmet needs

In dermatology, IL-23 therapy is now a default high-efficacy advanced-treatment mechanism because it combines strong PASI 90 and PASI 100 performance with long maintenance intervals and durable control. Commercially, the winner so far is Skyrizi, but Tremfya remains competitive on breadth and Johnson & Johnson has now added a second attack angle with oral icotrokinra. Tildrakizumab remains clinically useful but is competitively disadvantaged by narrower labels and lower brand momentum. 1612094

In psoriatic arthritis, IL-23 inhibitors fit best when skin disease is prominent and peripheral domains dominate. EULAR’s 2024 update explicitly states that relevant skin psoriasis should orient therapy toward IL-23p40, IL-23p19, IL-17A, and IL-17A/F biologics. The practical implication is that when axial disease, uveitis, or very rapid multi-domain control dominate the clinical picture, TNF inhibitors, IL-17 inhibitors, or JAK inhibitors may still be preferred depending on the full comorbidity profile. 33

In inflammatory bowel disease, the balance is shifting rapidly toward IL-23-based therapy. The 2025 AGA living guideline recommends ustekinumab, risankizumab, mirikizumab, and guselkumab among the advanced options for moderate-to-severe Crohn’s disease. That is strategically important because IL-23 now offers credible bowel efficacy without the same boxed-warning burden as JAK inhibitors and without the IBD-exacerbation concerns associated with IL-17 blockade. 7

The main unmet needs are sequencing evidence, extraintestinal precision, and convenience trade-offs. There are still few high-quality head-to-head IL-23 studies in bowel disease, little public biomarker guidance on which IL-23 inhibitor to choose first, and limited pediatric evidence outside ustekinumab’s broadening label. The arrival of oral IL-23R therapy may improve adherence and reduce administration friction, but real-world comparative persistence and access rules remain unsettled. 28119

Regulatory trends and implications

The recent regulatory pattern is expansion rather than class maintenance. The FDA approved Omvoh for Crohn’s disease in January 2025, approved Icotyde on March 17, 2026, as the first oral IL-23 receptor antagonist for plaque psoriasis, and approved Stelara for pediatric Crohn’s disease in April 2026. Those actions show three parallel vectors: deeper IBD penetration, oral convenience, and pediatric broadening. 10911

Regulators are also rewarding administration simplification and line-extension strategy. Johnson & Johnson’s materials show ongoing work on fully subcutaneous induction for Tremfya in ulcerative colitis and Crohn’s disease, while Sun Pharma is pursuing an active-psoriatic-arthritis expansion for tildrakizumab after earlier scalp and nail psoriasis updates. That means future differentiation may come as much from route, device, and sequencing practicality as from novel biology. 2117

For clinicians, the main implication is that IL-23 selection is becoming more phenotype-specific and less class-generic. For payers, the implication is a split market: biosimilar-exposed ustekinumab on one side and premium, still-protected p19 or IL-23R assets on the other. For researchers, the key agenda is comparative evidence across brands, performance in overlap populations, and real-world persistence after switching from TNF, IL-17, or JAK mechanisms. 4728

There is also an IRA-related reimbursement signal. Johnson & Johnson’s annual report notes that CMS indicated removal of Xarelto and Stelara from the Selected Drug List beginning in 2027 after biosimilar-related exclusivity changes, showing how rapidly the payer environment can change once a pathway product loses commercial protection. 4

Open questions and limitations

This summary prioritizes primary sources and major journals, but some region-specific indication details were incomplete in the public materials reviewed, especially for Japan, China, and ex-U.S. lifecycle expansions outside the core U.S./EU disclosures. Those entries are marked unspecified rather than extrapolated. 1221

Product-level 2025 sales were directly disclosed for Skyrizi, Stelara, Tremfya, and European Ilumetri, but not for Omvoh in Lilly’s 2025 10-K. Current official list-price capture was also incomplete for Stelara and Ilumya from the sources reviewed. The result is a high-confidence directional commercial picture, but not a complete class revenue ledger. 4625

Head-to-head evidence inside the class remains limited, especially in bowel disease, so several competitive conclusions are still inference-based rather than definitively resolved. Ongoing comparative studies are therefore among the most important forward-looking signals in the landscape. 28