Expert: mAb targeting shared p40 subunit of IL-12 (p35/p40) and IL-23 (p19/p40). Inhibits both Th1 (IL-12/STAT4/IFN-gamma) and Th17 (IL-23/STAT3/IL-17) responses. IL-12 is protective in psoriasis: Nature Communications showed IL-12 via IFN-gamma restrains gamma-delta-T17 invasion into psoriatic lesions and activates keratinocyte transcriptional programs limiting inflammation. p35 (IL-12-specific) is NOT upregulated in psoriatic lesions — disease is IL-23-driven. UltIMMa: risankizumab decisively superior (PASI 90 75% vs 42%). IL-12 blockade impairs tumor surveillance (briakinumab withdrawn over cancer signal) and Th1-mediated host defense. US LOE Sep 2023; 7+ biosimilars launched.

Everyday: Blocks the p40 subunit shared by IL-23 AND IL-12 — hitting both proteins at once. This was the first targeted approach, but turns out to be less precise than needed. THE p19/p40 STORY: IL-23 and IL-12 are two different proteins that share one building block called p40. IL-23 = p19 (unique) + p40 (shared) — drives psoriasis (bad). IL-12 = p35 (unique) + p40 (shared) — actually PROTECTIVE in psoriasis (restrains inflammation). WHY BLOCKING BOTH IS WORSE: Stelara blocks p40, shutting down BOTH IL-23 (good) and IL-12 (counterproductive). Research in Nature Communications showed IL-12 actively restrains IL-17-producing gamma-delta T cells from invading psoriatic skin. Blocking IL-12 removes this brake, partially canceling the benefit of blocking IL-23. Additionally, IL-12 drives the Th1/IFN-gamma axis essential for tumor immune surveillance and defense against intracellular pathogens (TB, listeria). CLINICAL PROOF: Selective p19 inhibitors (Skyrizi, Tremfya) beat Stelara in every head-to-head trial (UltIMMa: risankizumab 75% vs ustekinumab 42% PASI 90 at Wk16). IL-12 blockade was a liability, not an asset. BIOSIMILAR STATUS: US patent expired Sep 2023. 7+ biosimilars launched Jan-Feb 2025. Revenue declining from $10.9B peak (2023) to ~$6-7B (2025).

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Primary EP: [{"id":"pasi75-w12","name":"PASI 75 at Week 12","type":"PRIMARY","unit":"%","results":[{"value":67.1,"arm_id":"ust45-arm","p_value":0.001},{"value":66.4,"arm_id":"ust90-arm","p_value":0.001},{"value":

First-gen IL-12/23 (p40) inhibitor. Approved 2009 — 15+ years on market. PASI 90 ~42-50% Wk16. Now the floor comparator: beaten by every newer biologic in H2H trials (UltIMMa, VOYAGE, BE VIVID, ECLIPSE). Mechanism is suboptimal: blocks both IL-23 (the psoriasis driver) and IL-12 (which is actually protective — restrains inflammation via IFN-gamma). Peak revenue $10.9B (2023). US patent expired Sep 2023; 7+ biosimilars launched Jan-Feb 2025 (Wezlana, Pyzchiva, Selarsdi, Otulfi, Yesintek, etc.). Biosimilar discounts 46-90%. Revenue declining rapidly: $10.3B (2024) → ~$6.5B (2025). Still used in IBD (CD, UC) where biosimilar switching is slower, but declining there too.