Second TYK2 Posts Deep Week-16 Clearance But Faces Payer Least-Cost Trap

InventisBio's Nomelcitinib Achieves Phase III Success in Psoriasis

InventisBio's tyrosine kinase 2 (TYK2) inhibitor, nomelcitinib, has achieved positive results in a pivotal China-based Phase III study (NCT07130604) for moderate-to-severe plaque psoriasis. The trial, involving 391 patients, met its primary endpoint with over 70% of patients on nomelcitinib achieving at least a 90% improvement in psoriasis area and severity at week 16. Additionally, over 80% were deemed 'clear' or 'almost clear' by Physician’s Global Assessment (PGA) versus placebo, demonstrating rapid response and a favorable safety profile. This success positions nomelcitinib in an increasingly competitive psoriasis market, with InventisBio also conducting a head-to-head Phase III trial against BMS' Sotyktu and a Phase II trial in the US.

• Nomelcitinib demonstrated significant efficacy in its primary endpoint, with over 70% of patients across both treatment groups achieving at least a 90% improvement in the area and severity of their psoriasis at week 16. Furthermore, a significantly higher percentage (>80%) of patients taking the drug were rated 'clear' or 'almost clear' of psoriasis by researchers using the Physician’s Global Assessment (PGA) compared to placebo.
• The JH2-selective TYK2 inhibitor exhibited a rapid onset of action, showing significant improvements in psoriasis severity and symptoms as early as week four. Importantly, the drug was found to be safe and tolerable, with researchers identifying no new safety signals associated with its use in the studied patient population.
• InventisBio is strategically advancing nomelcitinib in a highly competitive psoriasis market, which is projected to reach $30.1 billion by 2030. Following this positive data, the company is awaiting results from a second China-based Phase III trial comparing nomelcitinib head-to-head with Bristol Myers Squibb’s marketed TYK2 inhibitor, Sotyktu (deucravacitinib), and is also conducting a Phase II psoriasis trial in the US.

Nomelcitinib's Pivotal Phase III Outcomes in Plaque Psoriasis

The Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional study comparing biologic classes in moderate-to-severe psoriasis, with effectiveness assessed by Psoriasis Area and Severity Index (PASI) 90 and PASI100 response rates and durability defined as achieving therapeutic response at week 12 and its maintenance at months 6, 12, 18 and 24. Patients treated with anti-interleukin (IL)-17A biologics had significantly higher odds of achieving PASI100 and PASI90 compared to those treated with anti-IL-12/23 and anti-tumor necrosis factor (TNF)-α biologics. At 24 months, ixekizumab (IXE) showed greater PASI100 and PASI90 response rates compared to adalimumab (ADA) and ustekinumab (UST), with adjusted odds ratios of 1.9 and 2.3 for PASI100 and 2.0 and 2.5 for PASI90, respectively, and IXE-treated patients exhibited higher durability rates for PASI100 and PASI90 compared to ADA, UST, secukinumab (SEC), tildrakizumab (TILD) and guselkumab (GUS), with adjusted odds ratios (non-responder imputation [NRI]) between 1.7 and 4.3 (PASI100) and 1.6 and 4.2 (PASI90), while being similar to risankizumab (RIS).

Long-term guselkumab efficacy was evaluated in pooled post hoc analyses of the pivotal Phase 3 VOYAGE 1 and VOYAGE 2 studies, in which patients were randomized to guselkumab 100 mg every 8 weeks, placebo with week 16 crossover to guselkumab, or adalimumab with week 52 crossover to guselkumab or week 28-76 randomized withdrawal/re-treatment, followed by open-label guselkumab through week 252. At all assessment timepoints from weeks 100-252, Investigator's Global Assessment of cleared/minimal (IGA 0/1) and PASI 90 responses were similar by baseline PASI <20 vs ≥20 (IGA 0/1: 82.0%-85.4% vs 81.1%-81.4%; PASI 90: 78.6%-81.1% vs 81.4%-83.8%), IGA=3 vs =4, body surface area (BSA; <20% vs ≥20%), prior phototherapy, prior nonbiologic use, and prior biologic use. Complementary real-world data come from PERSIST, a prospective, non-interventional, German multicentre study of guselkumab, in which mean PASI score decreased from 16.4 at baseline to 3.0 by Week 28 and to 2.4 by W52, the proportion achieving absolute PASI score of ≤1 increased from 1.3% at baseline to 50.8% at W28 and to 58.4% by W52, mean Dermatology Life Quality Index (DLQI) score decreased from 13.7 to 2.8 by W28 and to 2.4 by W52, cumulative probability of drug survival was 92.4% at W52, and no new safety signals were observed.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, was evaluated in the global phase 3 trial POETYK PSO-1 (NCT03624127), with a reported subgroup analysis of Japanese patients (N=66) randomized to deucravacitinib 6 mg once daily (n=32), placebo (n=17), or apremilast 30 mg twice daily (n=17). The proportion achieving ≥75% reduction from baseline in PASI (PASI 75) was numerically higher with deucravacitinib versus placebo and apremilast at Week 16 (78.1% vs. 11.8% and 23.5%, respectively) and versus apremilast at Week 24 (78.1% vs. 29.4%), and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) was 75.0% vs. 11.8% and 35.3% at Week 16 and 75.0% vs. 29.4% at Week 24, with response rates maintained through 52 weeks. Incidence rates for adverse events per 100 person-years (PY) were comparable across groups through Week 52 (deucravacitinib, 336.8/100 PY; placebo, 321.0/100 PY; apremilast, 358.6/100 PY), with nasopharyngitis as the most frequently reported adverse event with deucravacitinib.