ORKA-001 Shows Sustained Skin Clearance Through Week 28 in Phase 2a Psoriasis Trial
Key Takeaways
- ORKA-001 achieved PASI 100 in 63.5% of treated participants at week 16 versus 4.8% receiving placebo.
- At week 28, 71.4% achieved PASI 100 and 87.3% achieved PASI 90, with no additional ORKA-001 dosing after week 4.
- No treatment discontinuations or injection-site reactions were reported through week 28; the small phase 2a study cannot establish long-term safety.
The investigational IL-23p19 inhibitor ORKA-001 produced high rates of complete skin clearance through week 28 in adults with moderate-to-severe plaque psoriasis who received their last dose at week 4, according to results from the phase 2a EVERLAST-A trial presented in a research poster at the 2026 Fall Clinical Dermatology Conference.1
EVERLAST-A (NCT07090330) is a randomized, double-blind, placebo-controlled study of ORKA-001, an extended-half-life humanized monoclonal antibody. The trial enrolled 84 adults with at least 10% affected body surface area, a Psoriasis Area and Severity Index (PASI) score of at least 12, and an Investigator’s Global Assessment score of at least 3. Prior exposure to anti–IL-23 therapy was excluded. Participants were randomized 3:1 to ORKA-001 600 mg (n = 63) or placebo (n = 21) at weeks 0 and 4.
Complete Clearance Rates Increased After the Final Dose
The primary endpoint, PASI 100 at week 16, was achieved by 63.5% of ORKA-001 recipients versus 4.8% of placebo recipients (P < .0001). At week 28, PASI 100 and PASI 90 rates in the original ORKA-001 group reached 71.4% and 87.3%, respectively. PASI 75 responses were 93.7% at week 16 and 95.2% at week 28. Patients receiving placebo who had not achieved PASI 90 at week 16 could cross over to ORKA-001.
During weeks 0 through 16, treatment-emergent adverse events occurred in 50.8% of ORKA-001 recipients and 57.1% of placebo recipients. During weeks 16 through 28, 36.1% of the ORKA-001-exposed safety population reported an adverse event, including two serious events. Investigators reported no treatment discontinuations or injection-site reactions through week 28.
The study is continuing through week 52 to assess durability and the potential for longer dosing intervals.
The investigators concluded that the findings indicate “potential for high rates of complete skin clearance with extended dosing intervals.”
- Strober B, Gelfand JM, Gudjonsson JE, et al. EVERLAST-A phase 2a trial: 16- and 28-week results of ORKA-001 in moderate-to-severe plaque psoriasis. Research poster supplied for editorial review. Trial registration: NCT07090330. Conference and presentation date not specified in source.