ORKA-001 achieved 71.4% PASI 100 and 87.3% PASI 90 at Week 28 in moderate-to-severe plaque psoriasis despite no dosing after Week 4.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
Oruka Therapeutics reported that its half-life-extended IL-23p19 monoclonal antibody ORKA-001 continued to deepen clinical responses in moderate-to-severe plaque psoriasis through Week 28, despite no treatment after Week 4. In the Phase 2a EVERLAST-A study, PASI 100 increased to 71.4% and PASI 90 to 87.3%, supporting further evaluation of the drug’s durability and infrequent dosing potential.
Durable IL-23 Blockade Shows Continued Clinical Response
ORKA-001 is a half-life-extended monoclonal antibody targeting interleukin-23 p19 (IL-23p19), a cytokine pathway that plays a central role in the inflammatory cascade driving plaque psoriasis. IL-23 inhibition has become an established treatment strategy for moderate-to-severe disease, but treatment frequency remains an important consideration for long-term management.
The Week 28 findings from EVERLAST-A are notable because patients received only two 600 mg doses, at Weeks 0 and 4. No additional ORKA-001 dosing occurred through Week 28, yet skin clearance continued to improve.
PASI 100 Reached 71.4% at Week 28
EVERLAST-A is a randomized, double-blind, placebo-controlled Phase 2a study evaluating the safety, efficacy, and pharmacokinetics of ORKA-001. The trial enrolled 84 patients with moderate-to-severe plaque psoriasis across 26 sites in the United States and Canada.
Patients were randomized 3:1 to receive 600 mg of ORKA-001 or matching placebo at Weeks 0 and 4. Among the 63 patients initially treated with ORKA-001, 63.5% achieved complete skin clearance, defined as PASI 100, at Week 16.
Responses continued to strengthen by Week 28. PASI 100 increased to 71.4% (45/63), while PASI 90 reached 87.3% (55/63). IGA 0/1, indicating clear or almost clear skin, was maintained in 84.1% (53/63) of patients.
The placebo crossover group showed a similar response pattern after receiving ORKA-001 at Weeks 16 and 20. By Week 28, 40.0% (8/20) achieved PASI 100, compared with 42.9% (27/63) among patients in the original ORKA-001 group at the corresponding 12-week post-dose timepoint.
Safety Remained Consistent Through Week 28
ORKA-001 maintained a favorable tolerability profile through Week 28, with findings consistent with the established IL-23p19 class.
Between Weeks 16 and 28, upper respiratory tract infection was the only treatment-emergent adverse event reported in at least 5% of ORKA-001-treated patients, occurring in 8% (7/83). Two serious adverse events were reported: a tibial fracture and prostate adenocarcinoma in a patient who had elevated prostate-specific antigen at baseline. Neither event was considered related to treatment.
No injection-site reactions were reported, and anti-drug antibodies have not shown an observed effect on safety, efficacy, or pharmacokinetics.
Week 52 Data Expected in December 2026
The continued increase in PASI 100 after the last scheduled dose is the key finding from the Week 28 analysis. Bruce Strober, MD, PhD, lead investigator for EVERLAST-A, noted that the continued rise in complete skin clearance over time supports further investigation of ORKA-001 as a potential infrequently dosed therapy.
The study will continue through Week 52 to evaluate durability, maintenance dosing, and longer-term safety. Oruka expects to report 52-week EVERLAST-A data for all patients in December 2026.
The company is also advancing EVERLAST-B, a Phase 2b study of ORKA-001, with 16-week data expected in the fourth quarter of 2026. These datasets will clarify whether the prolonged response observed after two induction doses can translate into a sustainable dosing strategy in larger clinical development.
Reference
Oruka Therapeutics Announces Positive Week 28 Data for ORKA-001 from the Ongoing EVERLAST-A Trial Showing Deepening of Responses Without Additional Dosing, Oruka Therapeutics, 23 September 2026
ORKA-001 Versus Placebo in Patients With Moderate-to-Severe Plaque Psoriasis (EVERLAST-A), ClinicalTrials.gov ID NCT07090330
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.