EVERLAST-A: Positive Phase 2a Data Observed for ORKA-001 in Psoriasis at Week 16

Oruka Therapeutics has announced encouraging interim findings from the EVERLAST-A phase 2a trial assessing ORKA-001 in individuals with moderate-to-severe plaque psoriasis, with clearance rates favorably comparable to currently available agents.1

This study evaluating ORKA-001, an investigational half-life extended IL-23p19 monoclonal antibody, looket at patients with plaque psoriasis, a chronic, common, inflammatory skin condition often characterized by significant itch and lesions described as sharply scaly, demarcated, and erythematous plaques.2 Patients with the disease were assessed in EVERLAST-A, a randomized, double-blind, placebo-controlled study.

“These data with ORKA-001 are highly compelling,” Bruce Strober, MD, PhD, clinical professor of dermatology at Yale University School of Medicine and lead investigator for EVERLAST-A, said in a statement.1 “If this type of efficacy and safety profile could be available with dosing once to twice per year, it would represent a major step forward for the field. I could envision this being the preferred product for any patient with moderate-to-severe psoriasis.”

The study was conducted within both the US and Canada across 26 sites. There were 84 total patients enrolled and randomized 3:1 to be treated with 600 mg of ORKA-001 at the 0 and 4-week marks, or with a matching placebo. Baseline characteristics were noted by Strober and coauthors as broadly consistent with those seen in recent moderate-to-severe psoriasis research.

At Week 16, they found 63.5% of ORKA-001-treated individuals attained the study’s primary endpoint of 100% in their Psoriasis Area and Severity Index (PASI) score, representing complete skin clearance.1 Additionally, the team identified identical data for Investigator's Global Assessment (IGA) scores of 0 0. Among key secondary endpoints, the investigators noted attainment among 83% of participants of PASI 90 IGA 0/1 among 84% at Week 16.

Among those in the placebo arm, 1 of 21 subjects met those thresholds, in line with historical placebo response rates.1 All of the study’s figures were calculated using non-responder imputation. Oruka noted these clearance rates were numerically superior to those reported for other interleukin (IL)-23p19 inhibitors in cross-trial comparisons. They also described such findings as comparable to the highest rates on record across any mechanism of action in the plaque psoriasis space.

ORKA-001’s safety profile was also found to be favorable, with no serious treatment-emergent adverse events (TEAEs) observed by Strober et al.1 They also found the single severe TEAE recorded in the study was seen in the placebo arm. Overall TEAE rates were similar between cohorts, with 51% in the ORKA-001 cohort versus 57% on placebo. The investigators noted upper respiratory tract infection the only event seen in 5% or more of those assessed in either group. No injection site reactions were found.

The phase 1 trial’s updated pharmacokinetic and pharmacodynamic data continue to support the potential for an annual dosing regimen, with ORKA-001 concentrations remaining above effective trough levels for a full year following a single 600 mg dose and sustained IL-23 pathway inhibition identified by the investigative team throughout.

In the company’s release, they noted plans to present longer-term EVERLAST-A data, including 28-week efficacy results for the full cohort and 52-week follow-up for a patient subset, in the second half of 2026. The phase 2b EVERLAST-B findings are anticipated for release in 2027.

References

1. Oruka Therapeutics Announces Positive Week 16 Data for ORKA-001 from the Ongoing EVERLAST-A Phase 2a Trial in Moderate-to-Severe Plaque Psoriasis. Oruka Therapeutics, Inc. April 27, 2026. https://ir.orukatx.com/news-releases/news-release-details/oruka-therapeutics-announces-positive-week-16-data-orka-001.

2. Kimmel GW, Lebwohl M. Psoriasis: Overview and Diagnosis. Evidence-Based Psoriasis. 2018 Jul 1:1–16. doi: 10.1007/978-3-319-90107-7_1. PMCID: PMC7122924.