ORKA-001 Achieves Complete Skin Clearance in Nearly 2/3 of Psoriasis Patients at Week 16

Oruka Therapeutics has reported positive interim results from the EVERLAST-A phase 2a trial of ORKA-001, a novel half-life extended IL-23 monoclonal antibody, in adults with moderate to severe plaque psoriasis.¹ The data, announced April 2026, showed complete skin clearance rates at week 16 that the company says numerically exceed those of all currently approved IL-23 inhibitors.

“It is really exciting to see the phase 2a data from ORKA-001 showing remarkable, field-moving achievement of 63.5% PASI-100 in just 16 weeks,” said Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine, Dermatology Times’ editor in chief. “This level of efficacy, if repeated in phase 3 trials and combined with safety, could redefine our clinical algorithm for treating moderate to severe psoriasis and do it in fewer doses per year. A huge win for psoriasis patients.”

Trial Design

EVERLAST-A (NCT07290569) is a randomized, double-blind, placebo-controlled study enrolling patients at 26 sites across the United States and Canada. A total of 84 participants were randomized 3:1 to receive ORKA-001 600 mg or matching placebo at weeks 0 and 4. Baseline characteristics were consistent with those reported in recent moderate to severe psoriasis trials.

Efficacy Results

The primary endpoint — PASI 100 at week 16, representing complete skin clearance — was achieved by 63.5% of ORKA-001-treated participants (40 of 63 patients). Identical rates were observed for IGA 0. Among secondary endpoints, PASI 90 was reached by 83% of the treatment group at week 16, and IGA 0/1 by 84%. In the placebo arm, one of 21 participants met each of these thresholds at week 16, consistent with historical placebo response rates. All efficacy data were calculated using non-responder imputation.

In a cross-trial comparison, the PASI 100 and PASI 90 rates observed with ORKA-001 appear to be numerically higher than those reported for all currently approved IL-23p19 inhibitors, and comparable to the highest clearance rates reported across any mechanism of action in plaque psoriasis, according to the company.

Safety Profile

ORKA-001 was well tolerated, with an overall adverse event profile similar to placebo. No serious treatment-emergent adverse events (TEAEs) were reported in the active treatment group; the one severe TEAE in the trial occurred in the placebo arm. TEAEs were mostly mild, with an incidence rate of 51% in the ORKA-001 group versus 57% with placebo. Upper respiratory tract infection was the only TEAE occurring in 5% or more of participants in either group, at 19% versus 14%, respectively. No injection site reactions were observed.

Pharmacokinetics and Pharmacodynamics

Updated PK and PD data from a companion phase 1 trial (NCT06698939) continue to support the potential for markedly extended dosing intervals.² Following a single 600 mg dose, drug concentrations remained above effective trough levels for a full year, with sustained suppression of IL-23 pathway signaling throughout that period. Anti-drug antibody development has not affected PK in either the phase 1 or EVERLAST-A cohorts.

The half-life extension strategy underlying ORKA-001's design is central to the program's differentiation. If efficacy at this level can be maintained with once- or twice-yearly dosing — rather than the more frequent administration required by currently approved agents — the treatment burden for patients with chronic psoriasis could be substantially reduced.

Looking Ahead

Bruce Strober, MD, PhD, clinical professor of dermatology at Yale University School of Medicine and lead investigator for EVERLAST-A, noted that if the efficacy and safety profile holds, the agent could become a preferred option for patients with moderate to severe disease.

Oruka plans to report longer-term EVERLAST-A data in the second half of 2026, including week 28 efficacy for the full cohort and 52-week follow-up for a subset. The company is also advancing EVERLAST-B, a phase 2b trial, with data anticipated 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. News release. Oruka Therapeutics. Published April 27, 2026. Accessed April 27, 2026. https://ir.orukatx.com/news-releases/news-release-details/oruka-therapeutics-announces-positive-week-16-data-orka-001
2. Oruka Therapeutics announces positive interim phase 1 results for ORKA-001. News release. Oruka Therapeutics. Published September 17, 2025. Accessed April 27, 2026. https://ir.orukatx.com/news-releases/news-release-details/oruka-therapeutics-announces-positive-interim-phase-1-results