ORKA-001 Achieves 61% Complete Skin Clearance in Psoriasis

Oruka Therapeutics has announced positive week 16 results from the phase 2b EVERLAST-B trial evaluating ORKA-001, a half-life–extended IL-23p19 monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. The high-dose regimen achieved complete skin clearance in 61% of patients, supporting the company’s plans to advance the investigational therapy into phase 3 development in 2027.¹

EVERLAST-B is a randomized, double-blind, placebo-controlled phase 2b trial evaluating the safety, efficacy, and pharmacokinetics of ORKA-001. The study enrolled 187 patients across 36 sites in the United States, Canada, and Europe, with participants randomized 1:1:1:1 to receive ORKA-001 at 37.5 mg at week 0, 300 mg at weeks 0 and 4, 600 mg at weeks 0 and 4, or placebo.¹

High-Dose ORKA-001 Meets Primary End Point

At week 16, 61% of patients receiving the 600-mg regimen achieved a 100% improvement in Psoriasis Area and Severity Index (PASI 100), the trial’s primary end point, compared with 0% of patients receiving placebo (P < .0001).¹

Complete skin clearance increased in a dose-dependent manner. PASI 100 was achieved by 43% of patients receiving the 37.5-mg dose, 44% receiving the 300-mg regimen, and 61% receiving the 600-mg regimen, compared with 0% in the placebo group.¹

Responses across key secondary end points were also highest with the 600-mg regimen. At week 16, 86% of patients in this group achieved PASI 90, and 86% achieved an Investigator’s Global Assessment (IGA) score of 0 or 1. By comparison, PASI 90 response rates were 70% and 85% in the low- and mid-dose groups, respectively, while IGA 0/1 rates were 74% and 85%. No placebo-treated patients achieved either end point.¹

The findings closely align with results previously reported from the phase 2a EVERLAST-A trial. In that study, 63.5% of patients treated with ORKA-001 achieved PASI 100 at week 16, while 83% achieved PASI 90 and 84% achieved IGA 0/1.²

“These results suggest ORKA-001 is likely to be the most effective IL-23-targeting biologic to date,” Joel Gelfand, MD, MSCE, FAAD, James J. Leyden Professor of Dermatology and Epidemiology at the University of Pennsylvania and lead investigator for EVERLAST-B, said in a news release.¹

Gelfand added that the possibility of maintaining these responses with 1 or 2 doses annually could potentially combine skin clearance, treatment convenience, and safety for patients with moderate-to-severe psoriasis.²

Safety Findings

ORKA-001 continued to demonstrate a safety and tolerability profile consistent with the IL-23p19 class. Through week 16, 49% of all ORKA-001-treated patients experienced at least 1 treatment-emergent adverse event (TEAE), compared with 43% of patients receiving placebo.¹

In the 600-mg group, 39% of patients experienced at least 1 TEAE. The only TEAEs occurring in at least 5% of ORKA-001-treated patients were upper respiratory tract infection and headache. No dose-dependent trends in adverse events were observed, and no injection-site reactions occurred among ORKA-001-treated patients.¹

No serious or severe TEAEs occurred in the 600-mg group. Across the ORKA-001 groups, serious TEAEs were reported in 2% of patients, and none were considered treatment related.¹

Evaluating Less Frequent Maintenance Dosing

Beyond induction efficacy, EVERLAST-B is designed to evaluate whether the extended half-life of ORKA-001 can support substantially less frequent maintenance dosing.

At week 28, patients treated with ORKA-001 who have achieved PASI 100 will be rerandomized to either 600 mg ORKA-001 once yearly or placebo. Patients who have not achieved PASI 100 will receive ORKA-001 300 mg every 6 months. The study will continue through week 100 to evaluate durability of response, maintenance dosing, and long-term safety.¹

The potential for once- or twice-yearly administration could represent an important differentiating feature if the efficacy and durability observed in the EVERLAST program are maintained in longer-term and phase 3 studies.

Based on results from the EVERLAST clinical program, Oruka plans to discuss phase 3 development with regulatory authorities. Pending those discussions, the company expects to initiate phase 3 trials of the 600-mg ORKA-001 regimen in moderate-to-severe plaque psoriasis during the first half of 2027.¹

Additional data will further clarify the durability of response. Oruka expects to report 52-week EVERLAST-A results in December 2026, followed by 52-week EVERLAST-B results in the second half of 2027.¹

References

1. Oruka Therapeutics. Oruka Therapeutics announces positive week 16 results for ORKA-001 from the ongoing EVERLAST-B trial in moderate-to-severe psoriasis. Published October 26, 2026. Accessed October 26, 2026.
2. Oruka Therapeutics. Oruka Therapeutics announces positive week 16 data for ORKA-001 from the ongoing EVERLAST-A phase 2a trial in moderate-to-severe plaque psoriasis. Published April 27, 2026. Accessed October 26, 2026.