Development

Oruka Therapeutics' ORKA-001 achieves 63.5% complete skin clearance in plaque psoriasis trial

Oruka Therapeutics reported Week 16 interim results from the EVERLAST-A Phase 2a trial of ORKA-001, a half-life extended IL-23p19 monoclonal antibody, in moderate-to-severe plaque psoriasis, with 63.5% of treated participants achieving complete skin clearance at the primary endpoint, the Menlo Park, California-based company said.

In the ORKA-001 psoriasis trial, 40 of 63 participants in the active arm reached PASI 100 at Week 16, with identical rates observed for IGA 0. PASI 90 was achieved by 83% of participants and IGA 0/1 by 84%, both calculated using non-responder imputation. In the placebo arm, one of 21 participants reached each of these endpoints, which the company said was consistent with historical psoriasis trial rates. On safety, 51% of ORKA-001-treated participants experienced at least one treatment-emergent adverse event compared with 57% in the placebo group; no serious treatment-emergent adverse events were reported in either arm, and the only event occurring in 5% or more of participants in either group was upper respiratory tract infection, at 19% versus 14% for placebo. There were no injection site reactions.

The EVERLAST-A trial (Oruka Therapeutics) is a randomized, double-blind, placebo-controlled Phase IIa study enrolling 84 patients with moderate-to-severe plaque psoriasis across 26 sites in the United States and Canada, randomized 3:1 to 600 mg ORKA-001 at Weeks 0 and 4 or matching placebo. The data reported represent a Week 16 interim readout; longer-term efficacy at Week 28 for all patients and 52-week follow-up for a subset are expected in the second half of 2026. The data remain interim and are drawn from a single dose cohort within an ongoing trial.

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ORKA-001 inhibits the IL-23p19 subunit, blocking IL-23 pathway signaling; updated Phase I pharmacokinetic data cited by the company indicate that drug concentrations remained above effective trough levels for one year following a single 600 mg dose, with no anti-drug antibody impact on pharmacokinetics observed. For context, guselkumab achieved PASI 90 at Week 16 in 52.9% of participants in the SPECTREM trial (NCT06039189), and risankizumab achieved PASI 90 at Week 16 in 57.3% of participants in the IMMpactful study, both as reported by their respective sponsors. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.


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