Oruka Therapeutics announces interim results from EVERLAST-A trial

Oruka Therapeutics (ORKA) announced interim results from its EVERLAST-A Phase 2a trial of ORKA-001, a novel half-life extended IL-23p19 monoclonal antibody, in moderate-to-severe plaque psoriasis. Overall, 40 of 63 participants treated with ORKA-001 achieved the primary endpoint of PASI 100 at Week 16, representing complete skin clearance. Identical results were observed for IGA 0. Other key secondary endpoints included PASI 90 at Week 16, achieved by 83% of participants, and IGA 0/1 at Week 16, achieved by 84% of participants. One of 21 participants receiving placebo reached PASI 100, IGA 0, PASI 90, and IGA 0/1 at Week 16, in line with historical psoriasis trials. All response rates were calculated using non-responder imputation. Based on a cross-trial comparison, these data with ORKA-001 demonstrate numerically higher rates of skin clearance than all other IL-23p19 inhibitors and are comparable to the highest reported in plaque psoriasis for any mechanism of action. ORKA-001 was well tolerated with a safety profile similar to placebo and consistent with prior IL-23p19 inhibitors. There were no serious treatment-emergent adverse events and one severe TEAE, which occurred in the placebo group. Most TEAEs were mild in severity. The overall rate of TEAEs was comparable across groups, with 51% of participants treated with ORKA-001 and 57% of participants receiving placebo experiencing at least one TEAE. The only TEAE that occurred in 5% or more of subjects in either group was upper respiratory tract infection. There were no injection site reactions. Updated PK and PD data from the Phase 1 trial of ORKA-001 continue to support the potential for annual dosing. Following a single 600 mg dose, ORKA-001 concentrations remained well above effective trough levels for an entire year, with sustained inhibition of IL-23 pathway signaling observed throughout that time period. No impact of anti-drug antibodies on PK has been seen in either the Phase 1 or EVERLAST-A trials. Oruka plans to share longer-term data from EVERLAST-A, including efficacy at Week 28 for all patients and 52-week follow-up for a subset of the cohort, in the second half of 2026. The company also continues to advance the Phase 2b EVERLAST-B trial, with data expected in 2027.