ORUKA (ORKA): 71% COMPLETE SKIN CLEARANCE AFTER TWO DOSES
Oruka Therapeutics ($ORKA) reported new Week 28 Phase 2a data from its EVERLAST-A study of ORKA-001 in moderate-to-severe plaque psoriasis.
The headline result:
71.4% of patients achieved complete skin clearance at Week 28 — after receiving just two doses, at Weeks 0 and 4.
What is ORKA-001?
ORKA-001 is a long-acting monoclonal antibody targeting IL-23p19, an inflammatory pathway involved in psoriasis.
IL-23 is already a validated target in psoriasis and is targeted by approved therapies including Skyrizi and Tremfya.
Oruka is developing ORKA-001 with an extended half-life, with the goal of potentially treating patients only once or twice per year.
The EVERLAST-A Study
EVERLAST-A is a Phase 2a trial involving 84 patients with moderate-to-severe plaque psoriasis.
Patients were initially randomized 3:1 to receive either:
ORKA-001 600 mg at Weeks 0 and 4
or
Placebo
After the second ORKA-001 dose at Week 4, patients received no additional ORKA-001 through Week 28.
The Results
One of the primary measures used in psoriasis trials is PASI — Psoriasis Area and Severity Index.
PASI 90 means a patient's psoriasis severity improved by at least 90%.
PASI 100 means complete skin clearance.
Week 16
PASI 100: 63.5%
PASI 90: 82.5%
Week 28
PASI 100: 71.4%
PASI 90: 87.3%
The complete-clearance rate therefore increased between Weeks 16 and 28 despite patients receiving their last dose at Week 4.
In actual patient numbers:
40 of 63 ORKA-001 patients had completely clear skin at Week 16.
By Week 28:
45 of 63 had completely clear skin.
A Second Group Produced Similar Early Results
Patients originally assigned to placebo crossed over to ORKA-001 treatment at Weeks 16 and 20.
Twelve weeks after beginning treatment:
40.0% — 8 of 20 crossover patients — achieved PASI 100.
At the comparable point following treatment in the original ORKA-001 group:
42.9% — 27 of 63 patients — had achieved PASI 100.
Why Study Treatment Duration?
Current IL-23 psoriasis therapies have demonstrated substantial efficacy but require ongoing maintenance dosing.
ORKA-001 is being engineered to remain active in the body for substantially longer.
Earlier Phase 1 pharmacokinetic data showed ORKA-001 concentrations remained above the company's estimated effective trough level for one year following a single 600 mg dose.
The clinical question is whether that long half-life can translate into sustained psoriasis control with once- or twice-yearly dosing.
Safety Through Week 28
Between Weeks 16 and 28, the only treatment-emergent adverse event reported in at least 5% of ORKA-001-treated patients was:
Upper respiratory tract infection: 8%
Two serious adverse events were reported — a tibial fracture and prostate adenocarcinoma in a patient with elevated PSA at baseline.
Oruka reported that neither was considered related to ORKA-001.
The company also reported:
No injection-site reactions
and
No observed impact from anti-drug antibodies on safety, efficacy or pharmacokinetics through Week 28.
What Comes Next?
There are three upcoming milestones for ORKA-001:
Q4 2026 — EVERLAST-B
Week 16 results are expected from the larger 187-patient Phase 2b dose-ranging study.
December 2026 — EVERLAST-A
Oruka expects to report 52-week data, providing a longer look at durability following the two-dose regimen.
1H 2027 — Phase 3
Oruka expects to begin its Phase 3 ORKA-001 program.
ORKA-001 BY THE NUMBERS
84 — patients in EVERLAST-A
2 — doses administered
Week 4 — last dose
63.5% — complete skin clearance at Week 16
71.4% — complete skin clearance at Week 28
87.3% — achieved at least 90% skin clearance at Week 28
52 weeks — next durability readout
1H 2027 — planned start of Phase 3
For now, the EVERLAST-A study is continuing to evaluate whether ORKA-001's extended half-life can translate into durable psoriasis control with substantially less frequent dosing.
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