Breakthrough Clinical Results
Oruka Therapeutics announced that the FDA cleared its Investigational New Drug (IND) application for a Phase 2a trial (EVERLAST-A) of ORKA-001, a long-acting anti-IL-23p19 antibody, in moderate-to-severe psoriasis. The EVERLAST-A trial will evaluate the safety and efficacy of a single dose of ORKA-001 in approximately 80 patients. The primary endpoint is PASI 100 at Week 16. The study will also explore the potential for once-yearly dosing and extended off-treatment remissions. Interim Phase 1 data will be presented at the EADV Congress in September, with efficacy and response duration data from EVERLAST-A expected in the second half of 2026. ORKA-001 aims to improve upon existing IL-23 inhibitors by achieving higher exposures and potentially offering longer dosing intervals.
Key Highlights
- FDA cleared IND for Phase 2a trial (EVERLAST-A) of ORKA-001 in moderate-to-severe psoriasis.
- EVERLAST-A is designed to evaluate the safety and efficacy of a single dose of ORKA-001, with a primary endpoint of PASI 100 at Week 16.
- The study will explore the potential for once-yearly dosing and extended off-treatment remissions.
- Interim Phase 1 data will be presented at EADV in September; Phase 2a data is expected in 2H 2026.
Incidence and Prevalence
Global Epidemiology of Psoriasis: Latest Estimates
According to the World Psoriasis Day Consortium (2022), approximately 125 million people globally are affected by psoriasis, representing 2%-3% of the overall community.
Prevalence
A 2017 systematic review of worldwide literature on psoriasis epidemiology found that the prevalence in adults ranged from 0.51% to 11.43%, while in children it ranged from 0% to 1.37%. Similarly, a 2013 systematic review reported that the prevalence in children ranged from 0% (Taiwan) to 2.1% (Italy), and in adults it varied from 0.91% (United States) to 8.5% (Norway).
The prevalence data available come from only 20 countries, indicating huge geographic gaps in knowledge, especially from low- and middle-income settings. The occurrence of psoriasis varied according to age and geographic region, being more frequent in countries more distant from the equator.
A 2017 Canadian study reported the crude prevalence of psoriasis per 100,000 persons was 4666.1 (95%CI: 3985.2-5429.9) in the MS population, and 3313.5 (95%CI: 3057.4-3585.3) in the matched population.
Incidence
In children, a 2010 study found the overall age- and sex-adjusted annual incidence of pediatric psoriasis was 40.8 per 100,000 (95% confidence interval: 36.6-45.1). When restricted to dermatologist-confirmed subjects, the incidence was 33.2 per 100,000 (95% confidence interval: 29.3-37.0).
In adults, incidence varied from 78.9/100,000 person-years (United States) to 230/100,000 person-years (Italy) according to the 2013 systematic review.
The incidence of psoriasis in children increased significantly over time from 29.6 per 100,000 in 1970-1974 to 62.7 per 100,000 in 1995-1999 (P < .001).
The 2017 Canadian study found the crude incidence of psoriasis per 100,000 person-years was 466.7 (95%CI: 266.8-758.0) in the MS population, and 221.3 in the matched population (95%CI: 158.1-301.4).
Clinical Characteristics
Chronic plaque psoriasis was the most common type (73.7%), and the most commonly involved sites were the extremities (59.9%) and the scalp (46.8%).
Research Gaps
Limited data on the epidemiology of psoriasis are available globally, indicating a need for further research to fill existing gaps in understanding the epidemiology of psoriasis and trends in incidence over time.
Psoriasis is a common disease, occurring more frequently with advancing age. Prevalence estimates also varied in relation to demographic characteristics - studies confined to adults reported higher estimates compared with those involving all age groups.
Unmet Needs and Targeted Populations in Psoriasis Research (Past 3 Years)
Based on PubMed publications from the past three years, several key unmet needs and targeted populations in psoriasis research emerge:
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Improving Long-Term Outcomes and Addressing Treatment Resistance: Many patients achieve initial improvement with biologics, but maintaining long-term responses and addressing treatment resistance remain challenges. Studies focus on optimizing treatment strategies, including combination therapies, dose adjustments, and switching therapies, to achieve durable responses. Research also explores predictive markers to identify patients at risk of treatment failure and guide personalized treatment decisions.
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Holistic Patient Management: Recognizing the complex interplay of physical, psychological, and social factors in psoriasis, research emphasizes a holistic approach to patient care. Studies investigate the impact of psoriasis on quality of life, mental health, and social functioning, and explore interventions to address these aspects. There is a growing focus on shared decision-making and patient preferences in treatment selection.
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Mild-to-Moderate Psoriasis: While significant progress has been made in treating moderate-to-severe psoriasis, patients with mild-to-moderate disease often experience substantial quality-of-life impairment and unmet treatment needs. Research explores new therapies and treatment strategies specifically for this population, aiming to improve efficacy and convenience while minimizing side effects. Studies also investigate the burden of mild-to-moderate psoriasis and the impact of treatment on patient-reported outcomes.
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Specific Clinical Forms and Subpopulations: Research targets specific clinical forms of psoriasis, such as pustular and erythrodermic psoriasis, which pose unique treatment challenges. Studies also focus on specific subpopulations, including children, older adults, and patients with comorbidities, to tailor treatment approaches and address their specific needs. Research also explores the impact of psoriasis on different racial and ethnic groups.
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Cost-Effectiveness and Access to Treatment: The high cost of biologics and other advanced therapies creates barriers to access for many patients. Research evaluates the cost-effectiveness of different treatment strategies and explores ways to improve access to affordable and effective care. Studies also investigate the economic burden of psoriasis on individuals, health care systems, and society.
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Advanced Therapies and Drug Development: Research continues to explore new drug targets and therapeutic approaches for psoriasis. Studies investigate novel biologics, small molecule inhibitors, and other advanced therapies, aiming to improve efficacy, safety, and convenience. Research also focuses on developing personalized medicine approaches based on biomarkers and genetic factors.
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Comorbidities and Systemic Manifestations: Psoriasis is associated with an increased risk of various comorbidities, including psoriatic arthritis, cardiovascular disease, diabetes, and mental health disorders. Research investigates the mechanisms linking psoriasis to these comorbidities and explores strategies to prevent and manage them. Studies also focus on the systemic manifestations of psoriasis and their impact on overall health.
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Real-World Evidence and Clinical Outcomes: Studies utilize real-world data to evaluate the effectiveness and safety of psoriasis treatments in routine clinical practice. This research complements findings from randomized controlled trials and provides insights into long-term outcomes, treatment patterns, and the impact of psoriasis on patients' daily lives.
In summary, psoriasis research over the past three years has focused on improving long-term outcomes, addressing treatment resistance, promoting holistic patient management, developing new therapies for mild-to-moderate disease, targeting specific clinical forms and subpopulations, improving cost-effectiveness and access to treatment, exploring advanced therapies and drug development, investigating comorbidities and systemic manifestations, and generating real-world evidence on clinical outcomes.
Study Design Parameters
Study Design Parameters and Endpoints in Key Psoriasis Trials
Study Designs
- Qualitative studies examined patients' psychosocial coping mechanisms
- Phenomenology models explored lived experiences
- Semi-structured interviews and content analysis described subjective realities
- Cross-sectional and retrospective studies assessed eosinophils in pathological specimens
- Prospective cohort studies through registries like Psocare Registry
- Phase 2b/3 randomized controlled trials with double-blind, placebo-controlled designs
- Network meta-analyses compared different treatments
Patient Populations
- First-time recipients (n = 10,539) of continuous systemic treatment
- Patients with moderate to severe plaque psoriasis (PASI score >10)
- Psoriatic arthritis patients with inadequate response to csDMARDs or TNFi
- Sample sizes ranging from 20 patients in qualitative studies to 1393 patients in tofacitinib trials
Treatment Parameters
- Duration: Typically 12 weeks for initial efficacy assessment, with extensions to 6-12 months
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Dosing regimens:
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Efalizumab: 1 mg/kg weekly
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Etanercept: 50 mg weekly
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Guselkumab: 100 mg Q4W or Q8W
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Tofacitinib: 5 mg or 10 mg BID
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Adalimumab: 40 mg subcutaneous injection every 2 weeks
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Phototherapy: 32 PUVA or UVB-NB sessions
Primary Efficacy Endpoints
- PASI scores: PASI75, PASI90, PASI100
- Static Physician Global Assessment (sPGA) scores
- American College of Rheumatology (ACR20/50) for psoriatic arthritis
- Modified van der Heijde-Sharp (vdH-S) score for joint damage
Secondary Endpoints
- Minimal Disease Activity (MDA)
- PsA Disease Activity Score
- Resolution of enthesitis and dactylitis
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Patient-reported outcomes (PROs):
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Dermatology Life Quality Index (DLQI)
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Itch Severity Score (ISS)
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Short Form-36 questionnaire (SF-36)
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EuroQOL-5D (EQ-5D)
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WHO Well-being Index (WHO-5)
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Health Assessment Questionnaire-Disability Index (HAQ-DI)
Safety Assessments
- Treatment-emergent adverse events
- Serious adverse events
- Serious infections
- Herpes zoster incidence
- Malignancy risk
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Laboratory parameters:
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Lipid profiles (LDL cholesterol, triglycerides)
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Liver enzymes (AST, ALT)
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Creatinine
Advanced Research Methods
- Single-cell RNA sequencing (scRNA-seq)
- T cell differentiation trajectories
- Machine learning for candidate gene screening
- Drug docking on potential targets
- In vivo experiments for treatment efficacy
- Immunoinfiltration analyses
Trial Design Features
- Long-term extension studies for sustained efficacy and safety
- Drug survival assessments (up to 51 months)
- Stratification by prior biologic exposure
- Early response prediction (as early as week 4-8 for some biologics)
- Treatment withdrawal and re-treatment studies
Drug used in other indications
ORKA-001 Clinical Trials Beyond Psoriasis
Based on the available information, I cannot provide specific details about ORKA-001 clinical trials for indications other than psoriasis. The context does not contain information about:
- Additional indications being investigated for ORKA-001
- Intervention models used in these trials
- Study designs for ORKA-001 in other therapeutic areas
- Treatment protocols for conditions beyond psoriasis
- Clinical trial phases for other indications
- Dosing regimens in these alternative applications
- Patient populations being studied
- Efficacy endpoints for other conditions
- Safety monitoring approaches
- Comparative studies with existing treatments
To provide accurate information about ORKA-001's development beyond psoriasis, additional clinical trial data would be needed from reliable sources such as clinical trial registries, pharmaceutical company announcements, or peer-reviewed publications.
For patients or healthcare professionals interested in ORKA-001's potential applications beyond psoriasis, consulting official clinical trial databases or contacting the developing company directly would be recommended to obtain the most current and accurate information.