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PMDA Issues Early Considerations for Clinical Development of Psoriatic Arthritis (PsA) Treatments in Japan

2025.11.26

Introduction to the Early Consideration Document

According to the PMDA’s early consideration document (published 13 November 2025), Japan outlines key scientific and regulatory expectations for the clinical development of new therapies targeting Psoriatic Arthritis (PsA). As PsA is a heterogeneous inflammatory disease with relatively low prevalence in Japan, the PMDA emphasizes realistic development strategies, suitable endpoints, and the need for early dialogue with the Agency—particularly for multi-regional clinical trials (MRCTs) and pediatric development plans.

Development Strategy and the Use of MRCTs

Unlike diseases with large domestic patient populations, PsA’s prevalence in Japan is limited (≈8–13% among psoriasis patients). Consequently, conducting sufficiently powered Japan-only confirmatory trials may not be feasible.
PMDA recommends planning MRCTs from an early stage when:

• Disease characteristics and treatment environments are similar globally, and
• No major concerns regarding ethnic differences in PK/PD are expected.

If Japanese participation is difficult, sponsors are encouraged to consult PMDA early for alternative strategies.

Confirmatory Study Design Considerations

Study Design and Control Arms

PMDA states that confirmatory trials should be randomized, double-blind, and controlled.
While active-controlled trials may be possible depending on the product’s intended clinical positioning, placebo-controlled designs are generally expected.

Target Population

Two key patient groups should be distinctly considered:

• Bio-naïve patients (inadequate response to NSAIDs or csDMARDs)
• Bio-IR patients (inadequate response to biological DMARDs)

If both populations are included in a single study, PMDA expects adequate stratification and prior justification through exploratory data showing no major differences in treatment effect.

Efficacy Endpoints and Evaluation Timing

Due to heterogeneity in the clinical manifestations of PsA (joints, enthesitis, dactylitis, skin, and nails), a single comprehensive endpoint has not yet been established.
PMDA provides the following direction:

• Primary Endpoint:
  • ACR response criteria (ACR20/50/70) remain the most appropriate and widely accepted.
• Secondary Endpoints:
  • Enthesitis (e.g., LEI)、Dactylitis (e.g., LDI)、Nail psoriasis (mNAPSI)、Skin symptoms (PASI)
  • Minimal Disease Activity (MDA) should be included as an important secondary endpoint.
• Timing of Evaluation:
  • Primary assessment should be at 12–24 weeks, aligning with guideline recommendations.
  • Long-term efficacy and durability should be assessed through 52-week follow-up.

Pediatric Development Considerations

Given the extremely small number of pediatric PsA patients in Japan, local pediatric trials may be impractical.
PMDA suggests:

• Considering extrapolation based on adult PsA data and pediatric psoriasis data,
• Utilizing modeling and simulation approaches, and
• Engaging early with PMDA regarding pediatric development plans.

Conclusion

PMDA’s early considerations provide a structured framework for PsA drug development in Japan, emphasizing the selection of appropriate endpoints, the strategic use of MRCTs, and early scientific consultation. These recommendations aim to facilitate efficient development programs despite the small domestic patient population and to ensure robust evidence generation for future regulatory submissions.

References:

000277950.pdf