Points to Consider for Clinical Efficacy Evaluation of Drugs for Palmoplantar Pustulosis in Japan

1. Background and Purpose

The Points to Consider for Clinical Efficacy Evaluation of Drugs for Palmoplantar Pustulosis (Early Consideration) is an administrative notice issued by the Pharmaceuticals and Medical Devices Agency (PMDA) on January 23, 2025 to share the current review perspective on evaluating clinical efficacy in PPP drug development. PPP is a chronic skin disease characterized by recurrent, aseptic pustules on the palms and soles and, in Japan, may be associated with focal infection and smoking history, with pathological differences compared to Western definitions of palmoplantar psoriasis.

2. Disease Characteristics and Assessment

2.1 Palmoplantar Pustulosis Overview

PPP presents with recurrent sterile pustules primarily affecting palms and soles. In Japan, clinical features and pathogenesis differ from Western concepts of localized pustular psoriasis, reflecting distinct clinical practice considerations and disease characteristics.

2.2 Key Clinical Endpoints

The guidance highlights several efficacy endpoints used in regulatory submissions:

• PPP Area and Severity Index (PPPASI) total score change from baseline at a specified week (e.g., Week 16) has been accepted as a primary efficacy endpoint in submissions. However, the PMDA notes that a consensus on the least clinically meaningful change in PPPASI has not yet been established.
• The percentage of patients achieving a pre-specified PPPASI improvement (such as PPPASI 50 achievement rate) is important for interpreting clinical effect. The PMDA views these responder rates as useful secondary efficacy measures.
• Quality of life (QOL) assessment such as Dermatology Life Quality Index (DLQI) should be included as a secondary endpoint to complement skin lesion assessment.

3. Timing of Efficacy Evaluation

PPP symptoms often fluctuate, and the onset of drug effect—especially for biologics—may be slow. Therefore, the PMDA suggests reviewing not only early endpoints such as Week 16 PPPASI change but also longer-term efficacy such as evaluation at Week 24 or Week 52 to capture sustained treatment effects.

4. Considerations for Future Endpoints

The PMDA acknowledges that higher thresholds of response (e.g., PPPASI 75 achievement) may be desirable from a clinical practice perspective and could be considered in future evaluations, although current guidance focuses on PPPASI total score.

5. Comprehensive Evaluation

While traditional skin lesion severity scores like PPPASI are central to primary efficacy assessment, a comprehensive evaluation that integrates responder rates and QOL measures such as DLQI provides a broader understanding of clinical benefit. This is particularly pertinent for diseases like PPP that substantially impact patient daily living and well-being.

Summary

In summary, the PMDA’s Early Consideration on efficacy evaluation for PPP drugs recommends use of PPPASI total score as a core metric, supported by responder rates and QOL assessments, and suggests evaluating outcomes at multiple time points to reflect disease characteristics and treatment dynamics. Consensus on clinically meaningful changes and future refinement of endpoints remain areas for ongoing scientific discussion.