Comparative Analysis of Patient-Reported Outcomes (PROs) in Asthma Biologic Late-Phase Studies and Approved Labels: Implications for Entry and Product Differentiation
Author(s)
Jane Wells, BSc, MSc1, Rachel Reingold, MSc2.
1Patient Informed Development and Health Value Translation, Sanofi, Reading, United Kingdom, 2Global Labelling, Sanofi, Toronto, ON, Canada.
1Patient Informed Development and Health Value Translation, Sanofi, Reading, United Kingdom, 2Global Labelling, Sanofi, Toronto, ON, Canada.
OBJECTIVES: To assess the landscape of patient-reported outcome (PRO) label claims among approved and late phase asthma biologics to support understanding of entry endpoints and illustrate areas for product differentiation. This analysis aims to inform endpoint selection for future clinical development and labelling.
METHODS: A review of FDA and EMA labels, regulatory feedback, health authority reviews, and pivotal trial designs was conducted for approved asthma biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) and trial designs for late phase studies (depemokimab, dexpremispexole) in May 2025. PRO endpoints were assessed for inclusion in trials, placement in statistical hierarchies, and presence and characteristics of corresponding text in product labeling.
RESULTS: All biologics included PROs in trials though the nature of claims varied. The Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) were the most consistently accepted measures, with EMA labels favouring change from baseline analysis, often with associated p-values, while FDA labels more commonly included responder analyses, without p-values. The responder definitions (ACQ score change ≥-0.5 and AQLQ score change ≥0.5) were consistent across labels. Claims of early and sustained improvement were on EMA labels for tezepelumab, dupilumab, and reslizumab, but were absent from FDA labels. Symptom diary endpoints were tested in all trials but was only accepted on EMA labels of tezepelumab and benralizumab. Regulatory feedback emphasized that labelling endpoints should be pre-specified, multiplicity-controlled, and clinically meaningful. Endpoints outside statistical hierarchy were less likely to result in label claims, even when statistically significant.
CONCLUSIONS: ACQ-5 and AQLQ responder and change from baseline endpoints are established entry criteria for asthma biologics, with regulatory precedent supporting their inclusion. Symptom diary endpoints and other novel endpoints addressing patient-prioritized outcomes offer opportunities for differentiation. This review provided cross-asset competitive and regulatory intelligence supporting strategic clinical design for best-in-class labelling.
METHODS: A review of FDA and EMA labels, regulatory feedback, health authority reviews, and pivotal trial designs was conducted for approved asthma biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) and trial designs for late phase studies (depemokimab, dexpremispexole) in May 2025. PRO endpoints were assessed for inclusion in trials, placement in statistical hierarchies, and presence and characteristics of corresponding text in product labeling.
RESULTS: All biologics included PROs in trials though the nature of claims varied. The Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) were the most consistently accepted measures, with EMA labels favouring change from baseline analysis, often with associated p-values, while FDA labels more commonly included responder analyses, without p-values. The responder definitions (ACQ score change ≥-0.5 and AQLQ score change ≥0.5) were consistent across labels. Claims of early and sustained improvement were on EMA labels for tezepelumab, dupilumab, and reslizumab, but were absent from FDA labels. Symptom diary endpoints were tested in all trials but was only accepted on EMA labels of tezepelumab and benralizumab. Regulatory feedback emphasized that labelling endpoints should be pre-specified, multiplicity-controlled, and clinically meaningful. Endpoints outside statistical hierarchy were less likely to result in label claims, even when statistically significant.
CONCLUSIONS: ACQ-5 and AQLQ responder and change from baseline endpoints are established entry criteria for asthma biologics, with regulatory precedent supporting their inclusion. Symptom diary endpoints and other novel endpoints addressing patient-prioritized outcomes offer opportunities for differentiation. This review provided cross-asset competitive and regulatory intelligence supporting strategic clinical design for best-in-class labelling.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO52
Topic
Clinical Outcomes, Patient-Centered Research
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
Biologics & Biosimilars, Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)