A phase 2a trial of brepocitinib for cicatricial alopecia - 03/12/24

Doi : 10.1016/j.jaad.2024.09.073

Eden David, BA ^a, Neda Shokrian, BA ^a,^b, Ester Del Duca, MD, PhD ^a,^c, Marguerite Meariman, MD ^a, Celina Dubin, MD ^a, Kelly Hawkins, BS ^a,^b, Elizabeth Andrews, MD ^a, Savina Sikand, MHA ^a, Giselle Singer, BS ^a, Barry Oemar, MD ^d, Yeriel Estrada, BS ^a, Swaroop Bose, MS ^a, Juliana Pulsinelli, BA ^a, Ping Mahling, PhD ^d, Joel Correa Da Rosa, PhD ^a, Benjamin Ungar, MD ^a, Elena Peeva, MD ^d, Emma Guttman-Yassky, MD, PhD ^a,^⁎
^a Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
^b Albert Einstein College of Medicine, New York, New York
^c Division of Dermatology, Department of Systems Medicine, Universita degli Studi di Roma Tor Vergata, Rome, Italy
^d Pfizer Inc, Cambridge, Massachusetts

^∗Correspondence to: Emma Guttman-Yassky, MD, PhD, Department of Dermatology, Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, 5 East 98th St, New York, NY 10029.Department of DermatologyLaboratory of Inflammatory Skin DiseasesIcahn School of Medicine at Mount Sinai5 East 98th StNew YorkNY10029

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 03 December 2024

Abstract

Background

Cicatricial alopecias are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and Janus kinase dysregulation has shown involvement, providing rationale for this phase 2a trial with Tyrosine kinase 2/Janus kinase 1 inhibitor brepocitinib.

Methods

Randomized, placebo-controlled phase 2a trial spanning 52 weeks. Adults (≥18 years of age) with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia diagnosis were randomized 3:1 to brepocitinib 45 mg daily or placebo for 24 weeks, after which all patients received brepocitinib for another 24 weeks, with a safety follow up 4 weeks later. Lesional scalp biopsies were collected at baseline, week 24, and week 48. Coprimary endpoints were changes in lesional expression of C-C motif chemokine ligand (CCL5), changes in lesional expression of fibrosis-related markers, and safety at week 24.

Results

Patients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 (P = .004). Enrichment analysis of a subset of fibrosis markers showed trending upregulation in placebo patients (P < .1). Brepocitinib was well tolerated and improved clinical severity scores.

Limitations

Single-dose regimen, small placebo group.

Conclusion

Brepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting coprimary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile.

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Key words : central centrifugal cicatricial alopecia, cicatricial alopecia, fibrosis, frontal fibrosing alopecia, IFNγ, JAK inhibitor, lichen planopilaris, phase 2a trial, scarring alopecia, systemic treatment, Th1

Abbreviations used : AE, CA, CCCA, CCL, CHLG, DLQI, FFA, FFASI, IFN, JAK, LPP, LPPAI, STAT, Th, TYK

Plan

Introduction

Methods

Study design and oversight

Efficacy and safety endpoints

Biomarker and clinical evaluations

Results

Patient characteristics

Primary mechanistic endpoint outcome

Primary safety outcome

Key secondary endpoint outcomes

Key secondary clinical efficacy outcomes

Correlation analysis

Discussion

	Authors David and Shokrian, and Drs Del Duca and Meariman are cofirst authors.
	Funding sources: This study was funded by Pfizer Inc.
	Patient consent: The authors attest to obtaining written patient consent for the publication of recognizable patient photographs or other identifiable material, with the understanding that this information may be publicly available.
	IRB approval status: Reviewed and approved by institutional review board of the Icahn School of Medicine at Mount Sinai (STUDY-21-00017).
	Trial registry: Dual JAK1/TYK2 Inhibitor for Cicatricial Alopecia (NCT05076006).