Litifilimab (BIIB059), a promising investigational drug for cutaneous lupus erythematosus

ABSTRACT

Introduction

There are no U.S. Food and Drug Administration (FDA) approved therapies for cutaneous lupus erythematosus (CLE). Litifilimab is a monoclonal antibody against BDCA2, a plasmacytoid dendritic cell-specific antigen, currently under investigation for systemic lupus erythematosus (SLE) and CLE. The LILAC study, published in the New England Journal of Medicine, is a phase II randomized controlled trial for CLE which demonstrated superiority of Litifilimab over placebo using a skin directed outcome measure.

Areas covered

This review identifies challenges that have hindered the development of any approved treatments for CLE, recent SLE trials that include skin disease data, and the pharmacological properties of litifilimab. We review the clinical efficacy and safety of litifilimab for both SLE and CLE in the phase I and II clinical trials. This review aims to highlight the need for more CLE-specific clinical trials and examine the potential of litifilimab as the first FDA approved therapy for CLE. (Clinical trial registration: www.clinicaltrials.gov identifier is NCT02847598.)

Expert opinion

Litifilimab demonstrated efficacy in a randomized phase II clinical trial as a standalone CLE trial using validated skin-specific outcome measures, making it the first successful clinical trial for a CLE targeted therapy. If approved, litifilimab will be a pivotal change in the landscape of CLE management especially for severe and refractory disease.

KEYWORDS:

• Litifilimab
• cutaneous lupus erythematosus
• systemic lupus erythematosus
• LILAC
• Plasmacytoid dendritic cell

Article highlights

• The LILAC is a pivotal phase II trial with a positive outcome for cutaneous lupus erythematosus

• Litifilimab was well tolerated and demonstrated efficacy in a cutaneous outcome measure at 16 weeks

• Systemic lupus erythematosus (SLE) patients with skin disease are not representative of cutaneous lupus patients and outcome measures for SLE are not sufficient for capturing meaningful change in skin activity

• Trials for cutaneous lupus are needed apart from trials for systemic lupus to investigate new therapies, as no treatments have yet been approved for cutaneous lupus

• The LILAC study successfully employed a skin-directed outcome measure to capture change in disease activity

Declaration of interests

The University of Pennsylvania owns the rights to the CLASI. Dr. Werth has performed studies funded by Biogen and is a consultant with Biogen and Astra-Zeneca.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The manuscript was funded by the United States Department of Veterans Affairs Office of Research and Development (VPW) and NIH (NIAMS) R01AR071653 (VPW).