Emerging drugs for the treatment of scleroderma: a review of recent phase 2 and 3 trials

ABSTRACT

Introduction

Systemic sclerosis (SSc) has the highest case-specific mortality of all connective tissue diseases. Its underlying disease mechanism affects several organs and remains incompletely understood. Ongoing work clarifying its etiopathogenesis is helping to develop targeted therapy.

Areas covered

Several clinical trials have evaluated the safety and efficacy of agents targeting different mechanisms of this disease. This review article reviews those mechanisms and surveys four key recent phase II or III clinical trials that are contributing to the landscape of SSc therapy. The reported trials primarily focus on patients with systemic sclerosis in the early phase of disease.

Expert opinion

Traditional therapies for SSc center on immunosuppressive and cytotoxic agents. A new cadre of therapies is borne from improved understandings of SSc pathobiology and target the inflammatory-fibrotic pathways. Scleroderma trials have entered the initial phase of personalized medicine, recognizing molecular subsets that will improve upon cohort enrichment and maximize the measurable benefit of future therapies.

KEYWORDS:

• Systemic sclerosis
• emerging drugs
• phase 2
• phase 3

Declaration of interest

D Khanna has received grant support from Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer; is a consultant for Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Galapagos, Genentech/Roche, GSK, Horizon Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics; has stocks with Eicos Sciences, Inc; has a leadership/equity position as the medical lead for Scleroderma Development, CivBioPharma/Eicos Sciences, Inc.; and CMA programs: Impact PH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

D Roofeh was funded by the NIH/NIAMS T32 grant (AR007080). D Khanna was funded by  grant support from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (K24‐AR‐063129).