Investigational drugs in phase II clinical trials for primary biliary cholangitis

ABSTRACT

Introduction: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40% of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed.

Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials.

Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.

KEYWORDS:

• Autoimmune liver disease
• bile duct disorders
• cholestasis
• pharmacotherapy

Article Highlights

• Primary biliary cholangitis is a rare chronic cholestatic liver disease that can lead to biliary fibrosis and eventually cirrhosis if untreated. The primary treatment for PBC is UDCA.

• Patients with PBC who have an inadequate response to or cannot tolerate UDCA are at higher risk of developing liver-related complications of PBC, and represent an unmet clinical need in PBC.

• Recent advanced in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents at different stages of development for treatment in PBC, including bile acid therapies, PPAR agonists, immunological agents, and stem cells.

• Large controlled clinical trials are need to determine the long-term effects of novel therapies on the clinical outcomes of PBC, but design and conduct of high quality studies is challenging.

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Declaration of interest

K. D. Lindor has served as an advisor for Intercept and Shire, and a DSMB member for Takeda. 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.

Additional information

Funding

This paper was not funded.