ORION is a randomized, double-blind, placebo-controlled study exploring the metabolic effects of cenicriviroc (CVC) in obese adults (BMI greater than or equal to 30 kg/m2) with prediabetes or diabetes and suspected non-alcoholic fatty liver disease (NAFLD). The primary outcome of ORION will measure changes in insulin sensitivity in peripheral and adipose tissue over a 24-week period and will include an interim analysis at 12 weeks. Tobira plans to announce the top-line 12-week interim analysis in the second quarter of 2016 and submit results for presentation at a scientific conference.
"Completion of enrollment in this mechanistic study marks another milestone for Tobira as we explore the full potential of CVC," said Laurent Fischer, M.D., chief executive officer of Tobira. "In previous clinical and nonclinical studies, CVC has demonstrated anti-inflammatory and anti-fibrotic activity, impacting two key engines of disease progression in NASH. ORION allows us to explore CVC’s impact on insulin resistance, which plays a determining role in NASH."
In obese patients, the over-expression of CCR2 and CCR5 receptors and their ligands in fat tissue has been shown to promote both inflammation and insulin resistance. Insulin resistance is associated with the development of NAFLD and is a key driver for disease progression to its more severe form, non-alcoholic steatohepatitis (NASH), as well as other diabetes-related complications.
Details about ORION can be found at www.clinicaltrials.gov using identifier NCT02330549.
About Cenicriviroc (CVC) and Non-alcoholic Steatohepatitis (NASH)
CVC is an oral, once-daily, potent immunomodulator that blocks two chemokine receptors, CCR2 and CCR5, which are intricately involved in the inflammatory and fibrogenic pathways in NASH that cause liver damage and often lead to cirrhosis, liver cancer or liver failure. Tobira believes this novel approach will establish CVC as both a single-agent and as a cornerstone treatment in multi-therapy regimens for NASH, for which there is currently no approved drug.
CVC is currently being evaluated in Tobira’s fully enrolled global Phase 2b CENTAUR study (identifier NCT02217475) and the company expects to announce the study’s primary endpoint in the third quarter of 2016. CENTAUR is comparing CVC to placebo in 289 patients with NASH and liver fibrosis. CVC has been granted Fast Track status in NASH in patients with liver fibrosis, the patient population at highest risk of progression to cirrhosis. The CENTAUR study includes surrogate endpoints identified as suitable for registrational studies in findings of an FDA-AASLD workshop reported in Hepatology. To date, approximately 600 subjects have been dosed in completed studies with CVC, including 115 HIV infected subjects on treatment for up to 48 weeks.
NASH is an emerging health crisis impacting 3% to 5% of the U.S. population and 2% to 4% globally. It is the fastest growing cause of liver cancer and liver transplant in the U.S. due to the rise in obesity. Additionally, this population is estimated to be three to five times larger than the size of the population with hepatitis C in the U.S