Cenicriviroc Significantly Improved Fibrosis without Worsening of NASH at One Year
The abstract entitled "Cenicriviroc versus placebo for the treatment of
non-alcoholic steatohepatitis with liver fibrosis: Results from the Year
1 primary analysis of the Phase 2b CENTAUR study," will be presented by
"I am excited to be presenting data from the CENTAUR study, showing that
in the treated population CVC was well tolerated and resulted in twice
as many patients achieving at least a one-stage improvement in fibrosis
with no worsening of steatohepatitis compared to placebo, after only one
year of treatment," said
Cenicriviroc (CVC), an oral chemokine receptor CCR2/5 antagonist, has potent anti-inflammatory and antifibrotic activity in animal models of acute and chronic liver diseases. Its efficacy and safety as a treatment for NASH and liver fibrosis are being evaluated in adults at increased risk of progression to cirrhosis.
In the intent-to-treat (ITT) population, CVC was well tolerated and resulted in twice as many subjects achieving one stage or greater improvement in fibrosis and no worsening of steatohepatitis compared to placebo, after only one year of treatment (p=0.023). Importantly, greater treatment benefits were observed in subjects with higher NASH disease activity and fibrosis stage and thus at risk of progression. Improvement in fibrosis by two stages was observed in 11 subjects (8 CVC; 3 placebo). Seven subjects progressed to cirrhosis (2 CVC; 5 placebo). A similar proportion of patients treated with CVC compared to placebo achieved the non-alcoholic fatty liver disease activity score (NAS) and resolution of steatohepatitis endpoints. Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and fibrinogen levels, all markers associated with systemic inflammation, were significantly decreased with CVC compared to placebo.
The most common drug-related, treatment-emergent adverse events of Grade 2 or higher severity occurring in 2 percent or more of subjects were: fatigue (2.8%) and diarrhea (2.1%) for CVC and headache (3.5%) for placebo. There were no notable differences in laboratory abnormalities or premature discontinuations between CVC and placebo.
CENTAUR primary and key secondary efficacy endpoints (ITT; missing Year 1 biopsy = non response; logistic regression analysis)
CVC 150 mg
Primary endpoint: ≥2-Point improvement in NAS (with ≥1-point reduction in lobular inflammation or hepatocellular ballooning) and no worsening of fibrosis, n (%)
|23 (16%)||27 (19%)||
|Key secondary endpoint (1): Complete resolution of Steatohepatitis and no worsening of fibrosis, n (%)||11 (8%)||8 (6%)||
|Key secondary endpoint (2): Improvement in fibrosis by ≥1 stage (NASH CRN system) and no worsening of steatohepatitis, n (%)||29 (20%)||15 (10%)||
|Subgroup analyses for fibrosis improvement (key secondary endpoint 2) by baseline|
|NAS ≥5||21/89 (24%)||9/94 (10%)||
|Hepatocellular ballooning grade ≥2||18/64 (28%)||6/69 (9%)||
|Fibrosis stage 1||6/44 (14%)||2/42 (5%)||
|Fibrosis stages 2 and 3||23/82 (28%)||13/84 (16%)||
CENTAUR Trial Design
CENTAUR is a Phase 2b, randomized, double-blind, placebo-controlled,
ongoing 2-year multinational study of 289 subjects with a primary
analysis at Year 1. Subjects with histologically defined NASH (NAS ≥4),
liver fibrosis (stages 1-3 NASH CRN), and diabetes or metabolic syndrome
The trial participants were 53 percent female with a mean BMI of 34 kg/m2 (standard deviation: 6.5). The study population had advanced disease: 52 percent of patients were diagnosed with diabetes, 72 percent were diagnosed with the metabolic syndrome, 74 percent had a NAS of 5 or greater, and 67 percent had liver fibrosis of Stage 2-3.
About Cenicriviroc (CVC)
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. Because of this unique mechanism of action, targeting two of the main engines driving NASH, CVC has the potential to play a differentiated role in the management of NASH and may form the cornerstone of NASH combination treatment strategies, both as a single agent and in combination with other agents targeting metabolic pathways. CVC has been granted Fast Track status in patients with NASH and liver fibrosis, the patient population at highest risk of progression to cirrhosis.
The safety and efficacy of CVC for NASH with liver fibrosis is being
investigated in the CENTAUR study (NCT02217475).
CENTAUR is a Phase 2b multinational, randomized, double-blind study
comparing CVC to placebo in 289 adults with NASH and liver fibrosis. In
In addition to CENTAUR, CVC is also being evaluated in the PERSEUS study (identifier NCT02653625), a Phase 2 proof-of-concept study of CVC in patients with primary sclerosing cholangitis, a rare inflammatory liver disease.
About Non-Alcoholic Steatohepatitis (NASH)
NASH is a severe type of non-alcoholic fatty liver disease (NAFLD), which is characterized by the accumulation of fat in the liver with no other apparent causes. NASH occurs when the accumulation of liver fat is accompanied by inflammation and cellular damage. The inflammation can lead to fibrosis (scarring) of the liver and eventually progress to cirrhosis, portal hypertension, liver cancer, and eventual liver failure.
NASH is an emerging health crisis impacting 3 percent to 5 percent of
Tobira is a clinical-stage biopharmaceutical company focused on the development and commercialization of therapies for non-alcoholic steatohepatitis (NASH) and other liver diseases. The company's lead product candidate, cenicriviroc (CVC), is a first-in-class immunomodulator and dual inhibitor of CCR2 and CCR5 in late-stage development for the treatment of NASH, a serious liver disease that can progress to cirrhosis, liver cancer and liver failure. CVC is also being investigated to address primary sclerosing cholangitis (PSC), a disease which causes inflammation and scarring of the bile ducts, eventually leading to serious liver damage. Tobira's pipeline also includes evogliptin, a selective DPP-4 inhibitor, which it is developing for NASH in combination with CVC. Learn more about Tobira at www.tobiratx.com.
Tobira® is a registered trademark owned by
Forward Looking Statements
This release contains forward-looking statements made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform Act
of 1995. Forward-looking statements reflect management's current
knowledge, assumptions, judgment and expectations regarding future
performance or events. Although management believes that the
expectations reflected in such statements are reasonable, they give no
assurance that such expectations will prove to be correct and you should
be aware that actual results could differ materially from those
contained in the forward-looking statements. Forward-looking statements
are subject to a number of risks and uncertainties including, but not
limited to, the company's clinical development of cenicriviroc (CVC) and
evogliptin (EVO); the potential timing and outcomes of clinical studies
of Tobira's product candidates undertaken now or in the future; the
ability of the company to timely source adequate supply of its
development products from third party manufacturers on whom the company
depends; the company's limited cash reserves and its ability to obtain
additional capital on acceptable terms, or at all; the company's ability
to successfully progress, partner or complete further development of its
programs; the uncertainties inherent in clinical testing; the timing,
cost and uncertainty of obtaining regulatory approvals; the company's
ability to protect its intellectual property; competition; changes in
the regulatory landscape or the imposition of regulations that affect
the company's products; and other factors listed under "Risk Factors" in
the company's other filings with the
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