Cenicriviroc Significantly Improved Fibrosis
without Worsening of NASH at One Year
Tobira Therapeutics, Inc. (NASDAQ: TBRA), a clinical-stage
biopharmaceutical company focused on developing and commercializing
therapies for non-alcoholic steatohepatitis (NASH) and other liver
diseases, today announced the acceptance of the company’s late
breaking abstract as an oral presentation at the American Academy
for the Study of Liver Diseases (AASLD) Annual Meeting (the Liver
Meeting®), being held in Boston, MA from November 11-15, 2016.
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 Arun Sanyal, M.D., Charles Caravati
Distinguished Professor and Chair, Division of Gastroenterology,
Hepatology and Nutrition at Virginia Commonwealth University on
Monday, November 14, 2016.
“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 Dr.
Sanyal. “With 9 to 15 million people impacted in the U.S., and no
currently approved treatment, NASH is an emerging health crisis,
and is predicted to become the leading cause of liver transplant in
the U.S. by 2020. These data are a critical step forward in
potentially bringing a much needed treatment option to
patients.”
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.
CENTAUR DATA
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(N=145)
Placebo(N=144)
Odds Ratio(95% CI)
p value(logisticregression)
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%)
0.8(0.44, 1.52)
0.519 Key secondary endpoint (1):
Complete resolution of Steatohepatitis and no worsening of
fibrosis, n (%) 11 (8%)
8 (6%)
1.4(0.54, 3.63)
0.494
Key secondary endpoint (2): Improvement in fibrosis by ≥1 stage
(NASH CRN system) and no worsening of steatohepatitis, n (%)
29 (20%) 15 (10%)
2.2(1.11, 4.35)
0.023 Subgroup analyses for fibrosis
improvement (key secondary endpoint 2) by baseline NAS ≥5
21/89 (24%) 9/94
(10%)
2.9(1.26, 6.78)
0.013 Hepatocellular ballooning grade
≥2 18/64 (28%)
6/69 (9%)
4.1(1.51, 11.16)
0.006 Fibrosis stage 1
6/44 (14%) 2/42 (5%)
3.2(0.60, 16.6)
0.175 Fibrosis stages 2 and 3
23/82 (28%) 13/84
(16%)
2.2(1.00, 4.69)
0.049
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 (MetS) were
randomized to receive 150 mg of CVC 150 once daily or placebo. NAS,
resolution of steatohepatitis, and fibrosis stage were assessed on
Year 1 liver biopsies. Markers of systemic inflammation,
treatment-emergent adverse events (TEAEs), and laboratory
abnormalities were also evaluated.
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 July
2016, Tobira announced that CENTAUR met the key secondary endpoint
of improvement in liver fibrosis by at least one stage with no
worsening of steatohepatitis after one year of treatment, which was
recommended by regulators as an endpoint for Phase 3 studies to
support a marketing application. The CENTAUR study continues for a
second year analysis of endpoints, which is expected in the third
quarter of 2017. The company plans to initiate a Phase 3 program in
2017.
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 the U.S. population and 2 percent to 4 percent globally,
and is the fastest growing cause of liver cancer and liver
transplant in the U.S. The increasing prevalence of NASH is
attributed to the growing obesity epidemic and the disease is often
diagnosed in patients who have diabetes, high cholesterol or high
triglycerides. There is currently no approved treatment for
NASH.
About Tobira Therapeutics
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 Tobira Therapeutics,
Inc.
©2016 Tobira Therapeutics, Inc. All Rights Reserved.
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 Securities and Exchange
Commission.
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version on businesswire.com: http://www.businesswire.com/news/home/20161020005992/en/
Tobira Investor & Media Contact:Ian Clements, Ph.D.,
+1 650-351-5013ir@tobiratx.comorBrewLife Media Contact:Kelly
Boothe, Ph.D., +1 415-946-1076kboothe@brewlife.com
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