-- Nearly 90 percent of patients achieve undetectable viral load in
Phase IIa trial within 28 days of combined treatment with
standard of care
SAN FRANCISCO, Nov. 3 /PRNewswire/ -- New clinical data show
antiviral activity of TMC435, an investigational protease
inhibitor (PI) being developed by Tibotec BVBA for the treatment
of chronic hepatitis C virus (HCV) infection. Tibotec will
present findings from three TMC435 studies, including a
late-breaker poster on the proof-of-principle phase IIa trial,
OPERA-1 (TMC435-C201), at the American Association for the Study
of Liver Disease's (AASLD) Liver Meeting 2008 in San Francisco.
The current standard of care treatment for HCV infection,
pegylated interferon (Peg-IFN) combined with ribavirin (RBV), is
effective in 30 to 50 percent of patients infected with chronic
genotype 1 HCV infection, the most common type in the United
States. (1) The development of new therapies and strategies for
treating HCV, particularly the introduction of direct antivirals,
may offer patients a new option with shorter treatment duration.
TMC435 Phase IIa Study Results
In interim findings from the first 28 days of treatment for the
first cohort of fifty (50) treatment naive HCV+, genotype 1,
patients (once daily dose of 25 mg or 75 mg TMC435 versus
placebo), both doses showed dose-dependent antiviral activity.
TMC435 was administered in combination with PegIFNalpha-2a/RBV
(triple therapy) for 28 days or as monotherapy for seven days
and, thereafter, in combination with PegIFNalpha-2a/RBV (triple
therapy) for three weeks. There were neither serious adverse
events, nor grade 3 or 4 adverse events, related to TMC435 or any
safety-related treatment discontinuations during this 28 day
The most common adverse events associated with TMC435 were
nausea, diarrhea, and headache. There were no clinically relevant
changes in laboratory parameters, ECGs, or vital signs.
Steady-state plasma trough levels of TMC435 25 mg and 75 mg
represented ~10 and >30-fold excess above the HCV replicon EC50
Mean reductions of HCV RNA from baseline to day seven with TMC435
alone and in triple therapy were 2.63 and 3.47 log10 IU/mL,
respectively, in the 25 mg arm, and 3.43 and 4.55 log10 IU/mL in
the 75 mg arm. In the 75 mg four-week triple therapy arm, no
viral breakthrough was observed; 9/9 patients achieved HCV RNA
below lower limit of quantification (<25 IU/mL) and 8/9 patients
achieved undetectable HCV RNA (<10 IU/mL) at day 28 (RVR=89
"These data provide important information about an emerging new
approach to treating HCV," said Professor and Chairman Michael
Manns, Hannover Medical School, Germany. "The discovery and
development of new treatments is critical to improving the
standard of care for the millions of people living with this
As a global virology leader committed to patient care, Tibotec
uses innovative science and expertise to research, develop, and
manufacture, drugs for medical conditions with an unmet need. The
company has successfully launched two antiviral medications for
the treatment of HIV and is now building a portfolio of novel
antiviral therapies for HCV with the goal of becoming a prominent
leader in the treatment of this infectious disease.
TMC435 was discovered through a drug discovery collaboration
between Medivir and Tibotec. Tibotec has the right to develop and
commercialize the compound throughout the world, excluding the
Nordic countries. In addition to TMC435, Tibotec has another PI
in phase III development for the treatment of chronic HCV
"Tibotec is committed to evaluating the safety and efficacy of
TMC435 in clinical studies to determine its potential use in
people with HCV," said Roger Pomerantz, M.D., president of
Tibotec Research and Development. "This is an important step in
our mission of addressing treatment challenges of infectious
diseases, including HCV, HIV and tuberculosis."
About the Phase IIa Study
Investigators in five European countries assessed the antiviral
activity, safety, and pharmacokinetics of two once-daily regimens
of TMC435 (25 mg or 75 mg TMC435 versus placebo) in fifty HCV
genotype 1 treatment-naive patients in an ongoing double-blind,
placebo-controlled phase IIa trial. Patients were randomized to
receive either seven days of monotherapy with TMC435 or placebo
followed by 21 days of triple therapy with TMC435 or placebo,
plus PegIFNalpha-2a (180 micrograms once weekly) and RBV
(1000-1200 mg daily); or, 28 days of triple therapy with TMC435
or placebo, plus PegIFNalpha-2a and RBV. After day 28, patients
continue on PegIFNalpha-2a/RBV alone for a total of 24 or 48
weeks at the discretion of the investigator.
TMC435 data from other studies will also be presented at the
AASLD Liver Meeting.
According to the Centers for Disease Control and Prevention
(CDC), about 3.2 million people in the United States are infected
with chronic HCV and 19,000 people are newly infected each year.
(4) Chronic infection with HCV can lead to cirrhosis and liver
cancer, and is the most common cause of liver transplant in the
United States. (5)
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development
company. The company's main research and development facilities
are in Mechelen, Belgium with offices in Yardley, Pa. and Cork,
Ireland. Tibotec is dedicated to the discovery and development of
innovative HIV/AIDS and hepatitis C drugs, and anti-infectives
for diseases of high unmet medical need.
Forward Looking Statement
This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995.
These statements are based on current expectations of future
events. If underlying assumptions prove inaccurate or unknown
risks or uncertainties materialize, actual results could vary
materially from Tibotec BVBA's expectations and projections.
Risks and uncertainties include general industry conditions and
competition; economic conditions, such as interest rate and
currency exchange rate fluctuations; technological advances and
patents attained by competitors; challenges inherent in new
product development, including obtaining regulatory approvals;
domestic and foreign health care reforms and governmental laws
and regulations; and trends toward health care cost containment.
A further list and description of these risks, uncertainties and
other factors can be found in Exhibit 99 of Johnson & Johnson's
Annual Report on Form 10-K for the fiscal year ended December 31,
2006. Copies of this Form 10-K, as well as subsequent filings,
are available online at www.sec.gov, www.jnj.com or on request
from Tibotec BVBA or Johnson & Johnson. Tibotec BVBA does not
undertake to update any forward-looking statements as a result of
new information or future events or developments.
Tibotec is a member of the Johnson & Johnson family of companies.
(1)Centers for Disease Control and Prevention (CDC).
Recommendations for Prevention and Control of Hepatitis C Virus
(HCV) Infection and HCV-Related Chronic Disease. 1998.
(2)Relapse to prior therapy is the most important factor for the
retreatment response in patients with chronic hepatitis C virus
infection. Liver Int. 2007 Sep;27(7):954-9. Sagir A, Heintges T,
Akyazi Z, Oette M, Erhardt A, Haussinger D. Klinik fur
Gastroenterologie, Hepatologie und Infektiologie,
Universitatsklinik Dusseldorf, Dusseldorf, Germany.
(3)Antiviral Research. Volume 71, Issues 2-3, September 2006,
Pages 363-371. Special Issue To Honour Professor Erik De Clercq
(4)Centers for Disease Control and Prevention (CDC). FAQs for
Health Professionals. Revised July 2008.
(5)Risk factors for hepatitis C recurrence after liver
transplantation. J Viral Hepat. 2007 Nov;14 Suppl 1:89-96.
Roche B, Samuel D. Assistance Publique-Hopitaux de Paris,
Hôpital Paul Brousse
Source: Tibotec BVBA
CONTACT: Karen Manson, +32 (479) 89 47 99, for Tibotec BVBA