Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a Potent, Multi-Genotypic Protease Inhibitor for the Treatment of Hepatitis C
IDX320 pharmacokinetic data in healthy volunteers suggest potential for once-daily dosing in HCV-infected patients - Triple combinations of direct-acting antiviral agents demonstrate strong in vitro synergy against hepatitis C virus (HCV) - Data were presented in three posters at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL)
CAMBRIDGE, Mass., April 16 /PRNewswire-FirstCall/ -- Idenix
Pharmaceuticals, Inc. (NASDAQ:IDIX) , a biopharmaceutical company
engaged in the discovery and development of drugs for the treatment
of human viral diseases, today reported promising in vitro data for
IDX320, an HCV protease inhibitor, demonstrating potent and
selective antiviral activity in multiple genotypes, or strains, of
the virus. The favorable pharmacokinetic profile defined in
preclinical studies was confirmed by interim Phase I clinical data
in healthy volunteers. Additional data presented demonstrated that
a combination of three Idenix drug candidates, including IDX320,
with different mechanisms of action produced strong synergy in
vitro. These data support the evaluation of direct-acting antiviral
(DAA) combination regimens for the treatment of HCV.
"We are excited about the preclinical and first-in-man data
presented today from the IDX320 program. With the in vitro potency
and favorable pharmacokinetic profile seen to date combined with
the potential for once-daily dosing and multi-genotypic coverage,
we believe IDX320 could offer improvements over other protease
inhibitors currently in development," said David Standring, Ph.D.,
Idenix's executive vice president, biology. "The Phase I single and
multiple ascending dose clinical study in healthy volunteers is now
complete, and we look forward to advancing IDX320 into a three-day
proof-of-concept study expected to begin in the second
quarter."
"The in vitro combination data presented today continue to
support our belief that the future of HCV treatment will be a
combination of direct-acting antivirals from different drug
classes. We are pursuing a drug development strategy to achieve
that goal," said Jean-Pierre Sommadossi, Ph.D., chief executive
officer of Idenix.
IDX320 is a potent inhibitor of NS3/4A proteases from genotypes
1a, 1b, 2a and 4a (IC(50) values from 0.8 to 1.9 nM), as well as
from genotype 3a (IC(50)=23 nM). IDX320 did not inhibit nine tested
cellular proteases (IC(50) > 10 micromolars) in vitro,
suggesting high selectivity. IDX320 bound tightly to the HCV
protease enzyme with a long dissociation half-life (> 9 hours).
The signature mutation observed in vitro was D168V, consistent with
other macrocyclic inhibitors. This mutation had reduced replication
fitness and was susceptible to treatment with interferon as well as
other classes of DAAs. Additionally, IDX320 retained activity
against mutations that produce resistance to other protease
inhibitors in clinical development. (Lallos, et al, "In Vitro
Antiviral Activity of IDX320, a Novel and Potent Macrocyclic HCV
Protease Inhibitor", Poster #768.)
After single 2 mg/kg oral doses of IDX320 in two animal species,
favorable bioavailability and a long plasma half-life were
observed, with substantial plasma concentrations 24 hours post
dose. These preclinical data were confirmed in orally-dosed healthy
volunteers (n=6) receiving a single 200 mg tablet. Further, no
significant in vitro inhibition of human drug metabolizing enzymes,
CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug
interactions in patients. (Good, et al, "Preclinical
Pharmacokinetic Profile of IDX320, a Novel and Potent HCV Protease
Inhibitor", Poster #750).
Double and triple combination in vitro studies of Idenix's HCV
direct-acting antiviral drug candidates from different HCV drug
classes, including IDX184 (a nucleotide inhibitor), IDX320 (a
protease inhibitor), IDX375 (a non-nucleoside inhibitor) and a
prototype Idenix NS5A inhibitor, were reported. Data demonstrated
that double combinations (IDX320 with IDX184, IDX375 or NS5A
inhibitor) resulted in additive to mildly synergistic effects after
3 days of treatment in vitro. Furthermore, triple combinations,
especially those including agents from three different HCV drug
classes (IDX184/IDX320/IDX375 or IDX184/IDX320/NS5A inhibitor),
demonstrated the strongest synergy in vitro. Similar results were
observed over 14-days of treatment with no evidence of viral
breakthrough or cellular cytotoxicity. (La Colla, et al, "A Triple
Combination of Direct-Acting Antiviral Agents Demonstrates Robust
Anti-HCV Activity In Vitro", Poster #769.)
About HCV
Hepatitis C virus is a common blood-borne pathogen infecting
three to four million people worldwide annually. Currently, an
estimated 170 million people are infected worldwide, representing a
nearly 5-fold greater prevalence than human immunodeficiency
virus.(1)
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge,
Massachusetts, is a biopharmaceutical company engaged in the
discovery and development of drugs for the treatment of human viral
diseases. Idenix's current focus is on the treatment of infections
caused by hepatitis C virus. For further information about Idenix,
please refer to www.idenix.com.
Forward-looking Statements
This press release contains "forward-looking statements" for
purposes of the safe harbor provisions of The Private Securities
Litigation Reform Act of 1995, including but not limited to the
statements regarding the company's future business and financial
performance. For this purpose, any statements contained herein that
are not statements of historical fact may be deemed forward-looking
statements. Without limiting the foregoing, the words "expect,"
"plans," "anticipates," "will," "expects," "goal," "estimates,"
"projects," "would," "could," "targets," and similar expressions
are also intended to identify forward-looking statements, as are
expressed or implied statements with respect to the company's
clinical development programs or commercialization activities in
hepatitis C, or any potential pipeline candidates, including any
expressed or implied statements regarding the efficacy and safety
of IDX320, the likelihood and success of any future clinical trials
involving IDX320 or successful development of novel combinations of
direct-acting antivirals for the treatment of hepatitis C. Actual
results may differ materially from those indicated by such
forward-looking statements as a result of risks and uncertainties,
including but not limited to the following: there can be no
guarantees that the company will advance any clinical product
candidate or other component of its potential pipeline to the
clinic, to the regulatory process or to commercialization;
management's expectations could be affected by unexpected
regulatory actions or delays; uncertainties relating to, or
unsuccessful results of, clinical trials, including additional data
relating to the ongoing clinical trials evaluating its product
candidates; the company's ability to obtain additional funding
required to conduct its research, development and commercialization
activities; the company's dependence on its collaborations with
Novartis Pharma AG and GlaxoSmithKline; changes in the company's
business plan or objectives; the ability of the company to attract
and retain qualified personnel; competition in general; and the
company's ability to obtain, maintain and enforce patent and other
intellectual property protection for its product candidates and its
discoveries. Such forward-looking statements involve known and
unknown risks, uncertainties and other factors that may cause
actual results to be materially different from any future results,
performance or achievements expressed or implied by such
statements. These and other risks which may impact management's
expectations are described in greater detail under the heading
"Risk Factors" in the company's annual report on Form 10-K for the
year ended December 31, 2009, as filed with the Securities and
Exchange Commission (SEC) and in any subsequent periodic or current
report that the company files with the SEC.
All forward-looking statements reflect the company's estimates
only as of the date of this release (unless another date is
indicated) and should not be relied upon as reflecting the
company's views, expectations or beliefs at any date subsequent to
the date of this release. While Idenix may elect to update these
forward-looking statements at some point in the future, it
specifically disclaims any obligation to do so, even if the
company's estimates change.
(1.) Lavanchy (2009) Liver International. 29(s1):74-81. Idenix Pharmaceuticals Contact: Teri Dahlman: 617-995-9905
Source: Idenix Pharmaceuticals, Inc.
CONTACT: Teri Dahlman, Idenix Pharmaceuticals,
+1-617-995-9905
Web Site: http://www.idenix.com/
Posted: April 2010
