Begins Proof-of-Concept Study of HCV Protease Inhibitor IDX320
Pharmaceuticals announced last week that it has started
a 3-day proof-of-concept study of its experimental hepatitis
C virus (HCV) protease inhibitor IDX320. As
previously reported, researchers presented data
at the recent EASL conference showing that IDX320 showed
good anti-HCV activity in laboratory studies and had
good pharmacokinetic and safety profiles in animals
and HCV negative volunteers. If the latest study produces
favorable results, the company expects to test IDX320
and its investigational HCV polymerase inhibitor IDX184
as a combination regimen.
is an excerpt from a recent Idenix press release describing the
drugs and the new study.
Pharmaceuticals Initiates Proof-of-Concept Study for Protease
Inhibitor IDX320 in Hepatitis C Patients
Mass. -- June 10, 2010 -- Idenix Pharmaceuticals, Inc. (Nasdaq:
IDIX), a biopharmaceutical company engaged in the discovery and
development of drugs for the treatment of human viral diseases,
today announced that it has initiated a 3-day proof-of-concept
study of IDX320, a protease inhibitor for the treatment of hepatitis
C virus (HCV) infection, under a Clinical Trial Application (CTA).
The study is evaluating IDX320 in treatment-naive hepatitis C
genotype 1-infected patients.
"The potent and multi-genotypic activity demonstrated in
vitro, as well as the favorable pharmacokinetics observed
in healthy volunteers, suggests a promising profile for further
development of IDX320," said Jean-Pierre Sommadossi, PhD,
chief executive officer of Idenix. "The landscape for combination
development in HCV is evolving quickly. Assuming favorable results
from the IDX320 proof-of-concept study, we plan to discuss with
regulatory agencies a direct-acting antiviral combination strategy
with IDX320 and IDX184, our HCV nucleotide polymerase inhibitor."
Douglas Mayers, MD, Idenix's chief medical officer commented,
"We are encouraged by the results seen to date with IDX320
and are hopeful that future clinical studies will allow us to
continue advancing this program with the ultimate goal of treating
a wide range of patients infected with HCV."
The proof-of-concept trial in HCV-infected patients is a Phase
I/II randomized, parallel-arm, double-blind, placebo-controlled
study evaluating the safety and antiviral activity of IDX320 in
treatment-naive adult patients infected with chronic hepatitis
C. The study will evaluate four doses of IDX320, ranging from
50 to 400 mg once-per-day, administered for three days. Each cohort
of the study will evaluate eight patients randomized six to IDX320
and two to placebo.
IDX320, a macrocyclic HCV protease inhibitor, is an inhibitor
of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC50 values
from 0.8 to 1.9 nM), as well as from genotype 3a (IC50=23 nM).
IDX320 did not inhibit nine tested cellular proteases (IC50 >
10 uM) in vitro, suggesting high selectivity. IDX320 bound
tightly to the HCV protease enzyme with a long dissociation half-life
(> 9 hours). 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. Comparable drug exposure was confirmed in healthy volunteers
(n=6) receiving a single 200 mg oral dose. 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.
IDX184 is a novel, liver-targeted nucleotide prodrug of 2'-methyl
guanosine monophosphate, which includes Idenix's proprietary liver-targeting
technology. This technology enables the delivery of nucleoside
monophosphate to the liver, leading to the formation of high levels
of nucleoside triphosphate, potentially maximizing drug efficacy
and limiting systemic side effects with low, once-daily dosing.
IDX184 in combination with pegylated interferon and ribavirin
has demonstrated a generally favorable safety profile and potent
antiviral activity in an ongoing Phase IIa study.
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 patients with chronic hepatitis C
For further information about Idenix, please refer to www.idenix.com.
Idenix Pharmaceuticals. Idenix Pharmaceuticals Initiates Proof-of-Concept
Study for Protease Inhibitor IDX320 in Hepatitis C Patients. Press
release. June 10, 2010.