Polymerase/Protease Inhibitors in Development

Drug Name Drug Category Pharmaceutical Company Clinical Phase
GSK625433 Polymerase Inhibitor GlaxcoSmithKline Phase I
Comments: Currently recruiting patients to study the initial safety
and tolerability in healthy adults as well as anti-viral activity.
(September 04, 2007)
TMC435350 Protease Inhibitor Medivir/Tibotec Phase I
Comments: A Phase I clinical study has been initiated. (February 9,
2007)
ITMN-191
(R-7227) Protease Inhibitor InterMune Phase I
Comments: Successful preclinical toxicology and pharmcokentic
studies have been completed. On December 19, 2006 InterMune
announced the commencement of a phase I trial will begin in January
2007 enrolling 74 healthy volunteers in France. On October 16, 2006
InterMune and Roche entered into an agreement to develop and
implement InterMune's protease inhibitor pipeline including ITNM
191. In early May 2007, InterMune reported that it had completed
dosing in a Phase 1a single ascending-dose (SAD) trial of ITMN-191
in healthy subjects. No serious adverse events were reported in the
SAD trial. Preliminary safety data from the SAD trial suggests that
ITMN-191 was well tolerated and safe at the doses intended for the
Phase 1b multiple-ascending dose (MAD) trial of ITMN-191. InterMune
announced on September 4, 2007 that HCV patient recruitment will
begin in September 2007 in Europe. (September 4, 2007)
R7128 Polymerase Inhibitor Pharmasset/Roche Phase I
Comments: Pharmasset in collaboration with Roche has begun the
multiple ascending dose portion of an on-going Phase I trial in 40
HCV genotype 1 patients to assess the safety, tolerability,
pharmacokinetics and antiviral activity of multiple doses of R7128
after once-daily or twice-daily dosing for 14 days.

On September 11, 2007 preliminary data on the study was released by
Pharmasset. It was found that there was a dose-dependent anitiviral
activity across all dosing arms with the 1,500 mg twice-daily arm
achieving a great than 99% decrease in HCV RNA (viral load). It was
also reported that R7128 was generally safe and well-tolerated with
no serious adverse events or any dose reductions due to adverse
events. Based on this data, Pharmasset/Roche plan to start a 28-day
study of R7128 in combination with Pegasys that is to begin late
September 2007. (September 18, 2007)
R1626 Polymerase Inhibitor Roche Phase II
Comments: AASLD 2006: 47 patients given oral doses (500 mg, 1500mg,
3000 mg, 4500) achieved viral load reductions of 1.2, 2.6, and 3.7
log 10 in the 100 mg, 300 mg and 4500 mg doses respectively. R1626
was generally well-tolerated with increasing adverse events at the
highest dose (4500 mg). No viral resistance was found. On October
13, 2005 Roche announced the start of a phase II study with R1626 in
combination with Pegasys plus Copegus and that R1626 has been
granted Fast Track status by the FDA. (November 8, 2006)
SCH 503034 (Boceprevir) Serine Protease Inhibitor Schering Phase II
Comments: In two studies presented at AASLD 2005, 61 genotype-1
patients in a 14-day course of treatment (5 treatment arms including
1 placebo arm), showed an HCV RNA reduction with the maximum HCV
reduction of more than 2 logs in the group receiving 400 mg of
SCH503034. SCH503034 was safe and well-tolerated with no serious
adverse events. In another study, SCH503034 in combination with Peg-
Intron resulted in a decrease of more than 2 logs overall with 4 out
of 10 subjects in the 400 mg arm achieving undetectable HCV RNA.
Phase II studies with the combination of SCH503034 and Peg-Intron
are underway. In April 2006, it was announced that patient
enrollment in this trial was completed. In January 2006 the FDA
granted Fast Track Designation. (April 17, 2007)
VX 950 (telaprevir) Protease Inhibitor Vertex Phase II
Comments Vertex has initiated two large multi-international studies
(Prove 2 and Prove 3) and has begun recruitment of Gentoype 1, 2, 3
treatment naïve and treatment experienced patients..
EASL:
In the three arms that included the combination of telaprevir,
Pegasys and ribavirin, it was found that 85% of patients were
undetectable at week 12 (less than 10 IU/ml) compared to43% in the
placebo plus Pegasys and ribavirin. The side effect profile was
comparable between treatment groups. The most common reason for
treatment discontinuation in the telaprevir arms was rash (7
patients). The early rapid response in the telaprevir arms indicate
that it might be possible to shorten treatment duration from 48 to
24 weeks for genotype 1 patients. In July 2007, Vertex reported on
some of the interim 12-week post treatment data from all patients
who finished the 24 weeks of the arm C ( PROVE I clinical trials).
Of the patients in this study who had undetectable HCV RNA (less
than 10 IU/mL) at the end of treatment, less than 10% had relapsed.
(July 28, 2007)
NM283 (Valopicitabine) Polymerase Inhibitor Idenix Pharmaceuticals
Phase II
Comments:.
Study 1--Non-responder study: Results reported from EASL found that
the trial failed to meet its goal, with no patients in this
difficult to treat group responding to the treatment. Study II –
Treatment naïve study: Phase II study results were released and it
was found that 72.2% of treatment naïve patients receiving the
valopicitabine, pegylated interferon plus ribavirin triple therapy
were HCV RNA negative after12 weeks compared to 61.5% in the group
receiving pegylated interferon plus ribavirin. Idenix announced that
they will be beginning a phase IIb dosing study of valopicitabine
(200 and 400 mg dose) in combination with pegylated interferon plus
ribavirin in about 300 genotype 1 treatment naïve patients towards
the end of 2007 and are planning a phase III study of triple therapy
for 2008.
In July 2007 the FDA placed the current clinical developed on hold
after valopicitabine failed a risk/benefit analysis performed by the
FDA. Idenix's CEO stated that he is not optimistic about the future
development of valopicitabine (July 28, 2007)



Anti Liver Cancer Drugs in Development

Drug Name Drug Category Pharmaceutical Company Clinical Phase
ZIO-101 Anti-Liver Cancer (Arsenic) ZIOPHARM Oncology Phase II
Comments; On May 10, 2007, ZIOPHARM announced the dosing of the
first patient in a phase II trial for the treatment of primary liver
cancer. This study is not specific to hepatitis C-related liver
cancer. (May 29, 2007)
GV1001 (Heptovax) Anti-Liver Cancer Pharmexa
Phase II

Comments: Initiation of phase II studies has begun in France, Spain
and Germany to treat liver cancer (HCC).The trail will enroll 41
patients with advanced liver cancer using GV1001 in combination with
GM-CSF (stimulates the production of neutrophils or white blood
cells). (December 12, 2006)
PI-88 Anti-liver cancer Progen Industries
Phase II

Comments: A treatment for primary liver cancer following surgical
resection of a liver tumour. Preliminary results from the Phase II
study of patients treated with 160 mg showed a substantial delay in
tumour recurrence compared to the patients who did not receive PI-
88. The final data is expected to be released by the second quarter
of 2007. (December 16, 2006)
Doxorubicin Transdrug Anti-liver cancer BioAlliance Pharma Phase
II/III
Comments: Drug-loaded nanoparticles that are used for the delivery
of drugs though intra-arterial, intravenous, or oral administration
to treat or slow down progression of primary liver cancer.
Initiation of phase II studies have been approved in France. The
phase II study will enroll 50 patients over three months. A larger
Phase III trial is also being planed that will expand the trial to
include up to 200 patients treated for 12 months. The Phase II and
III study will evaluate the disease progression to assess the
disease progression of liver cancer. Doxorubicin Transdrug has been
granted orphan drug status by the EMEA (Europe) and FDA (United
States). (December 16, 2006)
Nexavar (sorafenib) Anti-liver cancer Onyx Pharmaceuticals Phase III
Comments: It has been reported that in two clinical trials that that
Nexavar significantly improved overall survival rates of patients
with liver cancer and without any adverse events. Based on these
data, the company has halted the clinical trial so that all the
patients (including the placebo arm) in the trial could receive
Nexavar. According to a company press release, Onyx plans to seek
approval from the FDA and European health authorities as soon as
possible.

Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.
announced on June 27, 2007 that a Supplemental New Drug Application
(sNDA) for Nexavar(R) (sorafenib) tablets has been submitted to the
U.S. Food and Drug Administration (FDA) for the treatment of
patients with hepatocellular carcinoma (HCC), the most common form
of liver cancer. The company announced on August 20, 2007 that the
FDA has granted Nexavar priority review, which means that the review
process is expediated and the FDA will take action within sex months
of the date on which the FDA received the application. (September
04, 2007)



Drugs on Hold

Drug Name Drug Category Pharmaceutical Company Clinical Phase
XTL-6865 (formerly HepX-C) Monclonal Antibody XTL Biopharmaceuticals
Phase I
Comments: Results from a phase I trial evaluating XTL-6865 found
that it was safe in the doses given. XTL Bio announced that it is
seeking a collaborative partner for future development of the drug.
A future clinical trial will evaluate this compound in patients with
hepatitis C undergoing liver transplantation. XTL is considering
selling the rights to XTL-6865 or pursuing clinicial trials with a
partner. (June 8, 2007)
HCV-796 Polymerase Inhibitor ViroPharma/Wyeth Phase II/III
Comments: Phase II studies began recruiting and are expected to
complete enrollment in the second quarter of 2007. The Phase II
study will evaluate the safety, tolerability, antiviral activity,
and pharmacokinetics of HCV-796 in combination with pegylated
interferon plus ribavirin vs. pegylated interferon plus ribavirin in
HCV genotype 1 treatment naïve patients and in genotype 1 patients
who were non-responders to a previous course of HCV treatment.
Treatment duration will be 48 weeks with a 24 week follow-up period.
4 week data will be released in the 3rd quarter of 2007; 12-week
data will be released in the 4th quarter of 2007. EASL: Phase 1b
data (in combination with PEG_Intron) reported that there was an
additive antiviral effect across multiple genotypes in treatment
naïve patients. The HCV-796 twice daily dose used in combination
with Peg-Intron was generally well-tolerated – side effects were
consistent with the known side effects of interferons. There were no
dose limiting toxicities reported. On June 13, 2007, Viro Pharma
reported that the enrolment in 500 mg arm of the trial has been
completed. On June 27, 2007 ViroPharma announced that the FDA
granted fast track designation to HCV-796. Clinical Trial On-Hold:
On August 10, 2007 ViroPharma announced that it is discontinuing the
dosing of HCV-796 due to safety concerns. Viropharma will continue
to monitor the study participants for safety issues and the
effectiveness of the drug in patients treated. ViroPharma in
collaboration with Wyeth will determine the next steps in the
development of HCV-796 based on the review of safety and efficacy
data (August 17, 2007)
NM283 (Valopicitabine) Polymerase Inhibitor Idenix Pharmaceuticals
Phase III
Comments:. Study 1--Non-responder study: Results reported from EASL
found that the trial failed to meet its goal, with no patients in
this difficult to treat group responding to the treatment. Study II –
Treatment naïve study: Phase II study results were released and it
was found that 72.2% of treatment naïve patients receiving the
valopicitabine, pegylated interferon plus ribavirin triple therapy
were HCV RNA negative after12 weeks compared to 61.5% in the group
receiving pegylated interferon plus ribavirin. Idenix announced that
they will be beginning a phase IIb dosing study of valopicitabine
(200 and 400 mg dose) in combination with pegylated interferon plus
ribavirin in about 300 genotype 1 treatment naïve patients towards
the end of 2007 and are planning a phase III study of triple therapy
for 2008. In July 2007 the FDA placed the current clinical developed
on hold after valopicitabine failed a risk/benefit analysis
performed by the FDA. Idenix's CEO stated that he is not optimistic
about the future development of valopicitabine (July 28, 2007)