There are many compounds being studied to treat
hepatitis C. A number of compounds for these targets are in early
“test-tube” development or pre-clinical “animal” development phases.
Most of these compounds, however, will never make it to trials in humans
(clinical studies). In fact, only one in 1,000 compounds makes it to
human testing. Of those drugs that make it to human testing only 1 in 5
will receive FDA marketing approval. Therefore, every effort has been
made to focus this list only on treatments that are known to be in
current active clinical development in human subjects.
There are many new drugs in development to treat
hepatitis C. When new drugs are tested they will be compared to the
current standard of care—the combination of pegylated interferon and
ribavirin. In addition, most experts believe that when new drugs are
approved to treat hepatitis C that they will be used in combination with
pegylated interferon and ribavirin.
When a company is ready to proceed to clinical
trials, it files an Investigational New Drug Application (IND) with the
Food and Drug Administration (FDA). Most clinical trials are designated
as phases I, II, or III, and sometimes IV based on the type of questions
that the study is seeking to answer.
The testing of new drugs is a long process that
typically takes about 12 years from pre-clinical testing to FDA approval
and marketing to the general public. To see a chart showing the timeline
for new drug development, click
here.
|
Drug Name |
Drug Category |
Pharmaceutical Company |
|
| GS3192/ACH806 |
Protease Inhibitor |
Gilead/Achillion |
Phase I |
| Comments: Enrollment in the phase 1
trial is expected to begin August 2006. |
| BLX-883 |
Locteron-interferon |
Biolex Therapeutics |
Phase I |
| Comments: A form of interferon
being tested with a new technology (LEX System ™) for
controlled-release of Locteron (injection every two weeks
instead of the weekly injection for Peg-Intron). A phase I study
of 27 healthy volunteers was reported at EASL and found Locteron
demonstrated that it was safe and well-tolerated. A phase II
study is being planned for the second half of 2006. |
| Alinia (nitrazoxanide)
|
Thiazolides |
Romark |
Phase I |
| Comments: A double-blinded,
placebo-controlled clinical trial of Alinia as oral monotherapy
for 20 HCV patients administered one tablet 500 mg twice daily
was reported. It was found that 50% of the patients had
undetectable HCV RNA at the end of 24 weeks of treatment
compared to none of the patients in the placebo group (P=0.03).
The drug was well tolerated with no significant side effects.
The company has filed an Investigational New Drug (IND)
Application with the U.S. FDA and plans to seek Fast-Tract
designation. |
Bavituximab
(formerly Tarvacin) |
Anti-Phospholipid Therapy |
Peregrine
|
Phase I |
| Comments: A phase I dose escalation
study to evaluate the safety, tolerability and biological
activity of bavituximab by infusion in 32 HCV positive patients
is underway. Patient enrollment is complete and clinical trial
results are expected in 2006. Early data reported that half of
the patients experienced greater than 75% reduction in viral
load after one dose. Second pahse of the study for repeated
dosing is underway. |
| Oral Interferon alpha
|
Oral Interferon |
Amarillo Biosciences |
Phase I |
| Comments: Testing low dose oral
administration of alpha interferon absorbed through mucosal
membranes. |
| NOV-205 |
Immunomodulator |
Novelos |
Phase I |
| Comments: A trial in the Russian
Federation found that NOV-205 greatly reduced HCV viral load and
was well-tolerated. A phase I clinical trial in the U.S. is
expected to begin in July 2006. |
| CGI 5005 |
Vaccine |
GlobeImmune |
Phase IB |
| Comments: A form of therapeutic
vaccine that is believed to stimulate the immune system to help
fight a variety diseases. An on-going Phase 1b double-blinded,
placebo controlled, dose-escalating, multi-center trial
evaluating the safety, immunogenicity, and efficacy of GI-5005
is underway. |
| HCV-796 |
Polymerase Inhibitor |
ViroPharma
/Wyeth |
Phase IB |
| Comments:
Results from a multiple dose study found that HCV-796
monotherapy given for 14 days displayed dose-related antiviral
activity in multiple genotypes. The 500 to 1000 mg dose given
twice a day achieved the best response with HCV RNA levels
reduced 96-97 percent and is considered safe and well-tolerated.
HCV-976 is also undergoing clinical trials in combination with
pegylated interferon. |
| Comments: Inhibits HCV genotype 1
polymerase |
| HCV/MF59 |
Vaccine |
Chiron |
Phase I |
| Comments: Two vaccines are being
tested in collaboration with CSL Ltd. and St. Louis University.
Early clinical data from St. Louis University reported that 60
patients who received 4 different doses of vaccine produced HCV
antibodies in all of the patients. The study is on-going. |
| ANA971 |
Isatoribine |
ANADYS |
Phase I |
| Comments: A prodrug of isatoribine.
A recent clinical study of 48 subjects, including 28 patients
infected with hepatitis C reported that the intravenous
administration of ANA971 was well tolerated and safe at all
doses tested. It has shown biological activity against hepatitis
C as well significant reductions in HCV RNA (viral load). |
| EMZ702 |
Interferon Enhancer |
Transition
Therapeutics |
Phase I/II |
| Comments: A medication that is
believed to enhance interferon properties. A trial of 25
hepatitis C nonresponders has begun in Canada. The study
participants – people who did not respond to pegylated
interferon plus ribavirin therapy – are being treated with
EMZ702 twice a week along with pegylated interferon plus
ribavirin. Preliminary data show that 7 of 11 patients in the
trial achieved more than a 90% reduction in HCV RNA, with 3 of
11 achieving a greater than 99% reduction in HCV RNA. There were
no serious adverse events reported. |
| AVI-4065 |
Antisense Compound |
Biopharma
|
Phase I/II |
| Comments: Phase I studies have been
completed by enrolling and evaluating about 30 healthy
volunteers at 3 doses (subcutaneous injections) daily for 14
days. No adverse events were noted at any dosing range. A second
study is planned with 40 HCV positive (including previous
treatment non-responders) patients to assess efficacy over a
minimum of treatment for 14 days. A report on the second phase
of AVI-4065 was released in May 2006 and found that it exhibited
a favorable safety and tolerability profile in all the patients
treated so far. In the few patients treated there was a slight
decrease in viral load. Active enrollment and evaluation is
ongoing. More clinical trial results are expected around the end
of 2006 Treatment duration has been extended to 28 days for one
study arm and 56 days for the other study arm. |
| ANA975 |
Isatoribine |
ANADYS |
Phase I |
| Comments: A prodrug of isatoribine.
In a dose (400-1200 mg administered intravenously) and safety
study, ANA975 was generally well-tolerated with no serious side
effects. ANA975 achieves plasma isatoribine exposures comparable
to those previously shown to reduce plasma HCV RNA in
chronically infected patients. A phase Ib study with healthy
subjects will be initiated in January 2006. Co-licensing
agreement with Novartis. Trial suspended until assessment of
13-week pre-clinical toxicology studies (3/26/2006). |
| R1626 |
Polymerase Inhibitor |
Roche |
Phase I |
| Comments: Eighteen treatment-naïve
patients with HCV genotype 1 received either 1500 mg or 500 mg
twice daily for 14 days. After 14 days of follow-up, those who
received the 1500 mg dose experienced a median 1.2 log IU/mL
(range 0.5 to 2.5) reduction in HCV RNA. R1626 was
well-tolerated, with no serious adverse events or early
withdrawals. |
| XTL-2125 |
Polymerase Inhibitor |
XTL |
Pase I |
|
Comments: In May 2006 XLT Biopharmaceuticals announced it will
initiate a Phase I dose-escalating clinical trial to evaluate
the safety, tolerability and antiviral activity of single and
multiple doses of XTL-2125. The trial will enroll 48 patients. |
| CPG 10101 (Actilon)
|
Immunomodulator |
Coley |
Phase I/II |
| Comments: The results from two
clinical trials look promising. In one study of 60 previous
non-responders (mostly genotype 1), patients receiving CPG 10101
monotherapy achieved reduced HCV viral load. In the second
study, 74 HCV genotype 1 patients (who relapsed after prior
therapy) were given CPG 10101 (in various doses) alone or in
combination with pegylated interferon plus ribavirin. 86% of
the patients who received the triple combination achieved early
virological response at week 12, compared to 60% of those
receiving standard therapy. In both trials CPG 10101 was
generally well-tolerated. In May 2006 CPG 10101 was granted
Fast Track designation by the FDA. |
| XTL-6865 (formerly HepX-C) |
Monclonal Antibody |
XTL |
Phase I/II |
|
Comments: In a study presented at AASLD 2005, patients
were given XTL-6865 during and after liver transplantation which
resulted in a HCV RNA reduction. At day one following liver
transplantation the median reduction was 1-log (90%) of HCV RNA
in the highest dose group (240 mg). A single antibody version
of this product was tested in a pilot clinical program that
included both Phase I and Phase II clinical trials. In April
2005, XTL submitted a U.S. investigational new drug application
(IND) to the FDA in order to commence a Phase Ia/Ib clinical
trial in late 2006 for XTL-6865, the dual-MAb product. |
| G126270 |
Anti-fibrotic |
GlaxoSmithKline |
Phase II |
| A phase II study is underway to
examine the safety and effectiveness of G126570 compared to
placebo to improve histology (liver scarring) in previous
treatment non-responders/relapsers. |
| SCH 503034 |
Serine Protease Iinhibitor |
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. |
| IC41 |
Therapeutic Vaccine |
Intercell |
Phase II |
| Comments: a combination synthetic
therapeutic vaccine (medicines to increase the T-cell response
plus peptides identified through studies of people with natural
immunity to HCV or successful response to HCV therapy). IC41 has
completed phase I & phase II studies and has been shown to have
a good safety profile in healthy adults and previously treated
HCV patients who failed to achieve a successful treatment
outcome. In the HCV patients there was an increase in T-cell
response and a temporary reduction of HCV RNA (viral load).
Larger phase III trials are being planned for 2006 and 2008.
|
| Medusa Interferon
|
Interferon — Long Acting |
Flamel
Technologies |
Phase II |
| Comments: Preliminary results from
Phase I and II demonstrated that IFN-alpha-XL (a long acting
form of interferon) was safe and well tolerated showed a
positive effect on the HCV viral load. Data from the two phase
II clinical trials is expected in 2006. |
| VX-950 |
Protease Inhibitor |
Vertex |
Phase II |
| Comments: Results from a Phase II
clinical trial in 12 patients who took VX-950 (750 mg) oral
tablet every 8 hours for 28 days in combination with Pegasys and
ribavirin found that there was a 99.9% reduction in HCV RNA.
VX-950 in combination with Pegasys and ribavirin was
well-tolerated and no serious adverse events were reported. In
May 2006 Vertex announced the initiation of two large
studies—PROVE 1 (U.S.) and PROVE II (Europe). Recruitment for
this trial is expected to begin in June 2006. In December 2005
the FDA granted Fast Track designation for VX-950.
Special Report. In July 2006, it was announced that
Johnson and Johnson and Vertex had entered into an agreement for
sales of VX-950 in various markets around the world with upfront
payments and future percentages when VX-950 is marketed. |
| Albuferon |
Interferon — Long Acting |
Human Genome Sciences |
Phase II |
| Comments:A form of time-released
interferon that is produced by fusing human serum albumin to
interferon. In a phase IIb study, it was found that a once
monthly dosing of Albuferon plus ribavirin produced lower
treatment response rates than the comparator arm of Pegasys plus
ribavirin, but there was a slightly higher response rate in the
group that received Albuferon twice weekly plus ribavirin
compared to Pegasys plus ribavirin. In a second trial, Albuferon
at higher doses plus ribavirin achieved good early treatment
results. SVR data from this trial is expected towards the end of
2006. In June 2006 it was announced that Human Genome Sciences
and Novartis entered into an agreement where Novartis will pay
Human Genome Sciences up to $507 million to help develop and
sell Albuferon. |
| IDN-6556 |
Caspase Inhibitor |
Pfizer |
Phase II |
| Comments:
Caspase inhibitors do not have any direct antiviral properties,
but are believed to preserve the cell structure and protect the
liver from damage caused by HCV. Phase I study completed in May
2002 which included patients with stable hepatitis C infection.
Data from a Phase 2a clinical trial of an oral formulation of
IDN-6556 in patients infected with HCV reported positive safety
and tolerability of the drug as well as its ability to reduce
elevated aminotransferase (ALT and AST) levels. The FDA granted
Orphan Drug Designation to IDN-6556 for use with organ
transplantation in May 2006. |
| E-1 |
Therapeutic Vaccine |
Innogenetics |
Phase II |
| Comments: Currently in trials to
study the effectiveness of this therapeutic vaccine in slowing
down fibrosis progression. On June 1, 2005, it was reported that
the study results from the trial were inconclusive (the results
between the vaccine treated group and the placebo group did not
reach a statistical significance) so the study was extended to
an additional 15 months. |
| Civacir |
Polyclonal Antibody |
NABI |
Phase II |
| Comments: Prevention of
post-transplant recurrence of HCV. Preliminary results show
positive safety and pharmacokinetics results. On Feb 1, 2006 the
FDA granted fast track designation. |
| Omega Interferon
|
Interferon |
Intarcia |
Phase II |
| Comments: Uses
an implantable infusion pump that releases a steady amount of
Omega for about 1 month. An ongoing Phase II trial is evaluating
omega interferon alone and in combination with ribavirin in 102
HCV treatment naïve patients with genotype 1. Preliminary
results show an early virological response of 84% in the
ribavirin combination arm and 60% in patients treated with Omega
alone. SVR data will be available by the end of 2006. |
| Multiferon |
Interferon — Long Acting |
Viragen |
Phase II |
| Comments: A type of natural
interferon that has been approved to treat HCV in various
countries outside of the United States. |
| Suvus (Methylene Blue)
formerly BIVN-401 (Virostat) |
Antiviral |
Bioenvision
|
Phase II |
| Comments: Clinical trial included
25 patients (genotype 4) who were previous non-responders to HCV
therapy; 64% of patients had cirrhosis. At 50 days 88% of
patients had a reduction in viral load greater than 70%. No
adverse events were reported. Larger studies are being designed. |
| MX-3253 (Celgosivir)
|
Glucosidase I inhibitor |
Migenix |
Phase II |
| Comments: A
mono-therapy trial found that celgosivir (oral formulation) was
safe and had a modest affect on HCV, but in preclinical studies
it was found that celgosivir also had a synergy with interferon.
Currently, an on-going study is evaluating celgosivir in
combination with pegylated interferon for up to 12 weeks in HCV
patients who were non-responders or partial responders to
previous treatment with pegylated interferon-based therapy –
Enrollment of 57 HCV patients was completed in July 2006. Study
results are expected in October 2006. A new Phase IIb study in
HCV positive genotype 1 patients who are treatment naïve (never
been treated) will begin in June 2006. 30 patients will be
recruited and randomized to receive celgosivir plus
peginterferon alfa-2b plus ribavirin, celgosivir plus
peginterferon alpha or peginterferon alfa-2b plus ribavirin for
12 weeks. Results from this trial are expected late 2006 or
early 2007. |
| VGX-410C |
IRES Inhibitor |
VGX Pharmaceuticals |
Phase II |
| Comments: Two trials are currently
underway. The first trial (University of Pennsylvania) will
recruit 28 patients to be treated with VGX-410C for 28 days; It
was recently announced that another study site at St. Louis
University was being added |
| NM283 (Valopicitabine) |
Polymerase Inhibitor |
Idenix |
Phase III |
| Comments: NM283 is currently in two
different phase III studies. In the trial of non-responders,
NM283 (in three arms) plus pegylated interferon or pegylated
interferon plus ribavirin reported an average 2.5 to 3.0 log
decrease in HCV RNA (viral load). NM 283 was generally
well-tolerated except three patients experienced severe
gastrointestinal events requiring the trial to amend the
protocol to a lower dose of 200 or 400 mg for both clinical
trials. The other trial of NM283 combined with Pegasys has
concluded enrollment of 174 treatment naïve patients.
Preliminary results from 10 patients who have reached 24 weeks
of treatment found a greater than 99.99% reduction in HCV RNA
(viral load) and that 8 of the 10 patients were HCV RNA
negative. |
| Interferon beta-1a (REBIF)
|
Interferon |
Ares-Serono |
Phase III |
| Comments: A phase 3 study of
r-IFN-beta in 250 patients in Asia with chronic hepatitis C
found a proportion of patients who achieved sustained
virological response (SVR), defined as an absence of detectable
HCV RNA in serum after 24 weeks of treatment and 24 weeks of
observation. 26.6% in the r-IFN-beta group achieved SVR versus
no responders in the placebo group. |
| Viramidine |
Nucleoside Analogue |
Valeant |
Phase III |
| Comments: A prodrug of ribavirin
that specially targets liver cells. In a recently released study
(VISER I) comparing Peg-Intron with either viramidine (fixed
dose) or ribavirin (weight based) found that the incidence of
anemia was statistically lower in the viramidine group, but that
the SVR rates in the viramidine was not shown to be
‘non-inferior’ to ribavirin (38% vs. 52%, respectively). The
other large international trial with viramidine (VISER II) and
ribavirin (using Pegasys) is expected in 2006-2007. It is now
believed that dosing for viramidine should have been weight
based in the clinical trials rather than the fixed based dose
used. |
| Thymosin alfa-1 (Zadaxin)
|
Immunomodulator |
SciClone |
Phase III |
| Comments: In a company press
release, final results from the second phase III study indicate
that Zadaxin plus pegylated interferon did not demonstrate a
statistically significant improvement compared with pegylated
interferon alone. It was noted that the company will now focus
their efforts on advanced-stage malignant melanoma. |
| Consensus interferon
(Infergen) |
Interferon |
Valeant |
Phase IV |
| Comments: Infergen is being studied
in ongoing clinical trials to establish additional labeling for
daily use with ribavirin. Enrollment in the Phase 3 trial
(DIRECT) was completed in mid-2005 and the trial is expected to
be completed in 2007. The DIRECT trial, which should be
completed in 2007, is evaluating the safety and efficacy of both
9mcg and 15mcg doses of daily Infergen in combination with
ribavirin in non-responders. |
| Amantadine |
Broad Antiviral |
Endo Labs Solvay |
Phase IV |
| Comments: Anti-flu
agent on the market. Has shown mixed results of efficacy in
combination with interferons. |
