Hepatitis C Treatments in Current Clinical Development

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Hepatitis C Treatments in Current Clinical Development

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Hepatitis C Treatments in Current Clinical Development

Alan FranciscusEditor-in-Chief

PDF (download) There are many potential targets being pursued by drugs treating HCV. 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.

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.

Study Phases

In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety. In Phase III studies, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. In Phase IV studies, the drug is already on the market for a particular indication, but is now being tested for a different indication, use, or disease.

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.

The following table will be updated as clinical developments move forward:Quick Reference Chart Click on the name of the drug to view the history of the drug development.

Phase I

Phase II

Phase III

Phase IV

ANA971

ANA245

REBIF

Infergen/Consensus

Oral Interferon alpha

HepX™-C

IP-501

Amantadine

JTK 003

Rituximab (Rituxam)

Viramidine

EMZ702

NM283

Zadaxin

HCV/MF59

ISIS 14803

SCH-6

E-1

HCV-796

Civacir

Tarvacin

Merimebodib- VX-497

SCH 503034

Interferon gamma-1b

AVI-4065

Omega Interferon

Multiferon

BILN 2061

IDN-6556

Ceplene

Albuferon

Medusa Interferon

IC41

VX 950

CPG 10101

BIVN-401 (Virostat)

MX-3253 (Celgosivir)

Table of Hepatitis C Drugs in Current Clinical Development Click on the name of the drug to view the history of the drug development.

Drug Name

Drug Category

Pharmaceutical Company

Tarvacin

Anti-Phospholipid Therapy

Peregrine

Phase I

Comments: It was announced that the FDA has approved a phase I dose escalation study designed to evaluate a single intravenous infusion of Tarvacin in up to 32 patients with chronic Hepatitis C virus (HCV) infection.

Oral Interferon alpha

Oral Interferon

Amarillo Biosciences

Phase I

Comments: Testing low dose oral administration of alpha interferon absorbed through mucosal membranes.

HCV-796

Polymerase Inhibitor

ViroPharma/Wyeth

Phase IB

Comments: To date, HCV-796 has demonstrated potent efficacy in inhibiting viral replication in cell-based assay systems and in an animal model for hepatitis C. In these studies, HCV-796 antiviral activity was highly selective and significantly reduced HCV RNA levels in an in vitro replicon assay.

JTK 003

Polymerase Inhibitor

AKROS Pharma

Phase I

Comments: Inhibits HCV genotype 1 polymerase

HCV/MF59

Vaccine

Chiron

Phase I

Comments: In collaboration with CSL Ltd. and St. Louis University.

SCH-6

Serine Protease

Schering

Phase I

Comments: In tests it was found the SCH-6 could protect the cell's defenses and actually may prevent the HCV virus from blocking the immune response and help restore the body’s natural antiviral response.

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).

AVI-4065

Isatoribine

Biopharma

Phase I

Comments: On September 28, 2005 it was announced the initiation of a clinical trial on the safety and effectiveness of AVI-4065 on healthy patients with chronic hepatitis C.

SCH 503034

Protease inhibitor

Schering

Phase I

Comments: Phase 1 clinical data will be presented at AASLD in November 2006. SCH 504034 is being tested as both a monotherapy and in combination with PEG-Intron in genotype 1 patients who were nonresponders to peginterferon plus ribavirin.

ANA245

Isatoribine

ANADYS

Phase I/II

Comments: Interim results of the Phase 1B clinical trial show that isatoribine is biologically active in adults with chronic HCV infection and results from dosing a cohort of six HCV infected patients with 800mg of isatoribine showed a statistically significant reduction of viral load (p=0.03) at the end of one week, with a median change in viral load from baseline of -0.94 log10 units.

CPG 10101 (Actilon)

Immunomodulator

Coley

Phase I/II

Comments: In a study of 45 HCV positive patients receiving 20 mg dose twice weekly a 90% reduction in HCV viral load was achieved. The drug was found to be safe and well tolerated. Studies on Actilon monotherapy as well as in combination with pegylated interferon plus ribavirin have been initiated .

Rituximab (Rituxam)

Anti-CD20 Monoclonal Antibody

Genetech/IDEC

Phase I/II

Comments: Under investigation for treatment of cryoglobulinemia. Currently approved for non-Hodgkin's lymphoma.

NM283 (Valopicitabine)

Polymerase Inhibitor

Idenix Pharmaceuticals

Phase I/II

Comments: HCV polymerase inhibitor was found to be effective in reducing HCV RNA viral loads in 99.0% of 9 patients in an on-going phase II clinical trial and no serious side effects were observed. As of June 1, 2005, enrolment in a study of 170 HCV patients who are treatment resistant to current medications has been completed. This is a six month study comparing NM283 plus Pegasys with ribavirin plus Pegasys. Indenix is planning a larger phase III study in 2006.

HepX™-C

Monclonal Antibody

XTL

Phase I/II

Comments: Phase I studies on 35 chronic HCV patients indicated good safety and bioactivity. Phase II study of HCV prophylaxis on post liver transplant patients underway.

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 trials are being planned for 2006 and 2008.

Medusa Interferon

Longer acting interferon

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 mid December 2005.

VX-950

Protease Inhibitor

Vertex

Phase II

Comments: In a study of 34 HCV positive patients it was found that VX-950 produced substantial reductions (1,000 fold) in HCV RNA (viral load) in all doses. The 750 mg dose produced a 25,000 fold decrease in viral load in 4 out of 8 patients. VX-950 was found to be safe and well tolerated. Additional studies are being planned using VX-950 monotherapy, as well as in combination with pegylated interferon.

Albuferon

Longer Acting Interferon

Human Genome Sciences

Phase II

Comments: A form of time-released interferon that is produced by fusing human serum albumin to interferon. In phase II clinical trials Albuferon was found to be safe and well tolerated and produced a 99.9% decrease in HCV RNA (viral load). It was announced on June 1 that the clinical trial of albuferon plus ribavirin has begun in treatment naive HCV patients. The active control group will receive Pegasys plus ribavirin. A minimum of 440 patients will be enrolled in the study.

IDN-6556

Caspase Inhibitor

Idun Pharmaceuticals

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.

ISIS 14803

Antisense

Isis Pharmaceutical / Elan

Phase II

Comments: Genetically inhibits translation (production) of disease-causing proteins. This compound appears to be well-tolerated, with minimal adverse effects. A larger trial combining ISIS 14803 with pegylated/ribavirin is currently underway.

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.

VX-497 (Merimebodib)

IMPDH inhibitor

Vertex

Phase II

Comments: The preliminary results of a phase II study showed the combination of VX-497, pegylated interferon and ribavirin was safe and well-tolerated, and VX-497 exhibited an antiviral effect against HCV.

Omega Interferon

Interferon

BioMedicine

Phase II

Comments: New formulation intended to target the liver specifically in order to reduce the side effects in other tissues.

Multiferon

Long Acting Interferon

Viragen

Phase II

Comments: Company is making long-acting pegylated version of product in cooperation with Valantis.

Ceplene

Histamine

Maxim

Phase II

Comments: Completed phase II studies. Currently in clinical trials with pegylated interferon.

BILN 2061

Serine Protease

Boehringer - Ingelheim

Phase II

Comments: Intended to block viral replication. Shows dramatic decrease in HCV viral load with only 48 hours of therapy. One of the most promising potential new HCV therapies. However, phase II trials were put on hold until potential toxicities seen in monkeys taking high doses are resolved.

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 recent mono-therapy trial showed that mx-3253 was safe and had a modest effect on HCV. A combination trial using pegylated interferon is being planned.

Interferon beta-1a (REBIF)

Interferon

Ares-Serono

Phase III

IP-501

Anti-fibrotic

Indevus

Phase III

Comments: Anti-fibrotic agent to treat/prevent cirrhosis. Seems to stimulate collagenase to breakdown collagen – a component of scar tissue.

Viramidine

Nucleoside Analogue

Valeant Pharmaceuticals Int’l

Phase III

Comments: A prodrug of ribavirin that specially targets liver cells. In phase II studies of viramidine and pegylated interferon treatment response rates were similar between the ribavirin and viramidine arms, but the incidence of hemolytic anemia observed in the viramidine arm was 4% compared to 27% in the ribavirin arm. Larger studies are underway.

Thymosin alfa-1 (Zadaxin)

Immunomodulator

SciClone

Phase III

Comments: Boosts the immune system. Used in combination with interferons and ribavirin. Phase III clinical trials in the U.S. are fully enrolled with over 1,000 patients receiving Zadaxin in combination with pegylated interferon. SVR data is expected in early 2006.

Consensus interferon (Infergen)

Interferon

InterMune

Phase IV

Comments: Data from on-going phase IV clinical trials of high daily dosing of Infergen in combination with ribavirin looks promising

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.

Recently cancelled clinical trials:

Drug Name

Drug Category

PharmaceuticalCompany

Clinical Phase

Heptazyme

RNA inhibitor

RPI

Studies Cancelled

Levovirin

Nucleoside Analogue

Valeant Pharma-ceuticals Int’l

Studies Cancelled

Interleukin-10

Anti-fibrotic

Schering-Plough

Studies Cancelled

R803

Non-nucleoside HCV Polymerase Inhibitor

Rigel Pharmaceuticals

Studies Cancelled

HCV-086

ViroPharma/Wyeth

Studies Cancelled(The listing of the pharmaceutical industries are for information only and do not constitute endorsement of the pharmaceutical companies or the drugs in development)

http://www.hcvadvocate.org/hepatitis/hepC/HCVDrugs.html

Kathy Brunow