Hepatitis C Treatments - Hepatitis C Drugs in Development

	Back to Hepatitis C Updated: August 5, 2008 Hepatitis C Treatments in Current Clinical Development Alan Franciscus Editor-in-Chief PDF (download)   About Clinical Trials Quick Reference Chart Polymerase / Protease Inhibitors in Development Drugs in Clinical Development ( General) Interferons in Development Vaccines in Development Anti Cancer Drugs in Development Adjunct Therapies Clinical Trials on Hold Clinical Trials that Have Been Cancelled   Quick Reference Chart The following tables will be updated as clinical developments move forward: Phase I Phase II Phase III Phase IV On Hold HCV/MF59 Oral Interferon alpha Viramidine Infergen/ Consensus JBK-122 Bavituximab (Tarvacin) Civacir Albuferon     IL-29 (PEG-Interferon lambda) Omega Interferon ZADAXIN® (thymalfasin or thymosin alpha 1)     NOV-205 PF-03491390 (formerly IDN-6556) Nexavar     ITMN-191 IC41 VX 950 (telaprevir)     R1656 MX-3253 (Celgosivir) SCH 503034 (boceprevir)     Belerofon (oral) VGX-410C ThermoDox (doxorubicin)     R7128 R1626       A-831 DEBIO-025       PeviPROTM GV1001       PYN17 PI-88       TG4040 BLX-883 (Locteron)       ChronVac-R MitoQ       GSK625433 SOV-07       IMO-2125 Alinia (nitazoxanide)       LGD-4665 Z10-101       CF102 VCH-759       VCH-916 Oglufanide disodium       VX-500 TMC435350       PF-00868554 GGI-5005 (Tarmogen)       SPC3649 (LNA-antimiRTM-122) CTS-1027       ABT-333 Eltrombopag       GS 9190         ANA598         IDX184         Drugs in Current Clinical Development   Polymerase/Protease Inhibitors in Development Drug Name Drug Category Pharmaceutical Company Clinical Phase IDX184 Polymerase Inhibitor Idenix Phase I Comments: On July 29, 2008 Idenix announced the initiation of a phase I study of IDX184 a once-daily oral HCV polymerase inhibitor (August 5, 2008). ANA598 Polymerase Inhibitor Anadys Pharmaceuticals Phase I Comments: On June 2, 2008 Anadys announced that the dosing of ANA598 in healthy volunteers has begun. The Phase I trial is being initiated to study the safety, tolerability and pharmacokinetics of ANA598 in healthy volunteers. (August 5, 2008) ABT-333 Polymerase Inhibitor Abbott Phase I Comments:On June 11, 2008, Abbott announced the initiation of a Phase I study to test the safety, tolerability, antiviral activity and pharmacokinetics of ABT-333 in healthy volunteers and in HCV positive individuals.  (June 11, 2008) VCH-916 HCV Polymerase Inhibitor Virochem Phase I Comments: In a small study of healthy volunteers, VCH-916 was found to be generally safe and well-tolerated and achieved plasma concentrations proportional to the dose given. Based on these results a 14-day study of HCV genotype 1 treatment-naïve subjects is being planned. (May 21, 2008) MK7009 HCV Protease  Inhibitor Merck Phase I Comments:  A phase I double blinded, placebo controlled trial testing the safety and efficacy has been initiated.  (May 28, 2008) PF-00868554 HCV Polymerase Inhibitor Pfizer Phase I Comments:  A phase I trial is underway evaluating safety, tolerability and antiviral activity in HCV genotype 1 patients.  (May 28, 2008) VX-500 HCV Protease Inhibitor Vertex Phase I Comments:  VX-500 recently began a phase I dose escalation and safety study in healthy volunteers.  Vertex expects to begin a trial in HCV patients in mid-2008.  (May 28, 2008) GS 9190 Polymerase Inhibitor Gilead Phase I Comments:  AASLD 2007:  Results from two parts of a phase I study were released.  Part 1: 31 patients treated with single escalating doses of GS 9190, and Part 2: 23 patients received various doses twice daily.  Both studies found that GS 9190 was generally well-tolerated and showed antiviral activity against HCV. In these studies there were some concerns over a potential cardiac problem (irregular heart rhythms) so Gilead has initiated another study to determine whether the cardiac problem was caused by GS 9190.  If this problem can be resolved, Gilead will advance GS 9190 into larger studies.  (November 18, 2007) 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) ITMN-191 (R-7227) Protease Inhibitor InterMune Phase I Comments: On May 29, 2008 InterMune announced it has begun dosing of a 14-day phase 1b trial evaluating ITMN-191 in combination with Pegasys and ribavirin (triple therapy) in treatment-naïve genotype 1 patients.  The company also reported that the results from a trial using ITMN-191 in HCV treatment-experienced patients warranted continued development of ITMN-191. (May 29, 2008) R7128 Polymerase Inhibitor Pharmasset/Roche Phase I Comments: On January 7, 2007, Pharmasset announced the results of a trial in 50 HCV treatment naïve patients which found that R7128 (dosed twice daily) when used in combination with Pegasys and ribavirin was safe, well-tolerated and there were no serious adverse events reported in the 4-week treatment period. In the group that received 1500 mg, 85% of the patients achieved undetectable HCV RNA. It was announced on April 24, 2008 that Pharmasset will add two 4-week arms to evaluate a 1500 mg BID (twice a day) dose in genotype 2 & 3 prior non-responders and 1000 mg BID in HCV genotype 1 treatment-naïve patients.  Results from these 4-week trials will be used to design further clinical trials.   On August 5, 2008, Pharmasset announced the preliminary results from a 31 patient study that found that the 1000 mg BID dose provided potent antiviral activity and the greatest margin of safety. Based on these results Pharmassett will advance the 1000 mg dose into larger trials. (August 5, 2008). VCH-759 Polymerase Inhibitor Virochem Phase II Comments: AASLD 2007: In a 10 day phase I study in which 32 treatment naïve HCV patients received different doses of VCH-759 (400 mg TID, 800 mg BID, and 800 mg TID) all patients achieved a 1 log10 decrease in HCV RNA but the higher dose arm of 800 mg TID achieved 2.5 log10 decrease.  The drug was generally well-tolerated.  A Phase 2, Multicenter, Randomized, Double-Blinded, and Placebo-Controlled Study of the Antiviral Activity, Safety and Pharmacokinetics of VCH-759 is underway. (November 19, 2007) R1626 Polymerase Inhibitor Roche Phase II Comments: EASL 2008:  Analysis of the end of treatment (EOT) response rates for 104 patients treated with R1626 plus Pegasys and ribavirin (4 weeks of triple therapy, then another 44 weeks of Peg/ribavirin) found that in the group given the 1,500 mg daily (plus Pegasys/ribavirin) there was an 84% (26 of 31 pts) EOT compared to 40% (13 of 20 pts) in the control arm that received Pegasys plus ribavirin, but no R1626.  In general the side effects were considered mild to moderate.  However, there is concern because of the incidence of grade 4 neutropenia (low white blood cells) which was the major reason for dose reductions and treatment discontinuations.  Roche has announced that their phase 2b study of R1626 is fully enrolled.  This study is testing different doses of R1626 (500, 100, and 1500 mg bid) and Pegasys (90 ug and 180 ug) plus standard ribavirin to find the best dose of R1626 that has the least amount of side effects.  May 21, 2008) TMC435350 Protease Inhibitor Medivir/Tibotec Phase II Comments: Following the successful completion of a phase I study with TMC435350 in both healthy volunteers and patients chronically infected with hepatitis C virus (HCV), Medivir announced a phase IIa study, TMC435350-C201, of the investigational hepatitis C (HCV) protease inhibitor TMC435350. The study will start shortly in Europe by Tibotec Pharmaceuticals Ltd., which is collaborating with Medivir on the development of TMC435350. TMC435350-C201 is a phase IIa proof-of-concept, blinded, randomized, placebo-controlled trial to assess the effectiveness, safety, tolerability, and pharmacokinetics of four different dose regimens of TMC435350 (25 mg daily, 75mg daily, 200mg daily, 400mg daily). 96 treatment-naïve and 24 treatment-experienced patients with chronic genotype-1 HCV infection will be enrolled in the trial which will be conducted at more than 20 sites in Europe. Patients will receive either TMC435350 or placebo once daily (qd) for 28-days. Standard of Care (SoC) treatment, peginterferon alpha-2a (Pegasys®) and ribavirin (Copegus®), will be provided for 48 weeks or, optionally, for 24 weeks for those patients with an undetectable at Week 20. Patients will be followed-up for 24 weeks after the end of standard of care (Peg/ribavirin) to allow evaluation of sustained virologic response (SVR). EASL 2008:  Data from 6 HCV patients who were prior treatment non-responders or relapsers showed that the 200 mg dose of TMC435350 (once a day) was associated with a median decrease of 3.9 log10 HCV RNA on day 6 of treatment. In the same study, 52 healthy volunteers were given TMC435350 and it was found to be safe and well-tolerated.  (May 21, 2008) SCH 503034 (Boceprevir) Serine Protease Inhibitor Schering Phase III Comments: EASL 2008:  Interim results from two studies were released at EASL. The HCV Sprint-1 (595 treatment naïve patients HCV genotype 1) preliminary data was released on August 4, 2008. The group treated with a lead-in phase of Peg-Intron plus ribavirin (standard doses) for 4 weeks followed with triple therapy (boceprevir/Peg-Intron/ribavirin) for another 44 weeks achieved 74% SVR12 (continued undetectable viral load 12 weeks after treatment ends). Patients who received 48-weeks of triple therapy (boceprevir, PegIntron and ribavirin), but who did not have a lead-in phase achieved a 66% SVR 12 EASL 2008: The results of treating 357 HCV genotype 1 prior null responders to pegylated interferon and ribavirin showed that the SVR rates were up to 14% in the groups that received the triple combination compared to 2% in the groups that received only PegIntron plus ribavirin. It is important to know that most patients in this study did not receive the highest dose of boceprevir. On May 21, 2008, Schering announced that they would begin 2 phase III studies to evaluate boceprevir in combination with PegIntron plus ribavirin in treatment-naïve and treatment-experienced patients. August 5, 2008) VX 950 (telaprevir) Protease Inhibitor Vertex Phase III Comments:  On January 23, 2008, Vertex announced that they will begin recruitment into a phase III clinical trial in March 2008.  The ADVANCE trial will be conducted in about 100 centers in the U.S., Europe and certain other countries.  The study will enroll approximately 1050 HCV genotype 1 treatment-naïve patients.  There will be 3 treatment arms comparing telaprevir in combination with pegylated interferon plus ribavirin for a treatment duration of 24 weeks.  The control arm will be patients treated with pegylated interferon plus ribavirin for 48 weeks (current standard of care).  This is the pivotal Phase III study that will be used to apply for FDA marketing approval, which Vertex expects to seek in late 2010.  In addition there will be various other studies that will be conducted in the United States and Europe including one that will look at less frequent dosing of telaprevir.  On May 13, 2008, Vertex announced that it has enrolled the first patient in the trial. EASL 2008:  Results from the phase II studies telaprevir (pill) taken every 8 hours, pegylated interferon (Pegasys) injected once a week, and weight-based ribavirin (pill, 1000/1200 mg/day) in genotype 1 patients were released. PROVE 1: 61% achieved a sustained virological response (SVR-24 week post treatment) in the group that received 24 weeks of treatment and 67% SVR in the 48 week treatment group. PROVE 2: 62% SVR12 achieved with 24 weeks of treatment compared to 68% SVR in the group that received 36 weeks of treatment. Side effects that required treatment discontinuation were higher in the telaprevir triple arms compared to the pegylated interferon plus ribavirin control arms. EASL 2008:   Preliminary results were released from a phase 2 study (Study 107) of genotype 1 patients who were enrolled in a previous phase II study and who were in the control arm – they had received Pegasys plus ribavirin (without telaprevir) and were either null responders, non-responders or relapsers in the PROVE 1, 2, 3 studies. The authors found that 84% of patients treated so far (60 pts) were HCV RNA undetectable (< 25 IU/mL) by week 4 and that the majority of patients who remained on therapy past week 4 continued to remain HCV RNA undetectable.  Results from a large trial treating treatment-experienced patient with telaprevir, Pegasys and ribavirin will be released mid-2008. PROVE 3:  On June 9th, Vertex released preliminary data of the Phase II study that treated prior nonresponders, relapsers and treatment breakthoughs with a combination of telaprevir, pegylated interferon, and ribavirin for 12 weeks followed by an additional 12 weeks of Pegasys plus ribavirin (total treatment duration 24 weeks).  It was reported that the SVR12 was 41% for non-responders, 73% for relapsers and 44% for breakthroughs.  Based on this data Vertex is initiating a Phase III study that is expected to begin enrollment in the third quarter of 2008.  For more information about Vertex’s clinical trials click here to read Vertex’s press release. (June 11, 2008)      Drugs in Clinical Development (General) Drug Name Drug Category Pharmaceutical Company Stage of Development SPC3649 (LNA-antimiRTM-122) microRNA Santaris Pharma Phase I Comments: On May 29, 2008 Santaris announced that it was commencing a study of SPC3649 in up to 48 healthy male volunteers who will receive SPC3659 or placebo.  The trial is a placebo-controlled, double-blind, randomized, single dose, dose-escalating safety study.  After establishing the safety and tolerability of the drug the next step would be to study the drug in HCV patients.  MicroRNA drugs are a new class of drugs and this trial is the first to test a microRNA in humans. (May 29, 2008) CF102 A3AR AGONISTS CAN-FITE Phase I Comments: Can-Fite announced the completion of a phase I clinical trial in 25 healthy adults.  In addition to determining the dosing range for future studies, CF102 was found to be safe and well-tolerated. (May 13, 2008) IMO-2125 TLR9 agonist Idera Pharmaceuticals Phase I Comments: On September 17, 2007 Idera Pharmaceuticals announced that it started enrollment of patients to study the safety, tolerability and antiviral properties of IMO-2125 in prior null-responder HCV patients. (September 18, 2007) PYN17 Botanical Phynova Phase I Comments: On September 12, 2007, Phynova announced completion of patient enrollment of 29 patients who will receive PYN17 or placebo. Results from the study found that it was well-tolerated with minor adverse events. Larger studies are being planned for 2008 (December 13, 2007). Bavituximab (formerly Tarvacin) Anti-Phospholipid Therapy Peregrine Phase I Comments: On October 10, 2007, Peregrine announced that it had begun dosing the first patient in a trial of bavituximab for treatment of hepatitis C in people with HIV and hepatitis C coinfection. Peregrine expects to enroll 24 patients in the study. AASLD 2007: In a study of 24 patients who received bavituximab twice weekly in escalating doses based on body weight for two weeks and where the patients were followed another two weeks, it was found that the HCV RNA viral load reductions were in the moderate range of .5 log10. Bavituximab was found to be generally safe and well-tolerated with no dose limiting toxicities or serious side effects reported. (November 18, 2007) A-831 NS5A Inhibitor ArrowTherapeutics Ltd Phase I/II Comments:  A-831 is a NS5A inhibitor that was found (in a test tube) to prevent the HCV IRES-dependent translation process.  A phase I study of A-831 has been initiated in healthy volunteers. In 2007, AstraZeneca acquired Arrow Therapuetics, Ltd. There has been no further news about the development of A-831. (December 12, 2007) NOV-205 Immunomodulator Novelos Therapeutics Phase I Comments: A phase I study has begun to evaluate NOV-205 versus placebo as monotherapy in 18 chronic hepatitis C genotype 1 patients who previously failed treatment with pegylated interferon plus ribavirin. Results from the study found that in the 12 patients treated (6 patients received placebo) there was favorable safety data which has led Novelos to plan a larger study in the second half of 2008. (December 13, 2007) CTS-1027 Anti-inflammatory Conatus Phase II Comments: On December 20, 2007, Conatus announced the initiation of a phase II study of CTS-1027 that will enroll 100 HCV patients for 4 weeks in a proof of concept trial. (December 28, 2007) Oglufanide disodium Immunomodulator Implicit Bioscience Phase II Comments:  A drug that works as a regulator of the body’s immune response has begun testing in hepatitis C positive patients. Two studies are currently underway: 1. phase Ib study of Oglufanide by injection, and 2. an intranasal study. (November 20, 2007) Alinia (nitazoxanide) Thiazolides Romark Laboratories Phase II Comments: EASL 2008:  In a study of 96 treatment-naive and 24 treatment-experienced HCV genotype 4 patients in Eygpt receiving triple therapy of nitazoxanide, pegylated interferon, and ribavirin, 79% achieved an SVR in the treatment-naïve group and 25% in the treatment-experienced group.  In another study that used nitazoxanide monotherapy as a 4 to 12 week lead-in followed by the triple combination (pegylated interferon, ribavirin and mitazoxanide) it was found that the 4 week lead-in resulted in an overall 80% SVR12 (12 weeks post treatment). There were 44 patients in this study and the majority were HCV genotype 4 patients. Currently there are 2 clinical trials using nitazoxanide in combination with pegasys and ribavirin in genotype 1 patients.  STEALTH C-2 will investigate the role of nitazoxanide (plus Pegasys/ribavirin) in 60 genotype 1 prior non-responders to peginterferon/ribavirin therapy.  STEALTH C-3 will investigate nitazoxanide (plus Pegasys/ribavirin) in 60 HCV genotype 1 treatment-naïve patients.  Romark announced on May 21, 2008 that they have completed patient enrollment. (May 22, 2008) SCV-07 Broad spectrum immune stimulator SciClone Phase II Comments: A randomized, placebo-controlled trial of 30 patients (prior treatment genotype 1 relapsers) has been initiated using SCV-07 (injectable) for 7 days to assess the antiviral properties. (June 29, 2007) MitoQ (mitoquinone) Inflammation/ Fibrosis Inhibitor Antipodean Pharmaceuticals Phase II Comments: EASL 2008: In a study to determine if MitoQ reduced necroinflammation in 30 patients with hepatitis C it was found that there was a 26.4% (40 mg dose group) and 28% (80 mg dose group) reduction in ALT levels. The drug was well-tolerated with no significant safety issues reported. (April 29, 2008) DEBIO-025 Cyclophilin inhibitor Debio Pharm Group Phase II Comments: EASL 2008: Results from a double-blind, placebo-controlled study of Debio 025 in combination with Pegasys in HCV genotype 1 and 4 patients vs. treatment with Pegasys monotherapy were released  – total of 90 patients in the study. .  It was found that in the Debio combination arms that there was a 4.6 log10decrease in HCV RNA in the 600 mg/day arm and a 4.8 log10decrease in HCV RNA in 1000 mg/day arm.  This compares to 2.49 log10 in the Pegasys plus placebo arm and 2.20 log10decrease in HCV RNA  in the Debio 1000 mg/day monotherapy arm.   (April 29, 2008) PF-03491390 (Formerly IDN-6556) Pancaspase Inhibitor Pfizer Pharmaceuticals Phase II Comments: Pancaspase 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. The FDA granted Orphan Drug Designation to PF-03491930 for use with organ transplantation in May 2006. Study results of doses ranging from 5 mg to 400 mg daily (given 1 to 3 times a day) in 105 patients (with various liver conditions) for 14 days reported in Hepatology (August 2007) found that there was a significant reduction of ALT and AST levels in all doses except in the lowest dose group. The study authors concluded that longer studies are needed to assess the potential effects of the drug on liver inflammation and fibrosis. (August 2, 2007) Civacir HCV Immune Globulin NABI Phase II Comments: A drug that is believed to prevent the post-transplant recurrence of HCV. Preliminary results show positive safety and pharmacokinetics results. On Feb 1, 2006 the FDA granted fast track designation. Initiation of a phase II ‘Proof of Concept’ clinical trial has begun - the Mayo Clinics in Arizona, Florida and Minnesota have started enrollment. On September 11, 2007 Nabi sold its Biologic strategic business (which includes Civacir) to Biotest AG. The close of the transaction is expected by the end of 2007. (November 22, 2007) MX-3253 (celgosivir) Glucosidase I Inhibitor MIGENIX Phase II Comments:  DDW:  Results from a phase II study of 57 (prior non-responder) patients in 3 treatment combination arms (celgosivir 400 mg/day plus peg-interferon and ribavirin, celgosivir 400 mg plus peg-interferon alone or placebo plus peg-interferon) were released that found that triple therapy produced a substantial decrease in HCV RNA (viral load) compared to peg-interferon plus ribavirin (1.2 log 10 vs. 0.4 log 10). On June 27, 2007 Migenix announced that Schering Plough Corporation would not enter into a period of exclusivity to negotiate terms of a license agreement for celgosivir. In December 2007 Migenix announced the interim results of a study of 10 patients who completed 4-weeks of treatment, and celgosivir was found to be safe and well-tolerated when combined with pegylated interferon plus ribavirin. The study is a 20-patient, 12-week study and results are expected in early 2008. On February 1, 2008 Migenix announced an additional dose of 600 mg (daily) to the study to test for safety and tolerability. (February 10, 2008) VGX-410C (Mifepristone) IRES Inhibitor VGX Pharmaceuticals Phase II Comments: VGX announced on September 2, 2007 that patient enrollment in their multi-site, multi-dose, and double-blind study has been completed. Patients will be treated for 28 days with a 28 day follow-up period. (September 4, 2007) Viramidine (Taribavirin) Nucleoside Analogue Valeant Pharmaceuticals Phase IIb Comments: In two phase III studies viramidine had disappointing rates of effectiveness at the doses given in the clinical trials, but based on the retrospective data of drug exposure in the VISER trials, a new phase 2b study began enrollment of 260 treatment-naïve genotype 1 patients to evaluate taribavirin in doses of 20mg/kg, 25 mg/kg, and 30 mg/kg in combination with pegylated interferon vs. 800-1,400 mg daily ribavirin plus pegylated interferon alfa-2b for 12 weeks.  If the data from 12 weeks of treatment is encouraging, Valeant intends to continue the trial for the full 48-week treatment period with a 24-week follow-up period. Preliminary12 week data from a new Phase IIb study of HCV genotype 1, treatment-naïve patients who received taribavirin at 10mg/kg (67 pts), 25 mg/kg (70 pts),and 30 mg/kg (68 pts) per day found that viral load reductions were similar to the control group of 70 patients who received ribavirin 800-1400 mg daily, but that there was a significantly lower rate of anemia in the taribavirin group.(April 3, 2008) ZADAXIN® (thymalfasin or thymosin alpha 1) Immunomodulator SciClone/Sigma-Tau Phase III Comments: Boosts the immune system.  Patients in a phase III study of Zadaxin used in combination with interferon and ribavirin showed only a modest improvement in treatment outcome and liver histology.  Final results from the complete study released in May 2006 found that Zadaxin in combination with pegylated interferon failed to produce significant results over pegylated interferon alone.  On December 28, 2006 SciClone and its European partner Sigma-Tau announced that full patient enrollment is complete for its phase 3 clinical trial evaluating the use of ZADAXIN® in combination with pegylated interferon alpha and ribavirin to treat patients infected with the hepatitis C virus. This trial is being conducted by Sigma-Tau in Europe and has enrolled a total of 553 patients. Data from this trial are expected to be publicly announced by year-end 2008. (May 23, 2008) Interferons in Development Drug Name Drug Category Pharmaceutical Company Clinical Phase IL-29 (PEG-Interferon Lambda) Long acting Interferon ZymoGenetics Phase I Comments: A phase 1 clinical trial of 20 healthy adults (17 received drug, 3 received placebo) who received one dose of IL-29 has been completed and it was found that the drug was safe and well-tolerated. A larger study in people with HCV (prior treatment-relapsers) is being planned. (December 13, 2007) Oral Interferon alpha Oral Interferon Amarillo Biosciences Phase I Comments: Testing low dose oral administration of alpha interferon absorbed through mucosal membranes. Phase II studies are being planned in cooperation with CytoPharm for the end of 2007. (September 5, 2007) Belerofon (oral) Oral interferon Nautilus Biotech Phase II Comments:  It was announced on May 14, 2007 that the U.S. Food and Drug Administration approved the initiation of a phase I, open-label, ascending study of four doses of oral Belerofon interferon.  According to the company the trial is scheduled to begin in late 2007.  (May 29, 2007) BLX-883 (Locteron) Long Acting Interferon Biolex Therapeutics / OctoPlus Phase II Comments: 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 pegylated interferon). EASL 2008: Results from a Phase 2a, twelve-week study of 32 treatment-naïve HCV genotype 1 patients treated with Locteron (dosed once every two weeks) and ribavirin was released at EASL. In this study the percentage of patients who achieved an early virological response (at least a two-log drop) was 100% (640 & 480 dose groups), 88% (320 dose group) and 37.5% (160 dose group). Locteron was generally well-tolerated with no serious adverse events except one patient in the 640 dose group had an inflammation of the ear which was resolved after treatment was stopped.  (April 29, 2008) Omega Interferon Interferon Intarcia Therapeutics Phase II Comments: Uses an implantable infusion pump that releases a steady amount of Omega interferon for about 1 month. An ongoing Phase II trial is evaluating daily omega interferon alone and in combination with ribavirin in 102 HCV treatment-naïve patients with genotype 1. EASL:  Final results from this study found that 36% of patients who received daily Omega interferon plus ribavirin achieved an SVR compared to 6% who received Omega interferon monotherapy.  The company may study higher doses of Omega interferon.  (April 17, 2007) Albuferon Long Acting Interferon (injections every two weeks) Human Genome Sciences Phase III Comments: On August 28, 2007, HGS announced that the enrollment in the first of the two phase III studies has been completed—ahead of schedule. AASLD 2007: SVR rates for a phase II study of 458 HCV genotype 1 treatment-naïve patients was 58.5 and 55.5 % for patients treated with Albuferon (plus ribavirin) once every two weeks, 50.9% in the Albuferon (plus ribavirin) once every 4 weeks, and 57.9% for the Pegasys (plus ribavirin) group. Another study of 115 prior interferon treatment non-responders treated with various doses of Albuferon plus ribavirin for 48 or 72 weeks resulted in a overall SVR rate of 17.4%. On January 23, 2008 Human Genome Sciences (HGS) announced that, based on the assessment of an independent Data Monitor Committee (DMC), the 1,200-mcg dosing arm of Albuferon is being discontinued due to serious pulmonary (lung) adverse events. The patients in the 1200-mcg will be rolled over to the 900 mcg dosing arm. The company stated that the DMC did not express any safety concerns about the 900-mcg dose of Albuferon. The company also stated that they did not expect the safety concerns would hold up the clinical trial process and they believe that HGS will be able to file for FDA marketing approval in 2009 with a possible 2010 approval date. (January 29, 2008) Consensus interferon (Infergen) Interferon Three Rivers Pharma Phase IV Comments: Infergen is being studied in ongoing clinical trials to establish additional labelling 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.  In December 2006, Valeant announced the initiation of a phase IV study to treat prior pegylated interferon/ribavirin non-responsive patients.  In this study, patients who are being treated with pegylated interferon plus ribavirin and who remain HCV RNA positive at week 12 will be  switched to daily Infergen (15 mcg/day) plusribavirin (1.0-1.2 g/day) for 36 or 48 weeks or continue on their pegylated interferon and ribavirin regimen for an additional 36 weeks of therapy.  On December 20, 2007, it was announced that Valeant sold Infergen to Three Rivers Pharmaceuticals. (December 28, 2007)   Vaccines in Development Drug Name Drug Category Pharmaceutical Company Clinical Phase ChronVac-C DNA-based Therapeutic Vaccine Inovio / Tripep Phase I Comments: Tripep AB of Sweden has received approval from the Swedish Medical Products Agency to initiate a phase I/II clinical trial. Twelve HCV positive patients will be enrolled to study the safety, immune boosting and antiviral properties of this therapeutic vaccine. On November 27, 2007 Inovio announced that it had started the treatment of ChonVac-C to the first patient enrolled in their trial. Preliminary results from the first 5 patients treated showed no safety issues. On June 30, 2008 Inovio released prelimary data on the first two patients and it showed that during and after treatment HCV RNA levels decreased up to 87% and 98% respectively. (July 1, 2008) TG4040 Therapeutic Vaccine Transgene Phase I Comments: On Oct 01, 2007 Transgene announced that the first patient of an expected 24 HCV-positive patients was enrolled in a study being conducted in Canada. On 2/13/2007 Transgene announced that it had begun enrollment in France of chronic HCV patients and that it will enroll a total of 15 patients to study the safety, tolerability, virological and immunological response of TG4040. Preliminary data was reported on May 19th, 2008 and it was found that the drug was safe and well-tolerated and that six out of 15 patients experienced a viral load reduction ranging from .05 to 1.4 log10. (May 21, 2008)     PeviPROTM Therapeutic vaccine Pevion Biotect Phase I  Comments: On December 18, 2006, Pevion Biotech announced the start of a phase I clinical trial in 30 healthy volunteers to test the safety and tolerability of the synthetic vaccine. The secondary objective is to assess the immunogenicity of the vaccine. The study is scheduled for completion by the end of 2007. (September 4, 2007) HCV/MF59 Vaccine(s) Chiron / Novartis 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 received 4 different doses of vaccine and that all produced HCV antibodies .  The study is on-going.  (May 2, 2008)   GI-5005 Therapeutic Vaccine Globe Immune Phase II Comments:  A form of therapeutic vaccine that is believed to stimulate the immune system to help fight HCV. AASLD 2007: A Phase 1b double-blinded, placebo controlled, dose-escalating, multi-center trial evaluating the safety, immunogenicity, and efficacy of GI-5005 found that 11% of patients receiving GI-5005 had viral load reductions from -0.75 to 1.4 log10 and that dose response for ALT normalization reached 50% in the group receiving the highest dose (40 YU). GI-5005 was well-tolerated with no dose limiting toxicities. A Phase 2b trial is being initiated comparing the triple therapy of GI5005, pegylated interferon, and ribavirin to the dual therapy of pegylated interferon and ribavirin. On December 19, 2007, GlobeImmune announced the initiation of a phase II study expected to enrol 120 patients who will receive Tarmogen in combination with pegylated interferon plus ribavirin and compare the triple to regular standard of care (peg with ribavirin). On May 20, 2008 GlobeImmune announced that it had completed enrollment of the trial.  (May 21, 2008) 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). Data released in December 2006 found a good safety profile of IC41 when used in combination with pegylated interferon and ribavirin. The study did not find a statistical improvement in relapse rate of the patients given IC41, but according to Intercell the doses were sub-optimal. An ongoing proof of concept study to assess the effectiveness of IC41 at an optimal dose is currently underway. The interim data from the first 25 patients found that there were statistically significant viral load reductions and a very good safety profile. The full study results from 50 patients are expected in the first quarter of 2008. On February 7, 2008 Intercell announced that interim results found that in 50 patient treated with IC41 there was an average of 60% viral load reductions. (February 10, 2008)   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 trial will enroll 41 patients with advanced liver cancer using GV1001 in combination with GM-CSF (stimulates the production of neutrophils or white blood cells). On November 19, 2007, Pharmexa released interim data on 21 patients in the trial—all six vaccine doses were well-tolerated and no vaccine-attributable serious adverse events were observed. No tumor responses were observed in any of the 21 patients, but the measurable response data will not be available until the second quarter of 2008. (November 21, 2007) PI-88 Anti-liver cancer Progen Industries Phase II Comments:  A treatment for primary liver cancer following surgical resection of a liver tumor. Final results from the phase II clinical trial found that the 160 mg dose was well-tolerated and increased the disease free state (liver cancer) of 25% of the patients and prolonged the time to tumor recurrence from 27 to 48 weeks (78%). Progen estimates that phase III clinical trials will begin at the end of 2007. The U.S. FDA granted Fast Track status and the commission of the European Communities has granted orphan product designation. (October 1, 2007) Nexavar (sorafenib) Anti-liver cancer Onyx Pharmaceuticals  Phase III FDA Approved Comments: In two clinical trials 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 expedited and the FDA will take action within six months of the date on which the FDA received the application. On November 19, 2007 Bayer AG announced that Nexavar had been approved by the FDA for the treatment of hepatocellular carcinoma (HCC), which is the most common form of liver cancer. (November 21, 2007) ThermoDox (doxorubicin) Anti-liver cancer Celsion  Phase III Comments: Phase one interim results found that ThermoDox (doxorubicin) – heat-activated liposome therapy – in combination with Radiofrequency Ablation of primary and metastatic tumors to the liver showed local return of cancer in only 2 of 44 tumors resulting in a 4.5% local recurrence rate. Also, 5 of the 10 evaluable patients demonstrated a complete response along with a single partial response. The company also announced a new phase III trial of Doxorubicin in patients with hepatocellular carcinoma (HEAT study). (July 3, 2008)   Adjunct Therapies Drug Name Drug Category Pharmaceutical Company Clinical Phase LGD-4665 Thrombopoeitin Receptor Agonist Ligand Pharmaceuticals Inc. Phase I Comments: A phase I study that evaluated LGD-4665 in multiple doses over 14 days found that it was safe and well-tolerated and produced an increase in platelet counts in the single and multiple daily dose regimens. (December 28, 2007) Eltrombopag (Promacta) Thrombopoeitin Receptor Agonist GlaxcoSmithKline Phase II Comments: A recent study found that eltrombopag boosted platelet counts in a majority of patients at each of three dosage levels and the patients were able to continue or start HCV treatment. On December 20, 2007, GSK announced that they had applied for FDA approval to market eltrombopag for short term treatment of chronic idiopathic thrombocytopenic purpura (ITP) (December 28, 2007)   Drugs  on Hold Drug Name Drug Category Pharmaceutical Company Clinical Phase JBK-122 Anti-inflamatory Jenken Biosciences Phase II Comments: The FDA approved JBK-122 for Phase II clinical studies. The drug jumped into Phase II studies since the safety of JBK-122 had already been studied in humans. The goal of the study is to treat or prevent liver damage caused by HCV-related inflammation. (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 disease progression to assess progression of liver cancer.  Doxorubicin Transdrug has been granted orphan drug status by the EMEA (Europe) and FDA (United States). (December 16, 2006) Although there was shown to be a clinical benefit, there were also more frequent and more severe pulmonary adverse events than expected. Based on this the trial has been suspended. (July 16, 2006)   Clinical trials that have been cancelled Drug Name Drug Category Pharmaceutical Company Clinical Phase Heptazyme RNA Inhibitor RPI Studies Cancelled Levovirin Nucleoside Analogue Valeant Pharmaceuticals Studies Cancelled Interleukin-10 Anti-fibrotic Schering-Plough Studies Cancelled HCV-086   ViroPharma / Wyeth Studies Cancelled R803 Non-nucleoside HCV Polymerase Inhibitor Rigel Pharmaceuticals Studies Cancelled IP-501 Anti-fibrotic Indevus Studies Cancelled VX-497 (Merimebodib) IMPDH Inhibitor Vertex Studies Cancelled BILN 2061 Serine Protease Boehringer - Ingelheim Studies Cancelled SCH-6 Serine Protease Schering Studies Cancelled ANA245 Isatoribine Anadys Studies Cancelled Rituximab Anti-CD20 Monoclonal Antibody Genetech/IDEC Studies Cancelled JTK 003 Polymerase Inhibitor Akros Pharma Studies Cancelled ISIS 14803 Antisense Isis Pharma Studies Cancelled Ceplene Histamine EpiCept Studies Cancelled Interferon gamma-1b Anti-fibrotic InterMune Studies Cancelled ANA971 Isatoribine Anadys Studies Cancelled CPG 10101 (Actilon) Immunomodulator Coley Studies Cancelled GS9132/ACH806 Protease Inhibitor Gilead/Achillion Studies Cancelled XTL-2125 Polymerase Inhibitor XTL Biopharmaceuticals Studies Cancelled ANA975 Isatoribine Anadys Studies Cancelled AVI-4065 Antisense Compound BioPharma Studies Cancelled UT-231B Imino Sugar Inhibitor United Therapeutics Studies Cancelled G1262570 Anti-fibrotic GlaxoSmithKline Studies Cancelled EMZ702 Interferon Enhancer Transition Therapeutics, Inc Studies Cancelled Interferon beta-1a (REBIF) Interferon Ares-Serono Studies Cancelled INNO0101 (E1) Therapeutic Vaccine Innongenetics Studies Cancelled Amantadine Broad Antiviral Endo Labs Solvay Studies Cancelled R7025 (MAXY-alpha) Pegylated interferon Maxygen/Roche Studies Cancelled NM283 (Valopicitabine) Polymerase Inhibitor Idenix Pharmaceuticals Studies Cancelled HCV-796 Polymerase Inhibitor ViroPharma/Wyeth Studies Cancelled HCV-AB68 Monclonal Antibody XTL Bio Studies Cancelled XTL-6865 (formerly HepX-C) Monclonal Antibody XTL Bio Studies Cancelled Suvus (Mehylene blue) formerly BIVN-401 (Virostat) Antiviral Genzyme Oncology Studies Cancelled Hepaconda Bezafibrate Giaconda 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)   About Clinical Trials 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 or very near to 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. 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 evaluate safety, optimal dose, and may include some information on the drug's effectiveness. 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. Fast Track Status: A drug can be granted fast track status by the Food and Drug Administration to help facilitate the development and to expedite the review process of new drugs that have the potential to address an unmet medical need for serious or life-threatening conditions such as hepatitis C. For an overview of the latest on drug development from AASLD 2007 click here. Orphan Drug Status: A status given to a certain drug by the Food and Drug Administration to encourage the development of drugs that are necessary, but are too expensive or unprofitable to develop under regular circumstances. Drugs being developed to treat orphan diseases (low prevalence in the population) offer tax reductions and marketing exclusivity for the drug manufacturer (up to 20 years). For more information about clinical trials for the treatment of hepatitis C go to www.clinicaltrials.gov Back to Hepatitis C About Hepatitis | News Updates | Community & Support | Resource Library | About HCSP | Contact Us | Site Map | Resources en Español | Home (C) 2008. Hepatitis C Support Project