Hepatitis C Treatments in Current Clinical Development

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Hepatitis C Treatments in Current Clinical Development

Updated January 6, 2011

How to use the new HCV Advocate HCV Drug Pipeline:

The current page will list only HCV Direct-Acting Antivirals (DDAS). The first section is the Quick Reference Guide. You can click on the label “Company†and it will link you directly to the company that is developing the drug. Phase I studies will not include any additional information—except for DAAs. Phase 2 and Phase 3 studies will include a short recap or comments of the clinical trial results. You can access the comments by clicking on the “Drug Name.â€

The drugs that are being developed that are not DAA drugs can be accessed by clicking on the “Drugs in Development – General†link below this note. We will not include comments in this section unless the drug has advanced into a Phase 3 or Phase 4 study.

In addition we have various educational materials below to help explain some of the clinical trial processes and help with interpreting clinical trial data.

Drugs in Development - Direct-Acting Antivirals (DAA)

Drugs in Development - General

Clinical Trial Process: Making Sense of Clinical Trials

How to Read an Abstract

Cancelled Trials

To locate clinical trials go to www.clinicaltrials.gov – type in HCV or hepatitis C and drill down to studies that are listed by this resource.

Quick Reference Guide

Phase I

Drug Name

Drug Category

Company

ABT-072

Polymerase Inhibitor

Abbott

ABT-333

Polymerase Inhibitor

Abbott

ABT-450

Protease Inhibitor

Abbott / Enanta

AZD-7295

NS5A Inhibitor

AstraZeneca

BMS-824383

NS5A Inhibitor

Bristol-Myers Squibb

Clemizole

NS4B Inhibitor

Eiger BioPharmaceuticals

IDX375

Polymerase Inhibitor

Idenix

INX-189

Polymerase Inhibitor

Inhibitex

MK-3281

Polymerase Inhibitor

Merck

PPI-461

NS5A Inhibitor

Presidio

PSI-7851

Polymerase Inhibitor

Pharmasset

PSI-938

Polymerase Inhibitor

Pharmasset

VX-500

Protease Inhibitor

Vertex

VX-916

Polymerase Inhibitor

Vertex

Note: Only drugs that have advanced into phase 2 and 3 studies will include comments

DAA Combinations

Drug Name/Category

Drug Name/Category

Company

Phase / Updated

ABT-450 Protease Inhibitor

ABT-072 Polymerase Inhibitor

Abbott

Phase II Jan 6, 2011

BI 201335 Protease Inhibitor

BI 207127 Polymerase Inhibitor

Boehringer Ingelheim Pharma

Phase II Nov 11, 2010

BMS 790052 (NS5a Inhibitor)

BMS 65032 (Protease Inhibitor)

Bristol-Myers Squibb

Phase II Nov 11, 2010

GS-9256

GS-9190 (Tegobuvir)

Gilead

Phase II Nov 11, 2010

PSI-7851 Polymerase Inhibitor

PSI938 Polymerase Inhibitor

Pharmasset

Phase IDec 8, 2010

RG7128 (Polymerase Inhibitor)

RG7227(Danoprevir) Protease Inhibitor

Genentech / Pharmasset

Phase II Nov 11, 2010

Telaprevir (Protease Inhibitor)

VX-222 (Polymerase Inhibitor)

Vertex

Phase II Nov 11, 2010

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Phase 2

Drug Name

Drug Category

Company

Updated

ACH-1625

Protease Inhibitor

Achillion

Oct 2 , 2010

ANA598

Polymerase Inhibitor

Anadys Pharmaceuticals

Jan 6, 2011

BI 201335

Protease Inhibitor

Boehringer Ingelheim Pharma

April 29, 2010

BI 207127

Polymerase Inhibitor

Boehringer Ingelheim Pharma

June 29, 2010

BMS 650032

Protease Inhibitor

Bristol-Myers Squibb

Nov 11, 2010

BMS 790052

NS5A Inhibitor

Bristol-Myers Squibb

Nov 11, 2010

BMS 791325

Polymerase Inhibitor

Bristol-Myers Squibb

Sep 30, 2010

Filibuvir

Polymerase Inhibitor

Pfizer

June 30, 2010

GS 9190 (Tegobuvir)

Polymerase Inhibitor

Gilead

Nov 11, 2010

GS-9256

Protease Inhibitor

Gilead

Nov 11, 2010

PSI-7977

Polymerase Inhibitor

Pharmasset

Jan 6, 2011

RG7128

Polymerase Inhibitor

Pharmasset / Genentech

Nov 11, 2010

RG7227 (Danoprevir)

Protease Inhibitor

InterMune / Genentech

Nov 11, 2010

SCH900518 (Narlaprevir)

Protease Inhibitor

Merck

June 29, 2010

TMC435

Protease Inhibitor

Medivir / Tibotec

Nov 23, 2010

Vaniprevir (MK-7009)

Protease Inhibitor

Merck

Nov 11, 2010

VX-222

Polymerase Inhibitor

Vertex

Nov 23, 2010

VX-759

Polymerase Inhibitor

Vertex

March 12, 2009

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Phase 3

Drug Name

Drug Category

Company

Updated

Boceprevir

Protease Inhibitor

Merck

Jan 6, 2011

Telaprevir

Protease Inhibitor

Vertex

Jan 6, 2011

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ABT-450/rHCV Protease Inhibitor (with ritonavir)

ABT-072 Polymerase Inhibitor

Abbott

Jan 6, 2011

Comments: The combination of ABT-450 (combined with ritonavir), ABT-072 and ribavirin will be given to HCV genotype 1 treatment-naïve patients for 12 weeks. Patients will be followed for an additional 48 weeks after completion of study.

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BI 201335 Protease Inhibitor

BI 207127Polymerase Inhibitor

Boehringer Ingelheim Pharma

Nov 11, 2010

Comments: AASLD 2010: In a study (without interferon) the triple regime of BI 201335 (protease inhibitor) plus BI 207127 (polymerase inhibitor) and ribavirin to treat HCV genotype 1 treatment-naïve patients was found to provide strong antiviral activity—additional studies with longer durations are planned to evaluate sustained virological response rates.

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BMS 790052 NS5A Inhibitor

BMS 65032 Protease Inhibitor

Bristol-Myers Squibb

Nov 11, 2010

Comments: In an important study the combination of BMS-650032 (protease inhibitor) and BMS-790052 was given to genotype 1 null-responders to a prior course of therapy. The interim results at 12 weeks (total study duration is 24 weeks) produced early antiviral activity, but 6 out of the 11 people treated had viral breakthrough indicating that pegylated interferon and/or ribavirin will be needed to completely suppress the virus at least in this study. When the combination was combined with pegylated interferon and ribavirin 9 out of 10 patients became HCV RNA undetectable by week 12.

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GS-9256(Protease Inhibitor)

GS-9190(Tegobuvir)Polymerase Inhibitor

Gilead

Oct 11, 2010

Comments: In a study that included many doses and arms it was found that the combination of GS-9256 (HCV protease inhibitor) plus tegobuvir (GS-9190 – polymerase inhibitor) when combined with pegylated interferon plus ribavirin produced the best results. In the group that was given quadruple therapy for 4 weeks followed by 44 weeks of pegylated interferon plus ribavirin, 14 out of 14 patients were HCV RNA negative by day 28. There is an ongoing 4 month study of the quadruple therapy.

PSI-7851 Polymerase Inhibitor

PSI938 Polymerase Inhibitor

Pharmasset

Dec 8, 2010

Comments: Phase 1 combination study to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously. The antiviral properties of the drugs (alone and in combination) will be observed for 14 days.

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RG7128 (Polymerase Inhibitor)

RG7227 (ITMN-191) (Danoprevir) Protease Inhibitor

Vertex

Oct 11, 2010

Comments: On March 2, 2010 Vertex announced the initiation of a phase II trial of telaprevir/VX-222 (2 arms with and 2 arms without pegylated interferon/ribavirin). There 4 treatment arms will include 25 patients in each arm. The treatment duration (12 weeks, 36 weeks) will be guided by response at certain time points during the trial.

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Telaprevir (Protease Inhibitor

VX-222 (Polymerase Inhibitor)

Genentech /Pharmasset

Oct 11, 2010

Comments: EASL 2010: A small study using ritonavir (100 mg) to boost danoprevir (200 mg) both given twice a day achieved 100% undetectable HCV RNA after 15 days and was generally well-tolerated. Based on these findings an additional two study arms of prior complete non-responders will be retreated with danoprevir, ritronavir, PEG/RBV for 12 weeks. A larger study titled INFORM-3 is being planned that will include ritonavir. On October 7th, 2010, Genentech announced that it had purchased the full rights to Danoprevir from InterMune.

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ACH-1625

Protease Inhibitor

Achillion

Oct 2, 2010

Comments: Results from two small studies (9 pts and 8 pts) treated with 200 or 600 mg for 5 days had a 3.86 and 3.81 log10 viral load decline respectively. Adverse events were classified as mild to moderate. Recently, Achillion announced a placebo-controlled phase IIa study to evaluate the safety, tolerability and antiviral activity of ACH-1625 in conjunction with pegylated interferon alfa-2a and ribavirin. The study will evaluate HCV genotype 1 patients after 4 and 12 weeks of dosing. The results from the 4 week study are expected in the first quarter of 2011, and the 12 week study results are anticipated by the end of 2011.

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ANA598

Polymerase Inhibitor

Anadys Pharmaceuticals

Jan 6, 2011

Comments: There is an ongoing study of ANA598 (in multiple doses) combined with pegylated interferon plus ribavirin. 29 HCV genotype 1 treatment-naïve patients received the triple therapy for 12 weeks and were randomized (depending of treatment response) to an additional 12 or 36 weeks. The SVR 12 results in the patients who completed 24 weeks of treatment was 73% (in eight patients). The most common side effect was rash and it was observed in 59% of the patients who received the 400 mg dose. On January 4, 2011 Anadys announced that an additional study was being initiated in 200 HCV genotype 1 treatment- naïve and treatment-experienced patients.

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BI 201335

Protease Inhibitor

Boehringer Ingelheim Pharma

April 29, 2010

Comments: EASL 2010: The results from the SILEN-C2 study of 280 HCV genotype 1 patients who were prior non-responders treated for 24 weeks with either 240mg BI 201335 (once-a-day), 240 mg BI 201335 (once-a-day) after a 3-day lead-in of PEG/RBV or 240 BI 201335 (twice-a-day) after a 3-day lead-in period of PEG/RBV. After 24 weeks of treatment the participants were continued on PEG/RBV for an additional 24 weeks. Interim results found at week 12 reported that 54 to 59% were HCV RNA undetectable (less than 10 IU/mL). The majority of people who discontinued treatment were in the BI twice- a-day group (24%) compared to 4% in the once-a-day groups. The combination of BI 201335 and BI 20127 is being studied (see DDA combinations).

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BI 207127

Polymerase Inhibitor

Boehringer Ingelheim Pharma

June 29, 2010

Comments: In a 5-day monotherapy study of HCV genotype 1 patients reported a median 3.8 log10 viral load decrease. The combination of BI 201335 and 20127 is being studied (see DDA combinations).

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BMS 650032

Protease Inhibitor

Bristol-Myers Squibb

Nov 11, 2010

Comments: AASLD 2010: In a study (without interferon) the triple regime of BI 201335 (protease inhibitor) plus BI 207127 (polymerase inhibitor) and ribavirin to treat HCV genotype 1 treatment-naïve patients was found to provide strong antiviral activity—additional studies with longer durations are planned to evaluate sustained virological response rates.The combination of BMS 650032 and BMS 790052 are being studied (see DAA combinations).

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BMS 790052

NS5A Inhibitor

Bristol-Myers Squibb

Sep 30, 2010

Comments: BMS 790052 is being given once a day for 12-24 weeks with pegylated interferon and ribavirin or for 24 or 48 weeks guided by on-treatment response. There are various separate studies of BMS 790052 being conducted in HCV genotype 1 treatment-naïve, non-response and treatment-intolerant patients. A study of 48 HCV genotype 1 treatment-naïve patients treated with various doses of BMS 790052 in combination with pegylated interferon plus ribavirin for 48 weeks has been completed and data is expected to be released in 2010-2011. BMS 790052 is also being studied in combination with BMS 65032 (see DAA combination above).

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BMS 791325

Polymerase Inhibitor

Bristol-Myers Squibb

September 30, 2010

Comments: A new trial will evaluate the safety, tolerability and efficacy of BMS 791325 in combination with pegylated interferon in HCV genotype 1 treatment-naïve patients. Treatment duration (4 to 48 weeks) will be guided by on-treatment response.

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Filibuvir

Polymerase Inhibitor

Pfizer

June 30, 2010

Comments: EASL 2010: Study results from 35 patients who were treated with filibuvir, pegylated interferon and ribavirin found that 75% were HCV RNA negative after 4 weeks of treatment.

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GS 9190(Tegobuvir)

Polymerase Inhibitor

Gilead

Nov 11, 2010

Comments: AASLD 2010: A study of HCV genotype 1 treatment naïve patients in single and multiple doses found HCV RNA reductions ranging for -1.22 to -1.95 log10. The combination of GS 9190 and GS9256 are being studied (see DAA Combinations above).

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GS 9256

Protease Inhibitor

Gilead

Nov 11, 2010

Comments: EASL 2010: Results from a three day 6-arm safety and dose-ranging study of 54 HCV genotype 1 treatment-naïve patients was released. It was found that GS-9256 was safe and generally well-tolerated and showed dose dependant antiviral activity. Phase II studies of GS-9256 with or without ribavirin are underway. (April 29, 2010)The combination of GS 9190 and GS9256 are being studied (see DAA Combinations above).

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PSI-7977

Polymerase Inhibitor

Pharmasset

Jan 6, 2011

Comments: AASLD 2010: PSI-7977, a polymerase inhibitor, dosed once a day (100, 200 and 400 mg) combined with pegylated interferon plus ribavirin for 28 days produced 4 week RVRs of 88 to 94% compared to 21% in the pegylated interferon plus ribavirin group (without PSI-7977). At week 12 the cEVR (complete early virological response) was highest in the 200 mg QD (94%) and 400 (87%) compared to 64% cEVR in the pegylated interferon plus ribavirin (placebo) group. Based on these results a 12 week study is being planned. In addition PSI-7977 appears to work against different genotypes.On December 14, Pharmasset anounced the commencement of an exploratory study, The trial will evaluate PSI-7977 400mg QD in combination with ribavirin , with 0, 4, 8, or 12 weeks of pegylated interferon alfa 2a in treatment-naive patients infected

with HCV genotype 2 or 3. About 40 patients infected with HCV genotype 2 or 3, not been previously treated are expected to be enrolled. The primary endpoint of the trial will be the assessment of safety and tolerability of PSI-7977 400mg QD and RBV for 12 weeks, administered with or without pegylated interferon in treatment naïve patients with HCV genotypes 2 or 3. On January 6, 2011 Pharmasset announced preliminary results of a trial of 24 HCV genotype 2 and 3 patients who received PSI-7977 (with Pegylated interferon plus ribavirin) for 12 weeks—total treatment duration. All patients were HCV RNA negative at the end of the treatment period and are being followed to assess SVR12 and SVR 24.

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RG7128

Polymerase Inhibitor

Pharmasset / Genentech

Nov 11, 2010

Comments: AASLD 2010: RG7128 (500 or 1000 mg - BID) combined with pegylated interferon plus ribavirin was given in different doses and time lines based on response and it was found that RG7128 was safe and well-tolerated in HCV genotype 1 and 4 treatment-naïve patients with and without cirrhosis. The group that received the 8 or the 12 week regime of 1000 mg BID achieved the highest declines in HCV RNA (viral load) levels. RG7128 appears to have a high barrier to drug resistance.

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RG7227 (Danoprevir)

Protease Inhibitor

InterMune / Genentech

Nov 11, 2010

Comments: AASLD 2010: Interim results using various doses of danoprevir combined with pegylated interferon plus ribavirin found that 88 to 92% were HCV RNA negative by week 12 compared to 43% in the placebo group. More studies are planned including a study using ritonavir as a boosting agent.

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SCH900518 (Narlaprevir)

Protease Inhibitor

Merck

June 29 , 2010

Comments: EASL 2009: A study of 40 genotype 1 patients (treatment- naïve; treatment-experienced) who received ritonavir-boosted narlaprevir, pegylated interferon/ ribavirin or placebo (with pegylated interferon/ribavirin) found an 81% SVR in the treatment- naïve group; the SVR results in the treatment-experienced were similar between the narlaprevir and placebo groups.

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TMC435

Protease Inhibitor

Medivir / Tibotec

Nov 23, 2010

Comments: AASLD 2010: Interim results from a study of TMC435 (75 and 150 mg QD (once a day)) combined with pegylated interferon plus ribavirin given to HCV genotype 1 treatment-naïve patients for up to 24 weeks showed that TMC435 produced significant viral load reductions. In patients who completed 24 weeks treatment or stopped treatment for any reason by week 24 the SVR results ranged from 88 to 97% (119 out of 130 patients). So far there is a low rate of viral breakthrough.Interim 24 week results from a study of prior HCV genotype 1 treatment experienced patients found that 78 to 94% were HCV RNA undetectable. Tibotec is expected to begin phase III clinical trials in the first half of 2011.

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Vaniprevir(MK-7009)

Protease Inhibitor

Merck

Nov 11, 2010

Comments: AASLD 2010: A study of 45 HCV genotype 1 treatment-naïve patients who were administered 1 of 5 regimens—placebo, 300 mg BID (twice a day), 600 mg BID, 600 mg QD (once a day) or 800QD in combination with pegylated interferon plus ribavirin for 4 weeks followed by an additional 44 weeks of pegylated interferon plus ribavirin resulted in SVR rates of 78 to 84% compared to 63% in the placebo (only pegylated interferon and ribavirin). Note: the high SVR rate in the placebo group is likely due to the small patient population in this group.

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VX-222

Polymerase Inhibitor

Vertex

Nov 23, 2010

Comments: EASL 2010: The results from a small study of 32 HCV genotype 1 treatment-naïve patients treated with various doses of VX-222 (250, 500 and 750 twice-a-day; 1500 mg once-a-day) found a viral load reduction of -3.1 to 3.4 log10 IU/mL) by day 4 of treatment. VX-222 was generally safe and well-tolerated.

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VX-759

Polymerase Inhibitor

Vertex

March 12, 2009

Comments: In a 10 day phase I study in which 32 treatment- naïve HCV patients received different doses of VX-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 VX-759 is underway. Additional studies will combine VX-759 and other DAAs. VX-759 is considered to be a back-up drug to VX-222.

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Boceprevir

Protease Inhibitor

Merck

Jan 6, 2011

Comments: On January 6, 2011 Merck announced that it had submitted a market application to the Food and Drug Administration in the U.S.and to the European Union and was accepted for expedited review. Approval is expected mid-2011.See the HCSP Factsheet:

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Telaprevir

Protease Inhibitor

Vertex

Jan 6, 2011

Comments:On November 22, 2010 Vertex announced that they had completed submission of their data to the Food and Drug Administration and requested a 6 month priority review. On December 20, 2010, Janssen-Cilag ( & in Europe) will seek approval from the European Medicines Agency (EMA) for a new investigational treatment for the chronic genotype 1 hepatitis C virus (HCV). JNJ owns the commercial rights to Telaprevir in Europe. See the HCSP Factsheet:Tibotec/Vertex have begun a phase III study to evaluate telaprevir dosed twice daily or 3 times a day (combined with pegylated interferon, and ribavirin).

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