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New HCV Drugs at AASLD
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from Jules: below are links to key data reports on the many new oral HCV drugs at various stages of development and there are numerous drugs in development from the various new classes which include protease inhibitors, polymerase inhibitors (nucleosides, nucletides, various types of NNRTIs), NS5A inhibitors, and if pegIFN must be used there is peg-lambda IFN. Of course Vertex & Merck presented phase 3 data results at AASLD but also there were many data updates from the other drugs in earlier stages of development. Response-Gulded Therapy (RGT) will be the new mantra in HCV therapy once the 1st oral drugs hit the market and this means patients & clinicians must bring in patients at time-checks early after starting therapy to see if viral load is undetectable or not; these time-point checks to decide if a patient should continue or stop therapy, and I see this concept continuing to be refined over time, we will move towards 16 week or even 12 week total therapy as we improve regimens to include 3 or 4 orals with or without peg/rbv.
In the Vertex large phase 3 ADVANCE Study of the HCV protease inhibitor telaprevir, which included over 1000 genotype 1 treatment-naïve patients presented at AASLD, study patients who received telaprevir plus Pegasys/rbv had a significantly higher SVR (Sustained Viral Response, cure): 75% vs 44% of patients who received just Pegasys/rbv. These numbers included patients who had either 24 or 48 weeks total therapy. Patients, both blacks and whites, who had undetectable viral load at the early time-checkpoints, weeks 4 and 12, about 90% achieved SVR. In the Merck SPRINT-2 phase 3 Study of boceprevir presented at AASLD, over 1000 genotype 1 treatment-naïve patients participated, patients received either boceprevir plus Pegintron/rbv or just Pegintron/rbv, with 67-71% of non-Blacks achieving a SVR (cure) vs 40% for study patients who received Pegintron/rbv, and 42-53% of Blacks achieving cure vs 23% who received only Pegintron/rbv, these results were for patients who had a total duration of therapy of 24 or 48 weeks. An undetectable viral load at the early time-check-points in this study, weeks 8 and 24, also achieved high rates of SVR, cure.
How much affect on outcome (SVR) will IL28B and the genotype 1a vs 1b have once oral therapy are added to peg/RBV remains to be seen, but certainly as you add more than 1 oral to peg/rbv their impact will diminish & eventually be minimal or disappear altogether. BMS presented the early data, the 1st data in null-responders receiving 2 orals only or 2 orals plus peg/rbv, the results from this study were highly anticipated and begin to give us important information on treatment without peg/rbv but also in treating null-responders, as all 10 null-responders had undetectable viral load after 12 weeks with all 4 drugs. After initial monotherapy ABT-450 looked very potent, perhaps a 6-log drug. The nucleoside polymerase R7128 shows good 12 week data underscoring the importance that this drug or class appears not be associated with resistance developing easily & early, and this is important. Pharmasset presented data on 2 nucleotides with potency & also the possibility of not be associated with resistance developing. The BMS NS5A is potent. Some drugs are administered once daily, some three times daily, the side effects profiles differ between the drugs, and success with therapy will require management of side effects, like anemia. The data from both Vertex & Merck show that African-Americans can have response rates as high as whites if they have early RGT results, that is if the viral load is undetectable at the early-time-points the cure or SVR rates are equally high for blacks, latinos and whites.
AASLD: New HCV Drugs at AASLD, easy to understand report: (see links below to reports from AASLD) - (11/10/10)
AASLD: Genotype 1b vs 1a and Peg/Rbv Lead-In - (11/12/10)
AASLD: Telaprevir Resistance Disappears in 89% of Patients: Long-Term Follow-up of Patients with Chronic Hepatitis C Treated with Telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin: Interim Analysis from the EXTEND Study - (11/16/10)
AASLD: Telaprevir in Combination with Peginterferon alfa-2a and Ribavirin in Genotype 1 HCV Treatment-Naïve patients: Final results of Phase 3 ADVANCE Study - (11/03/10)
AASLD: Phase 3 - Response Guided Therapy (RGT) - Boceprevir Combined with peginterferon alfa-2b plus ribavirin for treatment-naïve patients with HCV genotype 1 (SPRINT-2 Final Results) - (11/03/10)
AASLD: No evidence of drug resistance or baseline S282T resistance mutation among GT 1 and GT 4 HCV infected patients on nucleoside polymerase inhibitor RG7128 and Peg-IFN/RBV combination treatment for up to 12 weeks: Interim analysis from the PROPEL study - (11/21/10)
AASLD: Combination Therapy With BMS-790052 and BMS-650032 Alone or With Pegylated Interferon and Ribavirin (pegIFN/RBV) Results in Undetectable HCV RNA Through 12 Weeks of Therapy in HCV Genotype 1 Null Responders - (11/03/10)
AASLD: 5 New Potent HCV Protease inhibitors - (11/05/10)
AASLD: Low rate of viral load rebound observed among treatment-naive genotype 1 patients with chronic hepatitis C treated with danoprevir (RG7227) plus Peg-IFN α-2a (40KD) (PEG ASYS) plus ribavirin: interim analysis - (11/21/10)
AASLD: New HCV Drugs: R7128 nucleoside, PSI7977 nucleotide, PSI938 nucleotide, ANA598 nnrti (rash), danoprevir protease, IMO-2125, a TLR agonist - (11/05/10)
AASLD: High Rapid Virologic Response (RVR) with PSI-7977 Daily Dosing plus PEG-IFN/RBV in a 28-day Phase 2a Trial - (11/08/10)
AASLD: 4-Week Virologic Response and Safety of ABT-450 Given with Low-dose Ritonavir (ABT-450/r) First As 3-Day Monotherapy Then in Combination with Pegylated Interferon Alpha-2a and Ribavirin (SOC) in Genotype 1 (GT1) HCV-infected Treatment-naïve Subjects - (11/02/10)
AASLD: Initial Antiviral Activity of the HCV NS3 Protease Inhibitor ABT-450 When Given with Low-dose Ritonavir as 3-Day Monotherapy: Preliminary Results of Study M11-602 in Genotype 1 (GT1) HCV-infected Treatment-naïve Subjects - (11/08/10)
AASLD: BMS-790052, a First-in-Class Potent Hepatitis C Virus NS5A Inhibitor, Demonstrates Multiple-Dose Proof-of-Concept in Subjects With Chronic GT1 HCV Infection (potent, up to 5.7 log reduction) - (11/10/10)
AASLD: Pegylated Interferon Lambda (pegIFNλ) Phase 2 Dose-Ranging, Active-Controlled Study in Combination With Ribavirin (RBV) for Treatment-Naive HCV Patients (Genotypes 1, 2, 3, or 4): Safety, Viral Response, and Impact of IL28B Host Genotype Through Week 12 - (11/08/10)
AASLD: Sustained Viral Response (SVR) Rates in Genotype 1 Treatment-naïve Patients with Chronic Hepatitis C (CHC) Infection Treated with Vaniprevir (MK-7009), a NS3/4a Protease Inhibitor, in Combination with Pegylated Interferon Alfa-2a and Ribavirin for 28 Days - (11/04/10)
AASLD: New HCV Drugs: R7128 nucleoside, PSI7977 nucleotide, PSI938 nucleotide, ANA598 nnrti (rash), danoprevir protease, IMO-2125, a TLR agonist - (11/05/10)
AASLD: Pharmacokinetics, Safety, and Tolerability of PSI-352938, a Novel Nucleotide Polymerase Inhibitor for HCV, Following Single Ascending Oral Doses in Healthy Subjects - (11/08/10)
AASLD: Clinical Synergy of an Anti-HCV Nucleotide Analog with SOC: Viral Kinetics of PSI-7977 with SOC - (11/08/10)
AASLD: Phase II randomized, partially blind, parallel-group study of oral danoprevir (RG7227) with PegIFN alfa-2a (PEGASYS) plus ribavirin (COPEGUS) in treatment-naive genotype 1 patients with CHC: Results of planned Week 12 interim analysis of the ATLAS study - (11/21/10)
AASLD: HCV Late Breaker Posters this Morning at AASLD.....ABT450, BMS790052 NS5A+proteaseBMS650032, BI 201335+HCV polymerase inhibitor BI 207127+ribavirin - (11/02/10)
AASLD: Safety and Antiviral Activity of MK-5172, a Novel HCV NS3/4a Protease Inhibitor with Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients - (11/04/10)
AASLD: Efficacy and Safety of TMC435 in Combination With Peginterferon alfa-2a and Ribavirin in Treatment-naïve Genotype-1 HCV Patients: 24-Week Interim Results from the PILLAR Study - (11/02/10)
AASLD: Strong antiviral activity and safety of IFN-sparing treatment with the protease inhibitor BI 201335, the HCV polymerase inhibitor BI 207127, and ribavirin, in patients with chronic hepatitis C: the SOUND-C1 trial - (11/04/10)
AASLD: High rates of early viral response, promising safety profile and lack of resistance-related breakthrough in HCV GT 1/4 patients treated with RG7128 plus PegIFN alfa-2a (40KD)/RBV: Planned Week 12 interim analysis from the PROPEL study - (11/03/10)
AASLD: Dual, Triple, and Quadruple Combination Treatment with a Protease Inhibitor (GS-9256) and a Polymerase Inhibitor (GS-9190) alone and in Combination with Ribavirin (RBV) or PegIFN/RBV for up to 28 days in Treatment Naïve, Genotype 1 HCV Subjects - (11/04/10)
Pharmasset Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C - (10/28/10)
Pharmasset Announces Results of a 28-day Phase 2a Study with PSI-7977 for the Treatment of Chronic Hepatitis C Infection - (10/28/10)
AASLD: Safety and Pharmacokinetics of PPI-461, a Potent New HCV NS5A Inhibitor with Pan-Genotype Activity - (11/04/10)
AASLD: Telaprevir+pEg/RBV Based Combination Therapy in People with Hepatitis C, Regardless of Race or Stage of Liver Disease - 'up to 88% in African-Americans' Vertex press release - (11/01/10)
AASLD: No Impact of Insulin Resistance on Antiviral Efficacy of Telaprevir-based Regimen in HCV Genotype 1 Treatment-naïve Patients: Subanalysis of C208 Study - (11/21/10)
AASLD: Chronic Hepatitis C (HCV) Infections and the Risk of Depression and Other Adverse Events - (11/21/10)
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