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BMS HCV Drug Development Program, Collaborations for IFN-free All Oral HCV Regimens: Daclatasvir+TMC435, Daclatasvir+VX-135
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In 2012 there was an agreement to study together Daclatasvir (BMS NS5A) in an IFN-free regimen in combination with TMC435, the Janssen HCV protease inhibitor, in treatment-naive & previous null-responder HCV genotype 1 patients. Daclatasvir is being studied in combination with Vertex's nucleotide/polymerase inhibitor VX-135.
"TMC435 and daclatasvir (BMS-790052)......http://www.natap.org/2012/HCV/041812_01.htm
.......In the agreement announced on 2ndDecember 2011, TMC435, a once daily potent NS3/4A protease inhibitor (PI) in phase III development for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection will be investigated in a combination in a phase II trial with Bristol-Myers Squibb's investigational NS5A replication complex inhibitor, daclatasvir (BMS-790052), also in phase III development.
In the upcoming phase II study the companies will evaluate the potential to achieve sustained viral response 12 and 24 weeks post treatment in null responder and interferon intolerant patients with HCV genotype 1. This study is planned to start later in 2012."
Vertex press release (July 2013): "Vertex and Bristol Myers Squibb Company (BMS) recently initiated dosing in New Zealand in a Phase 2 study of VX-135 in combination with daclatasvir, an NS5A replication complex inhibitor being developed by BMS. This first part of the study is evaluating 100 mg and 200 mg doses of VX-135 in combination with daclatasvir as part of 12-week treatment regimens in approximately 20 people with genotype 1 hepatitis C. Pending data from the initial cohort of patients, Vertex and BMS plan to expand the study to enroll additional patients with both genotypes 1 and 3. Safety and efficacy results from the first part of the study are expected to be available in early 2014."
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BMS HCV Drug Program
BMS has presented drug interaction data with Daclatasvir & HIV ARTs at CRO 2011, results immediately below. BMS has been in large phase 3 trials examining their 1st in class HCV NS5A Daclatasvir (BMS052), their HCV protease Asunaprevir (BMS650032) and reported phase 2 results at EASL in April 2013 for their triple oral combination IFN & Rbv free regimen that also includes their non-nuc BMS791325. Their new Peginterferon Peglambda is also currently in phase 3 studies, can be used in HCV & HBV. The combination of their Daclatasvir+GS7977 has been studied in phase 2 trials in genotypes 1/2/3 and the first to be studied in telaprevir/boceprevir failures with 100% SVR rates.
CROI: Assessment of HIV Antiretroviral Drug Interactions With the HCV NS5A Replication Complex Inhibitor Daclatasvir Demonstrates a PK Profile Which Supports Coadministration With Tenofovir, Efavirenz and Atazanavir/r - (03/9/11)
Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials) asunaprevir+BMS NS5A
Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials)
This study is currently recruiting participants.
Verified July 2012 by Bristol-Myers Squibb
First Received on April 5, 2012. Last Updated on July 26, 2012
Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)
Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)
EASL: NS5A BMS052 + nucleotide GS-7977 100% or 95% SVR for Patients Who Did Not Achieve SVR with Boceprevir/Telaprevir Triple Therapy, Resistance & Gt3 - (05/11/13)
EASL: Sustained Virologic Response With Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) in Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) or Boceprevir (BOC) - (04/27/13)
EASL: Interim Analysis of an Interferon (IFN)- and Ribavirin (RBV)-Free Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 in Treatment-Naive, Hepatitis C Virus Genotype 1-Infected Patients - (04/25/13)
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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, mean maximal 5.7 log reduction)
http://www.natap.org/2010/AASLD/AASLD_58.htm
Safety, Tolerability, Pharmacokinetics and Antiviral Activity following Single- and Multiple-Dose Administration of BMS- 650032 (Asunaprevir), a Novel HCV NS3 Inhibitor, in Subjects with Chronic Genotype 1 HCV Infection - (11/04/09)
A Phase 2a Study of BMS-791325, an NS5B Polymerase Inhibitor, With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Patients With Genotype 1 Chronic Hepatitis C Virus Infection
http://www.natap.org/2012/EASL/EASL_60.htm
EASL: Asunaprevir With Peginterferon-Alfa and Ribavirin in Treatment-Naive Patients With Genotype-1 or -4 Chronic Hepatitis C: SVR24 Results From a Randomized Phase 2b Study (AI447-016) - (04/27/13)
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Evaluation of Pharmacokinetic Drug-Drug Interaction (DDI) Between BMS-791325, an NS5B Non-Nucleoside Polymerase Inhibitor, Daclatasvir and Asunaprevir in Triple Combination in HCV Genotype 1-Infected Patients
http://www.natap.org/2013/EASL/EASL_11.htm
BMS052 HCV-NS5A Monotherapy in Phase 3 Now
http://www.natap.org/2012/HCV/082412_03.htm
Multiple ascending dose study of BMS-790052, an NS5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1
http://www.natap.org/2011/HCV/081611_02.htm
Safety and Pharmacokinetics of BMS-650032 Following Multiple Ascending Doses for 14 Days in Healthy Subjects
http://www.natap.org/2010/ICAAC/ICAAC_33.htm
EASL: Evaluation of Pharmacokinetic Drug-Drug Interaction (DDI) Between BMS-791325, an NS5B Non-Nucleoside Polymerase Inhibitor, Daclatasvir and Asunaprevir in Triple Combination in HCV Genotype 1-Infected Patients - (04/25/13)
EASL: DACLATASVIR COMBINED WITH PEGINTERFERON ALFA 2A ALFA-AND RIBAVIRIN FOR 12 OR 16 WEEKS IN PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 2 OR 3 INFECTION: COMMAND GT 2/3 STUDY - (04/27/13)
(Daclatasvir) BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients - (09/19/11)
EASL/2012: Potent Viral Suppression With the All-Oral Combination of Daclatasvir (NS5A Inhibitor) and GS-7977 (Nucleotide NS5B Inhibitor), +/- Ribavirin, in Treatment-Naive Patients With Chronic HCV GT1, 2, or 3 (100% SVR gt1, 91% gt2) - (04/19/12)
AASLD/2012: High Rate of Sustained Virologic Response With the All-Oral Combination of Daclatasvir (NS5A Inhibitor) Plus Sofosbuvir (Nucleotide NS5B Inhibitor), With or Without Ribavirin, in Treatment-Naive Patients Chronically Infected With HCV GT 1, 2, or 3 - (11/13/12)
EASL: Synergistic Interactions of HCV NS5A Replication Complex Inhibitors Sensitize Resistant Variants and Enhance the Efficacy of Daclatasvir (DCV, BMS-790052) In Vitro and In Vivo - (04/27/13)
Exposure-Response Analyses of Asunaprevir in Combination With Daclatasvir ± Peginterferon Alfa/Ribavirin Among Patients With Genotype 1 Chronic HCV Infection: Dose Selection for Phase 3 Clinical Trials
http://www.natap.org/2013/EASL/EASL_42.htm
High Rates of SVR Demonstrated in Phase II Study with Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS-791325 in Treatment-Naïve Patients with Genotype 1 Chronic Hepatitis C Infection - press release
http://www.natap.org/2013/EASL/EASL_01.htm
EASL 2012: Peginterferon Lambda-1A (Lambda) Compared With Peginterferon Alfa-2A (Alfa) in Treatment- Naive Patients With HCV Genotypes 2 or 3: First SVR24 Results From EMERGE Phase IIb - (04/20/12)
APASL 2012: PEGINTERFERON LAMBDA-1a(LAMBDA) SHOWS SUPERIOR VIRAL RESPONSE WITH IMPROVED SAFETY AND TOLERABILITY VERSUS PEGINTERFERON ALFA-2a(ALFA-2a) IN PATIENTS WITH CHRONIC HCV INFECTION (G1/2/3/4): EMERGE PHASE 2bTHROUGH WEEK 12RESULTS - (02/27/12)
APASL 2012: SAFETY AND EFFICACY OF PEGINTERFERON LAMBDA-1a (LAMBDA) COMPARED WITH PEGINTERFERON ALFA-2a (ALFA-2a) IN HCV-INFECTED PATIENTS (G1/2/3) WITH COMPENSATED CIRRHOSIS: EMERGE PHASE 2b EFFICACY AND SAFETY RESULTS THROUGH WEEK 12 - (02/27/12)
Peginterferon Lambda-1a (Lambda) is Associated With Less Autoimmune Thyroid Disease and Serious Autoimmune Disease Than Peginterferon Alfa-2a (Alfa) When Used in Combination With Ribavirin (RBV) for the Treatment of Chronic Hepatitis C Virus Infection - (06/14/13)
Clinical Pharmacology BMS HCV Program (EASL April 2013).......Bristol-Meyers Squibb R. Bertz Pres.
EASL: Evaluation of Pharmacokinetic Drug-Drug Interaction (DDI) Between BMS-791325, an NS5B Non-Nucleoside Polymerase Inhibitor, Daclatasvir and Asunaprevir in Triple Combination in HCV Genotype 1-Infected Patients - (04/25/13)
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AASLD: Dual Oral Combination Therapy with the NS5A Inhibitor Daclatasvir(DCV; BMS-790052) and the NS3 Protease Inhibitor Asunaprevir(ASV; BMS-650032) Achieved 90% Sustained Virologic Response (SVR12) in Japanese HCV Genotype 1b-Infected Null Responders - (11/08/11)
Dual therapy with the NS5A inhibitor BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected null responders - (01/13/12)
Quadruple Therapy With BMS-790052, BMS-650032 and Peg-IFN/RBV for 24 Weeks Results in 100% SVR12 in HCV Genotype 1 Null Responders: original slide presentation at EASL April 2011 Proof of Concept that SVR is Achievable Without Peg/RBV - 4/11 null responder patients achieved SVR w/o Peg/Rbv, with only BMS-790052 (NS5A inhibitor) + BMS-650032 (protease inh)
http://www.natap.org/2012/HCV/020312_02.htm
Evaluation of Drug Interaction Potential of the HCV Protease Inhibitor Asunaprevir (ASV; BMS-650032) at 200 mg Twice Daily (BID) in Metabolic Cocktail and P-glycoprotein (P-gp) Probe Studies in Healthy Volunteers
http://www.natap.org/2011/AASLD/AASLD_79.htm
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