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EASL NEW Oral HCV Drugs - Report 1 of 3
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Reported by Jules Levin
Original reported filed April 26 from EASL in real-time live. Yesterday Abbvie reported results from a phase 2b study of their oral IFN-free 4-drug regimen with 99% SVR rate with 12 weeks therapy in genotype 1 and 98% SVR with 24 weeks in null responders, see the table in this email of the results & click the link to read the entire slide presentation. Abbvie is in phase 3 with this regimen. In the Late Breaker poster session SVR12 results were reported from the QUEST-1 phase 3 study looking at the Janssen once-daily new protease TMC435+Peg/Rbv in treatment-naive patients, with phase 3 QUEST-2 being reported tomorrow at EASL, with an overal SVR12 rate of 80%, with 80% of patients achieving a RVR, rapid viral response (undetectable at week 4) & with 91% of these patients thus being able to shorten therapy to 24 weeks & achieve SVR. TMC435 is being studied in numerous IFN-free studies that contain 2 orals without IFN. Also in the same oral session Gilead reported results from phase 3 the Fusion & Fission studies which were published wednesday in the New England Jnl of Medicine & below are links to this publication & the pdfs with a breakout of the data & links to the slides presented yesterday, with 12 weeks therapy achieving a 98% SVR rate with GS7977+Rbv in genotype 2 non-cirrhotic patients & 91% in cirrhotic patients in the phase 3 FISSION Study. For genotype 3 61% of noncirrhotics & 34% of cirrhotics achieving SVR, so gt3 did not achieve good results, a different strategy will be studied for gt3 by Gilead & others. Then in the phase 3 FUSION Study 12 vs 16 weeks GS7977+Rbv was explored, with 96% SVR for gt2 noncirrhotics with 12 weeks therapy & 100% with 16 weeks. For gt2 cirrhotics 78% SVR was achieved with 16 weeks GS7977+Rbv therapy and 60% with 12 weeks. Again for GT3 SVR rates were less with 16 weeks performing much better than 12 weeks: 63% vs 37% in noncirrhotics & 61% vs 19% in cirrhotics. Again a better treatment strategy for GT3 will be examined by Gilead & others, but clearly gt2 patients achieved great results. Here are links to key data reported Thursday in the first HCV oral session on new HCV drugs. A poster Late Breaker was reported yesterday showing SVR results with the BMS 3-oral drug IFN/-Rbv free regimen including their protease Asunaprevir+the NS5A BMS052 (declatavir)+ their non-nuc polymerase inhibitor BMS325 showing high SVR rates of 94% perhaps higher because of lost to followup, see the data & link below. There are 2 additional Late Breaker posters from Thursday not are not reported here in my original reported I filed & distributed in real time at EASL as it was too late & I was too tired last night to write the reports but I did them & one is on the BMS protease BMS032 Asunaprenavir + PegRBv. This is a phase 2b study with patients receiving 200mg bid + Peg/Rbv for 24 weeks. The other was a poster from BMS on their development of a new "synergy" NS5A "molecule" that would be administered along with BMS052 & intended to prevent NS5A resistance. Both Janssen & Gilead have just recently submitted New Drug Applications to the FDA for indications for the use of GS7977 and for TMC435 with approvals expected by the end of the year. Other companies are completing phase 3 now & will be submitting NDAs to the FDA soon. Many additional studies are ongoing with these drugs in various types of IFN & Rbv free regimens with 2 or 3 oral HCV drugs., by all the companies, so as we move forward over the next few years the regimens will improve, will become more potent, efficient & effective. Gilead's coformulated combination of GS7977+ their NS5A GS5885 is in phase 3 now with an expected NDA application to the FDA in 2014. At CROI in April Janseen reported 96% SVR rates with the combination of TMC435+GS7977+Rbv for 12 weeks & 93% without Rbv in the COSMOS Study in null responders. BMS has reported 100% SVR rates with with their NS5A BMS052, now in phase 3, + GS7977 in treatment naives without Rbv & are reporting data here in telaprevir/boceprevir failures showing an expected 100% SVR rate. Of note, at EASL Gilead reported from the QUANTUM Study that patients who did not achieve an SVR with GS7977 were retreated & 76% achieved SVR.
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)
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)
EASL: SAFETY AND EFFICACY OF INTERFERON-FREE REGIMENS OF ABT-450/r, ABT-267, ABT-333 +/- RIBAVIRIN IN PATIENTS WITH CHRONIC HCV GT1 INFECTION: RESULTS FROM THE AVIATOR STUDY - (04/25/13)
EASL: Phase 3 Randomized Controlled Trial of All-Oral Treatment With Sofosbuvir + Ribavirin for 12 Weeks Compared to 24 Weeks of PEG + Ribavirin in Treatment-Naïve GT 2/3 HCV-Infected Patients (FISSION) - (04/25/13)
EASL: All Oral Therapy With Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment-Experienced Genotype 2/3 HCV-Infected Patients: Results of the Phase 3 FUSION Trial - (04/25/13)
ELECTRON, NEJM Jan 2013 Gane et al
Nucleotide Polymerase Inhibitor Sofosbuvir (GS-7977) plus Ribavirin for Hepatitis C - new published study
http://www.natap.org/2013/HCV/010413_04.htm
Sofosbuvir for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options - (04/24/13) New England Jnl of Medicine
Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial - (04/24/13)
EASL: 3-Oral BMS IFN/RBV-free Regimen- 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)
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: Simeprevir (TMC435) with peginterferon/ribavirin for chronic hCV genotype 1 infection in treatment-naïve patients: results from QUEST-1, a Phase III trial - (04/25/13)
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