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New HCV Drugs - EASL & Beyond
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EASL: New Oral HCV Drugs at EASL - Report 4A
from jules: in this initial link immediately below & above "New Oral HCV Drugs at EASL - Report 4a", you will find a complete review of the oral & poster presentations of all the new data & studies presented at EASL for new orally administered HCV drugs & their study results. You will find brief & concise summaries of the data & study results for all the key presentations, and also links to the slide presentations & full poster data with graphs & tables. It is very helpful in trying to grasp & understand all the data by looking at the slides, graphs & tables. Over the next 6 months the FDA will be reviewing the first wave of new combinations, as several of them have been or will have been submitted to the FDA for review for approval. In the 1st half of 2014, the 2nd wave of new drugs & IFN-free combinations will have been submitted to the FDA.
There will be 3rd & 4th waves of new drugs and new IFN-free combinations over the next several years. The submissions to the FDA are called New Drug Applications, NDAs, submitted by the drug company developing the drug, the FDA reviews the data, may hold a public hearing & then notifies the public regarding approval, then shortly after that if approved they are in the pharmacy, simultaneously private & public insurers review the drugs & combinations so the patient can have their insurance approve that they will pay for the drug or combination.
Janssen submitted the NDA to the FDA for their new once daily protease inhibitor TMC435, to be used in combination with Peg/Rbv, at EASL results were reported for 2 of the phase 3 studies of this combination QUEST-1 and QUEST-2, inside the link "New Oral HCV Drugs at EASL - Report 7a" you can read brief summaries of the data & view the slides. Janssen is studying numerous oral-IFN-free combination regimens of their own & in collaboration with other companies. Of note, At CROI they reported results from a small phase 2 study, the COSMOS Study, which administered TMC435+GS7977 to null responders with or without RBV for 12 weeks & SVR8 was 96% with Rbv & 93% without Rbv.
CROI: SVR4 results of a once daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype 1 null responders - (03/06/13)
Gilead submitted the NDA to the FDA for the combination of the nucleotide GS7977+Rbv for patients with genotype 2/3 & for also for GS7977+Peg/Rbv for patients with genotypes 1, 4, 5 and 6. Gilead presented numerous studies at EASL, 8-9 key studies, all of them reviewed & reported in the link report immediately below. Of note, Gilead announced right after EASL initial results from a study of their IFN-free oral combination of GS7977+ their NS5A GS-5585 reporting 95-100% SVR rates & announced a larger phase 3 study of this combination starting, link in report below.
Gilead Reports Interim Data From Phase 2 LONESTAR Study - (05/03/13)
Gilead also reported 2 posters at EASL on their new pangenotypic 2nd generation NS5A GS5816 in preclinical study. Of note at CROI, the HIV conference in March Gilead reported results from a phase 2 study of GS7977+GS5885+Rbv in nulls & treatment naives showing 100% SVR12,
CROI: ELECTRON: 100% SVR Rate for Once-Daily Sofosbuvir Plus Ledipasvir Plus Ribavirin Given for 12 Weeks in Treatment-Naïve and Previously Treated Patients With HCV GT 1 - (03/04/13)
Boehringer Ingelheim will submit the NDA soon to the FDA for their new once daily HCV protease inhibitor called Faldaprevir & they presented at EASL results from their phase 3 study STARTVerso of Faldaprevir+pEg/Rbv, review & reports inside link. All these companies & many others are currently studying their new oral HCV drugs in IFN-free regimens containing 2-3 or 4 orally adminsitered drugs currently & will in time in be submitted in the 2nd, 3rd & 4th wave of NDA submissions to the FDA.
Of note, At CROI, Boehringer Ingelheim reported the first data in coinfected patients, since telaprevir & boceprevir, with their new once-daily HCV protease Faldaprevir + Peg/Rbv. They reported preliminary week 12 on-treatment results with 82% undetectable viral load, HCV-RNA. The reason this is noteworthy is because as they reported below the drug interactions of Faldaprevir with HIV ARTs ins very favorable so the combination can more easily be used with various HIV ART regimens than telaprevir, and they will soon be submitted their New Drug Application, NDA, to the FDA, and its expected this data will be submitted & they will request use of the regimen in coinfection.
CROI: STARTVerso 4: High rates of early virologic response in HCV genotype 1/HIV-co-infected patients treated with faldaprevir plus pegIFN and RBV - (03/04/13)
CROI: Pharmacokinetic interactions of darunavir/ritonavir, efavirenz, and tenofovir with the HCV protease inhibitor faldaprevir in healthy volunteers - (03/04/13)
CROI: Boerhinger Ingelheim Announes Interim Results Evaluating Virologic Response Rates in HCV/HIV Coinfected Patients Treated with HCV Protease BI201335, and Drug Drug Interaction Studies with HIV ARTs - (03/04/13)
BMS reported a number of studies at EASL including phase 2 results for their 3 oral drug IFN/Rbv-free regimen, they will soon start phase 3. Of note at EASL, I suggest you read this, BMS reported results from the 1st study to treat telaprevir & boceprevir failures with the 2 drug IFN-free regimen of 2 potent oral HCV drugs their NS5A inhibitor BMS052+ GS7977, with essentially 100% SVR rates with 24 weeks therapy:
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)
Abbvie (Formerly Abbott) reported data from phase 2 study of their 3 & 4 drug IFN-free oral regimens in treatment-naive & null responder non-cirrhotics, and reported 12 weeks therapy with the 4-drug regimen yielded 99% SVR12 & 96% SVR24, and in nulls 98% SVR12 & 95% SVR24, impressive results, see the link to "New Oral HCV Drugs at EASL - Report 4a". Phase 3 has been ongoing since the Fall 2012 and is looking at 12 weeks for null non-cirrhotics since the failures in the null responders group were breakthroughs on treatment.
Vertex is developing VX135, which is a nucleotide similar to GS-7977, which is being studied in numerous IFN-free combinations of new oral HCV drugs in collaborations with various companies with protease inhibitors or NS5A inhibitors, they reported 2 interesting posters at EASL, reviewed in report below. Merck reported phase 2 study results of their new 2nd generation once-daily protease inhibitor in combination with Peg/Rbv showing impressive 92% SVR rates, and they too are studying this protease MK5172 in combination with NS5A inhibitors in IFN-free regimens, including a study with BMS052 & a 2nd study with their own MK8742 a 2nd generation pangenotypic NS5A, which will be part of the 3rd & 4th waves of new combinations.
In Vitro Resistance Analysis of Merck's HCV NS5a Inhibitor MK-8742 Demonstrates Increased Potency AgainstClinical Resistance Variants and Improved Resistance Profile......http://www.natap.org/2012/EASL/EASL_46.htm
Roche started in the Spring 2012 a 3 & drug IFN-free regimen study, results expected to be presented soon.
3 & 4 Oral IFN-Free Roche HCV Regimens Studies, Treatment Naïve or Null Responders: setrobuvir+mericitabine+danoprevir/r+rbv. ANNAPURNA Study....... http://www.natap.org/2012/HCV/090412_01.htm
Achllion just announced starting a phase 2 study of a 2-drug oral regimen protease Sovaprevir+ 2nd generation NS5A ACH3102, links to results they reported at EASL below. Presidio is developing 2 pangenotypic oral HCV drugs, a non-nuc & a NS5A. Idenix is developing & studying in early studies a pangenotypic NS5A and has a program developing nucleotides that has been in preclinical & its expected later this year they will announce a clinical study with their 1st nucleotide. Both Idenix & Presidio are collaborating with other companies in combination oral IFN-free studies.
GILEAD SUBMITS NEW DRUG APPLICATION TO U.S. FDA FOR SOFOSBUVIR FOR THE TREATMENT OF HEPATITIS C - (04/08/13)
Medivir Press Release: New Drug Application has been filed with FDA for Simeprevir (TMC435) for combination treatment of adult patients with genotype 1 chronic hepatitis C - (04/03/13)
EASL: New Oral HCV Drugs at EASL - Report 4A
Achillion Initiates Phase 2 Interferon-Free Trial of Sovaprevir and ACH-3102 for Genotype 1 HCV, April 16, 2013
http://www.natap.org/2013/HCV/041613_04.htm
EASL: ACH-3102, A Second Generation NS5A Inhibitor, Demonstrates Potent Antiviral Activity in Patients with Genotype 1A HCV Infection Despite the Presence of Baseline NS5A-Resistant Variants - (05/09/13)
EASL: ACH-2684 Demonstrates Potent Viral Suppression in Genotype 1 Hepatitis C Patients With and Without Cirrhosis: Safety, Pharmacokinetic, and Viral Kinetic Analysis - (05/09/13)
EASL: ACH-2684: HCV NS3 PROTEASE INHIBITOR WITH POTENT ACTIVITY AGAINST MULTIPLE GENOTYPES AND KNOWN RESISTANT VARIANTS - (05/09/13)
EASL: No Clinically Significant Pharmacokinetic Interaction Between Sovaprevir and ACH-3102 in Healthy Volunteers - (05/09/13)
EASL: FINDINGS FROM CLINICAL VIROLOGY STUDIES ON ACH-3102 ARE CONSISTENT WITH PRECLINICAL OBSERVATIONS ON ITS IMPROVED POTENCY AGAINST GENOTYPE-1A HCV AND RESISTANT VARIANTS - (05/09/13)
EASL: Findings from Clinical Virology Studies on Sovaprevir, a Phase 2 HCV NS3 Protease Inhibitor, Indicate a High Pharmacological Barrier to Viral Resistance - (05/09/13)
EASL: Viral Kinetics Modeling to Predict cEVR and Aid in Dose Selection Decisions for Phase-2/3 Clinical Trials: ACH3102+ Sovaprevir, ACH2684 - (05/09/13)
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