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New DAA Phase 3 Studies for genotype 1 at EASL - in both Treatment-naives, treatment-experienced; simultaneous publications
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from Jules: Over 10,000 attended this EASL conference organizers reported, in London at the ExCel Center in the Canary Wharf section of London. I have been attending EASL every year since 1998 when the peginterferons were in development and NATAP.org has been providing HIV & hepatitis conference coverage since 1996, the advent of HIV protease inhibitors. This 2014 EASL ended Sunday March 13, all the new key study results for the new DAA IFN-free therapies in later stage development and the data has been reported by NATAP and can be viewed by clicking the link below, simultaneous publications included. Gilead & Abbvie reported Phase 3 data from large studies, with expected high SVR results, that will be submitted to the FDA & EMA european authorities to review for approval. Gilead reported three phase 3 studies for their fixed dose combination of sofosbuvir+ledipasvir: ION-1(naives 12 vs 24 weeks with & without RBV), ION-2 (treat-exp including a PI with & without Rbv for 12 & 24 weeks) and ION-3 (8 vs 12 weeks with & without Rbv) all of which I have reported through the NATAP listserve in real-time from the EASL meeting in London. Abbvie reported phase 3 studies TURQUOISE-II in patients with cirrhosis, SAPPHIRE-II in treatment-experienced patients, and SAPPHIRE-I in treatment-naive patients, all of which NATAP reported as well in real-time from London. SCROLL DOWN below To see LINKS to all the phase 3 studies, the slide presentations & simultaneous publications....
And of course several other studies have been reported here by both companies including in liver transplant patients and GT4, and 2 studies in HIV/HCV coinfected. Both the WHO & EASL presented their new HCV treatment guidelines at EASL, links to the guidelines at bottom of this report. Boerhinger Ingelheim announced in December 2013 they were canceling development of deleobuvir and at this EASL reported safety/efficacy for the 3-DAA combination with faldaprevir+PPI668+deleobuvir (http://www.natap.org/2014/EASL/EASL_36.htm).
Gilead reported results with Sofosbuvir+GS5816 (2nd generation NS5A) in Gt1-6 ( http://www.natap.org/2014/EASL/EASL_29.htm). Merck reported phase 2 C-WORTHY study results with MK5172+MK8742 +/- rbi in patients with cirrhosis & in previous null-responders where they looked at 12-18 weeks treatment
(http://www.natap.org/2014/EASL/EASL_21.htm), and Merck reported SVR4 results of 12 weeks of treatment in HIV coinfected patients (http://www.natap.org/2014/EASL/EASL_22.htm) and announced formerly here phase 3 has started. As well, the NIH group results with Sofosbuvir/Ledipasvir FDC in 50 coinfected mostly African-Americans Gt1, 22-38% with HAI fibrosis stage 3 with interim SRV4/SVR12 100% Rates (http://www.natap.org/2014/EASL/EASL_05.htm). BMS has previously started a number of phase 3 studies that are ongoing including three phase 3 studies of daclatasvir+sofosbuvir and phase 3 for their DAA therapy of daclatasvir+asunaprevir+BMS325, and at EASL reported large phase 3 study results for daclatasvir+asunaprevir in GTb ( http://www.natap.org/2014/EASL/EASL_45.htm) ( http://www.natap.org/2014/EASL/EASL_25.htm); globally outside USA Gt1b is a large segment of patients vs Gt1a which predominates in the USA . Janssen announced just before EASL the start of a large phase 3 study program for Simeprevir+Sofosbuvir (http://www.natap.org/2014/HCV/040314_01.htm), and at EASL reported updated results for Simeprevir+Sofosbuvir from COSMOS, cohorts 1 & 2, in null-responders, cirrhotics, and naives (COSMOS-1: http://www.natap.org/2014/EASL/EASL_46.htm) (COSMOS-2: http://www.natap.org/2014/EASL/EASL_26.htm). Janssen reported interesting simeprevir virology data, see links below.
Idenix reported data on for their nuke IDX21437, similar to sofosbuvir, which they are developing, now starting clinical studies in combination with their NS5A (http://www.natap.org/2014/EASL/EASL_58.htm), and they reported PK studies for their NS5A (IDX719), which is in several studies in combinations with IDX21437 and in collaboration with Janssen in 3-DAA combination with simeprevir & Janssen's non-nuc TMC647055 (http://www.natap.org/2014/EASL/EASL_53.htm), (http://www.natap.org/2014/EASL/EASL_52.htm).
Vertex reported SVR12 for their nuc VX135+daclatasvir (http://www.natap.org/2014/EASL/EASL_57.htm).
Achillion reported their latest data at APASL.
APASL: A Single Direct-acting Anti-viral Agent, ACH-3102, with Ribavirin is Able to Achieve a Robust Anti-viral Response in Subjects with Genotype 1b Chronic Hepatitis C Infection - (04/17/14)
APASL: ACH-3102 and Ribavirin in Genotype-1b Hepatitis C Patients: Confirmation of the High Barrier to Viral Breakthrough in Genotype-1b HCV - (04/17/14)
APASL: SVR4 Results for the Combination of ACH-3102 and Sovaprevir, With Ribavirin, in Patients With Genotype 1 Chronic Hepatitis C Infection - (04/17/14)
Later this year we can expect the FDA to approve the 2 new all-oral HCV regimens from both Gilead & Abbvie, where SVR rates go as high as 100% depending on the patient group (see the phase 3 study results), from the easiest to treat to the most difficult to treat who would be prior null responders with cirrhosis, and of course treatment in the setting of liver transplant, but look through the data and all the results are very encouraging. I have been working in HCV since 1998, reporting data, advocating with NYC, NYS, nationally and in Wash DC getting HCV into the Ryan White Care Act (click here for details), and this is the beginning of the new treatment era, we have been waiting for this for a long time.
EASL - The International Liver Congress 2014 49th Annual Meeting of the European
Association for the Study of the Liver
London, United Kingdom
April 9-13
EASL Presentations Phase 3 Studies GT1, treatment-naive & treatment-experienced:
EASL: All Oral Fixed-Dose Combination Ledipasvir/Sofosbuvir With Or Without Ribavirin for 12 or 24 Weeks in Treatment-Naive Genotype 1 HCV-Infected Patients: the Phase 3 ION-1 Study - (04/14/14)
EASL: All Oral Fixed-Dose Combination Ledipasvir/Sofosbuvir With or Without Ribavirin for 12 or 24 Weeks in Treatment-Experienced Genotype 1 HCV-Infected Patients: The Phase 3 ION-2 Study - (04/14/14)
EASL: Ledipasvir/Sofosbuvir With and Without Ribavirin for 8 Weeks Compared to Ledipasvir/Sofosbuvir for 12 Weeks in Treatment-Naļve Noncirrhotic Genotype-1 HCV-Infected Patients: The Phase 3 ION-3 Study - (04/11/14)
EASL: TURQUOISE-II: SVR12 RATE OF 92-96% IN 380 HEPATITIS C VIRUS GENOTYPE 1-INFECTED ADULTS WITH COMPENSATED CIRRHOSIS TREATED WITH ABT-450/r/ABT-267 AND ABT-333 PLUS RIBAVIRIN - (04/14/14)
EASL: SAPPHIRE-I: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/r/ABT-267, ABT-333, AND RIBAVIRIN IN 631 TREATMENT-NAļVE ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1 - (04/11/14)
EASL: SAPPHIRE-II: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/r/ABT-267, ABT-333, AND RIBAVIRIN IN 394 TREATMENT-EXPERIENCED ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1 - (04/10/14)
NEJM Publications:
ION-1 Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection - (04/14/14)
ION-2 Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection - (04/14/14)
ION-3 Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis - (04/11/14)
TURQUOISE-II ABT-450/r-Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis - Phase 3 TURQUOISE-II - (04/14/14)
SAPPHIRE-I Treatment of HCV with ABT-450/r-Ombitasvir and Dasabuvir with Ribavirin (in previously untreated patients with HCV genotype 1 infection and no cirrhosis) - (04/11/14)
SAPPHIRE-II Retreatment of HCV with ABT-450/r-Ombitasvir and Dasabuvir with Ribavirin - (04/10/14) NEJM
HIV/HCV Coinfected:
USE OF SOFOSBUVIR/LEDIPASVIR FIXED DOSE COMBINATION FOR TREATMENT OF HCV GENOTYPE-1 INFECTION IN PATIENTS COINFECTED WITH HIV (Interim results) - (04/10/14)
EFFICACY AND SAFETY OF THE ALL-ORAL REGIMEN, MK-5172/MK-8742 +/- RBV FOR 12 WEEKS IN GT1 HCV/HIV CO-INFECTED PATIENTS: THE C-WORTHY STUDY - (04/11/14)
COSMOS - Simeprevir+Sofosbuvir
EASL: Once-daily simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype-1 prior null responders with METAVIR F0-2: COSMOS study subgroup analysis - (04/14/14)
EASL: Simeprevir plus sofosbuvir with/without ribavirin in HCV genotype-1 prior null-responder / treatment-naļve patients (COSMOS study): primary endpoint (SVR12) results in patients with METAVIR F3-4 (Cohort 2) - (04/14/14)
Janssen Initiates Phase 3 OPTIMIST Trials of Once-Daily Simeprevir in Combination with Once-Daily Sofosbuvir for the Treatment of Genotype 1 Chronic Hepatitis C - (04/03/14)
Virology analyses of simeprevir in Phase 2b and 3 studies - (04/17/14)
Deep sequencing analyses of minority baseline polymorphisms and persistence of emerging mutations in HCV genotype 1-infected patients treated with simeprevir - (04/17/14)
GT4:
RESULTS FROM THE PHASE 2 PEARL-I STUDY: INTERFERON-FREE REGIMENS OF ABT-450/r + ABT-267 WITH OR WITHOUT RIBAVIRIN IN PATIENTS WITH HCV GENOTYPE 4 INFECTION - (04/16/14)
Sofosbuvir Plus Ribavirin, an Interferon-Free Regimen, in the Treatment of Treatment-Naļve and -Experienced Patients With Chronic Genotype 4 HCV Infection - (04/16/14)
Safety and Efficacy of Treatment With Interferon-Free, Ribavirin-Free Combination of Sofosbuvir + GS-5816 for 12 Weeks in Treatment-Naļve Patients With Genotypes 1-6 HCV Infection - (04/14/14)
GT1b:
PEARL-III: 12 Weeks of ABT-450/r/267 + ABT-333 Achieved SVR in >99% of 419 Treatment-naļve HCV Genotype 1b-Infected Adults With or Without Ribavirin - (04/16/14)
Efficacy and Safety of Daclatasvir in Combination With Asunaprevir in Cirrhotic and Non-Cirrhotic Patients With HCV Genotype 1b: Results of the HALLMARK-DUAL Study - (04/14/14)
All-Oral Dual Therapy With Daclatasvir and Asunaprevir in Patients With HCV Genotype 1b Infection: Phase 3 HALLMARK-DUAL Study Results - (04/14/14)
Safety and Efficacy of Treatment With Interferon-Free, Ribavirin-Free Combination of Sofosbuvir + GS-5816 for 12 Weeks in Treatment-Naļve Patients With Genotypes 1-6 HCV Infection - (04/14/14)
Post Liver Transplant
RESULTS OF THE PHASE 2 STUDY M12-999: INTERFERON-FREE REGIMEN OF ABT-450/r/ABT-267 + ABT-333 + RIBAVIRIN IN LIVER TRANSPLANT RECIPIENTS WITH RECURRENT HCV GENOTYPE 1 INFECTION - (04/14/14)
Sofosbuvir and Ribavirin for the Treatment of Recurrent Hepatitis C Infection After Liver Transplantation: Results of a Prospective, Multicenter Study - (04/16/14)
Sofosbuvir and Daclatasvir for Recurrent Hepatitis C After Liver Transplantation: Potent Antiviral Activity But Lack of Clinical Benefit if Treatment is Given Too Late - (04/16/14)
Merck
Efficacy and safety of MK-5172 and MK-8742 ± RIBAVIRIN IN Hepatitis C Genotype 1 Infected Patients with cirrhosis or previous null response: the C-WORTHY Study - (04/11/14)
EASL: SAFETY AND EFFICACY OF THE ALL-ORAL REGIMEN OF MK-5172 / MK-8742 ± RIBAVIRIN IN TREATMENT-NAIVE, NONCIRRHOTIC PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 1 INFECTION: THE C-WORTHy STUDY - (04/14/14)
EFFICACY AND SAFETY OF THE ALL-ORAL REGIMEN, MK-5172/MK-8742 +/- RBV FOR 12 WEEKS IN GT1 HCV/HIV CO-INFECTED PATIENTS: THE C-WORTHY STUDY - (04/11/14)
SVR AND SAFETY OF LOWER DOSES OF MK-5172 25 MG AND 50 MG DAILY FOR 12 WEEKS IN HCV GENOTYPE (G)1 TREATMENT-NAIVE NON-CIRRHOTIC PATIENTS - (04/11/14)
WHO, EASL Guidelines
WHO Guidelines for the screening, care and treatment of persons with hepatitis C infection - (04/09/14)
EASL Recommendations (Guidelines) on Treatment of Hepatitis C 2014 - (04/15/14)
AASLD Preparing Providers for Hepatitis Patients: Online Hepatitis Program for Primary Care Providers - (04/10/14)
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