Optimization of an Interferon-free Hepatitis C Virus Treatment Regimen Containing the NS3/4A Protease Inhibitor Faldaprevir, the Non-nucleoside NS5B Inhibitor BI207127, and Ribavirin for Genotype 1b-infected Patients

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

715. Optimization of an Interferon-free Hepatitis C Virus Treatment Regimen Containing the NS3/4A Protease Inhibitor Faldaprevir, the Non-nucleoside NS5B Inhibitor BI207127, and Ribavirin for Genotype 1b-infected Patients

Session: Poster Abstract Session: Antimicrobials: Novel Agents

Friday, October 4, 2013

Room: The Moscone Center: Poster Hall C

Posters 715_IFNFree_faldaprevir_deleobuvir.pdf (109.5 kB)

Background: SOUND-C1 demonstrated the potent antiviral activity of faldaprevir (FDV) and BI207127 + ribavirin (RBV) without interferon (IFN) in HCV GT1-infected patients. SOUND-C2 investigated the safety, efficacy, and treatment duration of FDV 120mg QD, BI207127 600mg BID or TID (with an additional induction dose of 1200mg at first intake) ± RBV for 16, 28, or 40 weeks in 362 HCV GT1-infected patients. Dose and treatment duration were optimized in SOUND-C3. Notably, recently completed pivotal phase 3 trials of FDV + PegIFN + RBV (STARTVerso™) have yielded promising results across both GT-1a and 1b patients, including patients with compensated cirrhosis.

Methods: Pharmacokinetic and pharmacodynamic analysis in SOUND-C2 indicated an interaction between FDV and BI207127 that increased plasma concentrations of each drug. Increased plasma concentrations of BI207127 correlated with gastrointestinal adverse events (AEs) and treatment discontinuation in the TID groups. SOUND-C3 eliminated the induction dose and limited treatment duration to 16 weeks in order to optimize therapy.

In SOUND-C3, GT1a patients (n=12) carrying the IL28b CC genotype (rs12979860, GT1a-CC) and GT1b patients (n=20) carrying any IL28b genotype were treated with FDV 120mg QD + BI207127 600mg BID without induction dose + RBV for only 16 weeks. Both studies included cirrhotic patients (9% in SOUND-C2 and 13% in SOUND-C3) and had a primary endpoint of SVR12.

Results: In SOUND-C2, SVR12 rates differed between GT1a- (up to 47%) and GT1b- (up to 85%) infected patients. The presence of cirrhosis had a minor influence on SVR12 rates. Nausea and vomiting were common AEs, especially in the TID arms, but were mainly mild.

In SOUND-C3, 95% (19/20) of GT1b-infected patients achieved SVR12 with the modified 16-week IFN-free regimen compared with 17% (2/12) of GT1a-CC-infected patients.

Conclusion: Modifying the IFN-free regimen of FDV, BI207127, + RBV in SOUND-C3 resulted in an SVR rate of 95% for GT1b-infected patients compared with 85% in SOUND-C2 after 16 weeks of treatment. GT1a-CC infected patients had a clearly lower SVR12 rate with 16-week therapy. The optimized 16-week IFN-free regimen is being investigated in phase 3 studies in GT1b-infected patients.

Parvez Mantry, MD, Hepatobiliary Tumor Program, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, Marcus Schuchmann, MD, Klinikum Der Johannes Gutenberg, University Hospital Mainz, Mainz, Germany, Ansgar Lohse, MD, Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Keikawus Arasteh, MD, EPIMED c/o Auguste-Viktoria-Klinikum, Berlin, Germany, Michael Manns, MD, Hannover Medical School, Hannover, Germany, Thomas Berg, MD, Department of Internal Medicine, University Hospital Leipzig, Leipzig, Germany, Stefan Mauss, MD, Zentrum für HIV und Hepatogastroenterologie, Düsseldorf, Germany, Michael Geissler, MD, Klinik Für Onkologie, Gastroenterologie Und Innere Medizin, Esslingen Hospital, Esslingen, Germany, Wulf Bocher, MD, Boehringer Ingelheim, Biberach, Germany and Stefan Zeuzem, MD, Gastroeneterology, Klinikum der Johann-Wolfgang-Goethe-Universität–Med. Klinik I, Frankfurt, Germany

Disclosures:

P. Mantry, Boehringer Ingelehiem: Investigator, Research grant

M. Schuchmann, Boehringer Ingelehiem: Consultant, Editorial Support and Speaker's Bureau, Consulting fee and Speaker honorarium
Norgine: Consultant, Consulting fee
BMS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Roche: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Merck: Speaker's Bureau, Speaker honorarium
Falk: Speaker's Bureau, Speaker honorarium
MSD: Speaker's Bureau, Speaker honorarium
DFG: Grant Investigator, Grant recipient

A. Lohse, Boehringer Ingelheim: Editorial Support, None

K. Arasteh, Boehringer Ingelehiem: Board Member, Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Grant recipient and Speaker honorarium

M. Manns, Roche: Consultant, Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Gilead: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Novartis: Grant Investigator, Grant recipient
Boehringer Ingelheim: Grant Investigator, Grant recipient
BMS: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Merck: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium
Janssen: Grant Investigator and Speaker's Bureau, Grant recipient and Speaker honorarium

T. Berg, BMS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Essex Pharma: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
GSK: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Novartis: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Roche: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Schering-Plough: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Vertex: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium

S. Mauss, Abbott: Grant Investigator, Scientific Advisor and Speaker's Bureau, Research grant, Research support and Speaker honorarium
BMS: Scientific Advisor and Speaker's Bureau, Speaker honorarium
Tibotec: Scientific Advisor and Speaker's Bureau, Speaker honorarium
Roche: Speaker's Bureau, Research support and Speaker honorarium
GSK: Scientific Advisor, Consulting fee
Gilead: Scientific Advisor, Consulting fee

M. Geissler, Boehringer Ingelehiem: Grant Investigator, Research grant

W. Bocher, Boehringer Ingelheim: Employee, Salary

S. Zeuzem, Abbott: Consultant, Consulting fee
Achillion: Consultant, Consulting fee
AstraZeneca: Consultant, Consulting fee
BMS: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Boehringer Ingelheim: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Gilead: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Janssen: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Merck: Consultant and Speaker's Bureau, Consulting fee and Speaker honorarium
Novartis: Consultant, Consulting fee
Roche: Consultant, Consulting fee and Speaker honorarium
Santaris: Consultant, Consulting fee

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