Hepatitis C: Results from pivotal Phase 3 C-EDGE Programme and C-SURFER trial announced

MSD has announced the first presentation of data from the C-SURFER trial, the first to investigate an all-oral, once-daily, Ribavirin-Free Hepatitis C treatment regimen of grazoprevir (100mg) and elbasvir (50mg)* in treatment- naïve and treatment-experienced patients infected with chronic hepatitis C virus (HCV) genotype 1 and advanced chronic kidney disease (CKD), demonstrating SVR**12 rates of 99 percent.1 In addition, results from the C-EDGE clinical trial programme were announced, including data sets evaluating treatment-naïve, treatment-experienced and HIV co-infected patients with chronic hepatitis C virus genotypes 1, 4 or 6 Infection, demonstrating SVR 12 rates of 92 to 97 percent.^2,3,4 These data were presented at The International Liver Congress^TM 2015 - the 50th annual congress of the European Association for the Study of the Liver.

Dr Kosh Agarwal, Consultant Hepatologist and Transplant Physician at the Institute of Liver Studies, King's College Hospital, stated: "Data from the C-SURFER and C-EDGE trials are extremely encouraging given they provide well tolerated treatment options for 'more difficult to treat patient populations', such as cirrhotics. Specifically, those patients with co- morbidities, such as CKD, demonstrate high efficacy and favourable tolerability within a well conducted trial design".

The C-SURFER phase 2/3 clinical trial is evaluating patients infected with chronic HCV genotype 1 with advanced CKD stages 4 and 5† with or without liver cirrhosis, including treatment-naïve patients and patients who failed prior pegylated interferon HCV therapy. Following 12 weeks of immediate treatment with grazoprevir and elbasvir, in the modified full analysis set‡, 99 percent of patients receiving grazoprevir plus elbasvir achieved a sustained virologic response 12 weeks after completion of treatment (SVR12).¹

Dr Kosh Agarwal continued: "At present, there is limited treatment options for patients with advanced CKD including those on haemodialysis. The initial C-SURFER data demonstrates high cure rates without the need for ribavirin and interferon and favourable tolerability. This combination could improve patient care and access to renal transplantation".

Data sets from the ongoing C-EDGE Phase 3 clinical trial programme include treatment- naïve, treatment-experienced and HIV co-infected patients with chronic hepatitis C virus genotypes 1, 4 or 6 Infection. Patients in both the HCV infected treatment-naïve (C-EDGE TN) and HIV/HCV co-infected treatment-naïve (C-EDGE CO-INFXN) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95 percent.^2,3 In addition, HCV infected treatment-experienced patients (C-EDGE TE) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94 percent and 92 percent, respectively, and those treated for 16 weeks achieved SVR12 rates of 97 percent and 92 percent respectively.⁴

Further, patients with cirrhosis in C-EDGE TN and C-EDGE CO-INFXN trials treated for 12 weeks achieved SVR12 rates of 97 percent and 100 percent respectively.^2,3 In addition, HCV infected treatment-experienced patients (C-EDGE TE) with cirrhosis treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 89 percent respectively, and those treated for 16 weeks achieved SVR12 rates of 92 percent and 100 percent respectively.⁴

Dr Mark Toms, Medical Director, MSD UK, commented: "The data from the C-SURFER trial and C-EDGE programme show that we are progressing towards being able to achieve our ultimate goal: helping to eliminate hepatitis C. Having demonstrated consistently high rates of SVR12 in a diverse population of patients infected with chronic HCV, including the more difficult to treat patients with co-morbidities such as advanced chronic kidney disease, physicians could hopefully soon have another treatment option in their armamentarium. This is great news for the estimated 214,000 people in the UK⁵ living with hepatitis C, many of which remain undiagnosed".

About C-SURFER

C-SURFER is an ongoing Phase 2/3 clinical trial evaluating MSD's investigational grazoprevir plus elbasvir in patients infected with chronic HCV genotype 1 and with advanced chronic kidney disease (stages 4 and 5, including patients on haemodialysis) with or without liver cirrhosis.

Patients were randomized to one of two study arms:

• Immediate treatment group (ITG), grazoprevir plus elbasvir (blinded) once-daily for 12 weeks (n=111);
• Deferred treatment group (DTG), initially placebo (control arm) for 12 weeks followed by a 4 week follow up period and then with treatment with grazoprevir plus elbasvir (open label) once-daily for 12 weeks (n=113).

Of the 122 patients who received grazoprevir plus elbasvir, 83 percent were treatment-naïve, 36 percent had diabetes, 18 percent had stage 4 CKD, 82 percent had stage 5 CKD, 75 percent were receiving haemodialysis and 45 percent were African American. Among the those patients who received at least one dose of grazoprevir plus elbasvir, 5 percent (6/122) were excluded from the pre-specified primary efficacy analysis population, or modified full analysis set, due to missing data caused by death or early discontinuation for reasons unrelated to study drug.¹

The rates of serious AEs reported were 14 percent (16/111) in the ITG arms and 17 percent (19/113) in the placebo control DTG arm. The most common treatment-related AEs in the ITG arms and DTG arm (placebo) were headache (17%, 17%), nausea (15%, 16%) and fatigue (10%, 15%), respectively.¹

About the C-EDGE Program

C-EDGE is the Phase 3 clinical development program for MSD's investigational HCV treatment grazoprevir/elbasvir comprising five studies with more than 1,700 patients across more than 25 countries. These studies are evaluating grazoprevir/elbasvir in multiple genotypes (genotypes 1, 4 and 6) and diverse patient populations, including difficult-to-treat patients such as: treatment-experienced, patients with cirrhosis, HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and those receiving opiate substitution therapies. In the treatment naïve and co-infection study no serious adverse events were reported as drug related.

C-Edge TE 12 week arm:
Serious adverse events were reported in 4 patients in the grazoprevir/elbasvir only arm (4%) and 3 patients in the grazoprevir/elbasvir plus RBV arm (3%). The most common (greater than 10% incidence) adverse effects reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (19%, 27%), headache (21%, 20%) and nausea (9%, 14%).⁴

C-Edge TE 16 week arm:
Serious adverse events were reported in 3 patients in the grazoprevir/elbasvir only arm (3%) and 4 patients in the grazoprevir/elbasvir plus RBV arm (4%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (16%, 30%), headache (19%, 19%) and nausea (4%,17%).⁴