Janssen R&D Ireland (Janssen), a partner of  Medivir AB, has published the primary efficacy and safety results from the global phase III study PROMISE. The results show that treatment with the protease inhibitor simeprevir (TMC435) resulted in sustained virologic response 12 weeks after cessation of treatment (SVR12) in 79 per cent of treatment-experienced adult patients with chronic hepatitis C genotype 1 and with compensated liver disease, including liver fibrosis in all stages.

Medivir AB is an emerging research-based specialty pharmaceutical company focused on infectious diseases.

Simeprevir administered once-a-day in combination with pegylated interferon and ribavirin. This study was achieved SVR12 in 37 percent of patients only treated with pegylated-interferon and ribavirin alone (placebo). Treatment failure or relapse occurred in three per cent and 19 per cent of patients in simeprevirarmen, compared to 27 per cent and 48 per cent of patients in the placebo arm. All patients had previously relapsed after treatment based on pegylated interferon.

Results were presented as a "late breaker" oral presentation at Digestive Disease Week 2013 in Orlando, USA.

“We are very pleased with the results of this phase III study in patients with relapsed. The results show a high cure rate of these treatment-experienced patients. This combined with the excellent safety profile and the fact that a large proportion of patients could complete all treatment in less time than current therapies should give new hope for large groups of patients with this disease,” says Charlotte Edenius, EVP Research & Development, Medivir AB.

In PROMISE, patients were randomized to receive simeprevir or placebo for 12 weeks in addition to pegylated interferon and ribavirin for 24 or 48 weeks. Results related to a secondary endpoint showed that 93 per cent of patients treated with simeprevir could reduce the duration of treatment with pegylated interferon and ribavirin for 24 weeks as a result of the criteria for response-guided therapy (RGT) was achieved. Among patients who had achieved RGT criteria to stop treatment at 24 weeks achieved SVR12 of 83 per cent.

Patients in the PROMISE stratified by HCV genotype / subtype 1 and IL28B genotype. In simeprevirarmen achieved SVR12 in 89 per cent (genotype CC), 78 per cent (genotype CT) and 65 per cent (genotype TT), compared to 53 per cent (genotype CC), 34 per cent (genotype CT) and 19 per cent (genotype TT) in the placebo arm.

Among patients with Metavir-gradation F0 to F2 was achieved SVR12 in 82 per cent of patients treated with simeprevir, compared to 41 per cent of patients treated with placebo. Among patients with Metavir-gradation F3 to F4 achieved SVR12 in 73 per cent and 74 per cent of patients treated with simeprevir, compared with 20 per cent and 26 per cent of patients treated with placebo. Metavir scale used to rate patients with liver disease in five stages after inflammation and fibrosis degree.

The most common adverse reactions in patients treated with simeprevir in PROMISE were fatigue (32 per cent versus 42 per cent for placebo), headache (32 per cent against 36 per cent for placebo) and flu-like syndrome (30 per cent versus 20 per cent for placebo). In simeprevirarmen was also observed rash (19 per cent vs. 14 per cent for placebo), pruritus (24 per cent versus 17 per cent for placebo), neutropenia (15 per cent versus 17 per cent for placebo), anaemia (11 per cent vs. 6 per cent for placebo), hyperbilirubinemia (6 per cent vs. 2 per cent for placebo) and photosensitivity (4 per cent versus no incidence for placebo). Treatment was discontinued due to adverse events for 1 patient in simeprevirarmen compared with no patients in the placebo arm.

PROMISE is a global, randomized, double-blind, placebo-controlled phase III clinical trial of the efficacy, safety and tolerability of simeprevir in addition to pegylated interferon and ribavirin are assessed and compared with only pegylated interferon and ribavirin in the treatment of adult patients with chronic hepatitis C genotype 1 and with compensated liver disease and who have relapsed after prior interferon-based treatment.

In PROMISE included 393 patients who were randomized to receive a 150 mg capsule simeprevir or placebo administered once-a-day in addition to pegylated interferon and ribavirin for 12 weeks, followed by the only pegylated interferon and ribavirin for 12 or 36 weeks (based on RGT-criteria). Patients in simeprevirarmen considered to have attained RGT criteria when their HCV RNA levels were Simeprevir.

Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB for the treatment of adult patients with chronic hepatitis C genotype 1 and with compensated liver disease, including liver fibrosis in all stages. Simeprevir acts by inhibiting hepatitis C virus protease which leads to the replication (replication) of the host cell is blocked. Registration applications were recently submitted to the authorities in Japan and the United States regarding simeprevir for the treatment of hepatitis C genotype 1 and an application for marketing authorization (MAA) has been submitted to the European Medicines Agency regarding simeprevir for the treatment of chronic hepatitis C genotype 1 or genotype 4.

The FDA has granted registration application "Priority Review". Janssen Pharmaceutical KK recently announced that the NDA filed in Japan regarding simeprevir for the treatment of chronic hepatitis C genotype 1. Global phase III studies of simeprevir in combination with pegylated intergferon and ribavirin include: · QUEST-1 and QUEST-2 in treatment-naïve patients, PROMISE in patients who have regained virus after prior interferon-based treatment ATTAIN in patients who have not responded to previous treatment (treatment-experienced) In parallel with these trials, phase III studies of simeprevir in treatment-naive and treatment-experienced HIV-HCV co-infected patients and HCV genotype 4 patients.

Simeprevir also studied in interferon-free phase II studies with direct-acting antiviral (Direct Acting Antiviral; DAA) combination therapies with and without the addition of ribavirin: Janssens non-nucleoside polymerase inhibitor, TMC647055 with low-dose ritonavir in treatment-naive patients Gilead Sciences nucleotide, sofosbuvir (GS7977) in treatment-naïve or patients who have failed prior treatment (null responders).