Clinical Trials

Date: 2015-04-08

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) taking place in Vienna from April 22-26

Company: Medivir (Sweden) Janssen Pharmaceuticals, a J&J company (USA - NJ) Idenix Pharmaceuticals (USA)

Product: simeprevir (TMC435) and sofosbuvir

Action mechanism:

direct-acting antiviral agent/protease inhibitor/RNA polymerase (NS5B) inhibitor

Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir.

Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication. This nucleotide NS5B polymerase inhibitor is developed by Gilead Sciences.

Disease:

chronic genotype 1 hepatitis C virus (HCV) infection

Therapeutic area: Infectious diseases

Country: Canada, USA

Trial details:

Latest news:

* On April 23, 2015, Medivir announced that its partner Janssen Sciences Ireland UC, publish positive results for simeprevir, the NS3/4A protease inhibitor for the treatment of hepatitis C virus (HCV) infection, at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) in Vienna. Late-breaking results from the phase III OPTIMIST-1 and OPTIMIST-2 trials highlight the clinical outcomes of simeprevir in an all-oral combination regimen in a wide range of patients with hepatitis C virus (HCV) infection. The results from the OPTIMIST-1 and OPTIMIST-2 trials are the first phase III data to be presented on simeprevir in combination with sofosbuvir (SMV/SOF) in patients with genotype 1 chronic HCV infection, both with and without cirrhosis. 

OPTIMIST-1 is a phase III, randomized, open-label trial to investigate the efficacy and safety of the all-oral regimen of SMV/SOF among treatment-naïve and treatment-experienced genotype 1 chronic HCV infected patients without cirrhosis. The primary objective was to show superior sustained virologic response (SVR) at 12 weeks after treatment (SVR12) with twelve and 8 weeks of treatment with SMV/SOF versus a historical control (patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon and ribavirin). 97% of patients treated with SMV/SOF for 12 weeks (n=150/155) achieved SVR12, which was superior to the SVR12 rate of  87% among the historical control.

- SVR12 rates of 100% were seen among patients with IL28B CC genotype (n=43/43) and those with baseline NS5A and NS3 Q80K polymorphisms (n=9/9). Patients treated with eight weeks of SMV/SOF achieved an SVR12 rate of 83% (n=128/155), which was not superior to the SVR12 rate of 83 percent in the historical control.

- High SVR12 rates were seen among patients with baseline HCV RNA IL28B CC genotype (93 %; n=38/41), patients with genotype 1b HCV infection (92 %; n=36/39), and patients without baseline NS5A and Q80K polymorphisms (89 %; n=78/88).

The most frequently reported adverse events in the 12-week and eight-week treatment arms were headache (14 and 17 percent, respectively), fatigue (12 and 15 percent, respectively) and nausea (15 and 9 percent, respectively).

OPTIMIST-2 is a phase III, open-label, single-arm trial to investigate the efficacy and safety of SMV/SOF in treatment-naïve and treatment-experienced genotype 1 chronic HCV infected patients with cirrhosis. The primary objective was to show superior SVR12 with twelve weeks of treatment with SMV/SOF versus a historical control. Twelve weeks of treatment with SMV/SOF resulted in SVR12 rates of 84 % (n=86/103), which was superior to the SVR12 rate of 70 % in the historical control. Higher SVR12 rates were seen in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100 %, n=13/13), patients with albumin ≥4 g/dL (94 %; n=47/50), and treatment-naïve patients (88 %; n=44/50). The most common adverse events were fatigue (20 percent), headache (20 percent) and nausea (11 percent).

* On April 8, 2015, Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), announced that clinical data for simeprevir, its NS3/4A protease inhibitor for the treatment of hepatitis C virus (HCV) infection, will be presented at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) taking place in Vienna from April 22-26. Several key presentations will report on the efficacy and tolerability of simeprevir in interferon-free combination regimens in Phase 2, Phase 3 and real-world clinical settings.

* On April 2, 2014, Medivir has announced that two phase III trials are recruiting patients to examine the efficacy and safety of the NS3/4A protease inhibitor simeprevir in combination with the nucleotide inhibitor sofosbuvir for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in treatment-naïve and treatment-experienced patients with and without cirrhosis. Ribavirin will not be administered in the OPTIMIST trials. The primary efficacy endpoint in each study is the proportion of patients achieving sustained virologic response 12 weeks after the end of treatment (SVR12).

Is general: Yes