The National Institute of Health and Care Excellence (NICE) recently released the Appraisal Consultation Document (ACD) for the use of Olysio® (simeprevir), developed jointly by Janssen R&D Ireland and Medivir AB, for the treatment of chronic hepatitis C genotype 1 infection.
Janssen reports that it is satisfied with the preliminary decision by NICE, recommending the use of simeprevir for the treatment of chronic hepatitis C genotype 1 infection. Nevertheless, Janssen also noted that it is disappointed that NICE has not recommended simeprevir as a therapy for chronic hepatitis C genotype 4 infection, and for patients intolerant to interferon therapy.
“We are pleased that simeprevir has been recommended for the treatment of patients with genotype 1 hepatitis C when used in combination with peginterferon and ribavirin. However, we are disappointed with the preliminary recommendations from NICE for genotype 4 patients and those who are intolerant to interferon, and could therefore benefit from the use of a treatment regime that does not include it. We believe there is an unmet need in these patient groups that simeprevir can help address and that our submission to NICE demonstrates the cost-effectiveness of its use. However, we will attempt to address NICE’s concerns around this evidence, and hope its position will change,” commented Peter Barnes, Medical Director at Janssen.
Hepatitis C (HCV) is a disease of the liver caused by the hepatitis C virus, which is a blood-borne virus. This infection can induce liver damage, and patients that are chronically infected will probably develop liver pathologies, such as cirrhosis (destruction of normal liver tissue) and cancer. The most common routes of virus transmission are through unsafe injection practices; inadequate sterilization of medical equipment in some health-care settings; and untested blood and blood derivatives. Around 130–150 million people worldwide have chronic hepatitis C infection, normally referenced as a ‘silent killer,’ since it can be asymptomatic for many years. Approximately 350 to 500 thousand people die per year from hepatitis C-related liver diseases. Presently, there is no vaccine for hepatitis C, but antiviral therapies are successful in 50–90% of patients, although access to diagnosis and treatment is low — only 3% of people with hepatitis C receive treatment each year.
Simeprevir is an NS3/4A protease inhibitor (antiviral drug) that prevents viral replication by binding to the enzyme responsible for HCV replication thus inactivating it. This antiviral drug is indicated for the treatment of chronic hepatitis C infection in combination with peginterferon alfa-2a (pegIFN) and ribavirin (RBV), a drug that inhibits the virus of hepatitis C from replicating inside the cells, in genotype 1 and genotype 4 HCV-infected patients with compensated liver disease (a still functional diseased liver). The license for the treatment of simeprevir with pegIFN + RBV resulted from a clinical trial, with more than 1,000 patients, involving three crucial Phase 3 studies, QUEST-1, QUEST-24 and PROMISE5. In these 3 trials simeprevir was tested in combination with PegIFN/RBV in naïve patients and patients who have relapsed after prior interferon-based treatment. It was also shown that simeprevir, in combination with PegIFN/RBV, induced significant viral clearance levels when compared with PegIFN/RBV alone, thus demonstrating efficacy of simeprevir in patients with genotype 4 infection when used in combination with pegylated interferon and ribavirin. Importantly, for patients with chronic hepatitis C genotype 1 and 4 infections, which are intolerant to or not eligible for interferon (IFN) therapy, simeprevir was authorized as part of an all oral 12-week interferon-free Direct Acting Antiviral (DAA), agents that selectively target HCV, therapy with or without ribavirin (RBV), and simeprevir is normally well tolerated.
As a result of NICE not recommending the use of simeprevir with sofosbuvir (Gilead’s Sovaldi™), a drug with a potent antiviral activity against all identified HCV genotypes, patients with genotypes 1 or 4 hepatitis C not capable to take interferon-based therapy, will not have access to an effective and novel therapy. Meanwhile, these patients will risk developing a permanent liver damage such as cirrhosis or cancer and transmit hepatitis C to others.
Therefore Janssen will continue to work with NICE and other stakeholders to find a way to make simeprevir available for patients that cannot be treated with interferon-based therapy.