Vertex to meet hepatitis C patients' needs?

The results of a Phase II trial of Vertex' protease inhibitor, telaprevir (VX-950), showed the drug, in combination with Roche's pegylated interferon Pegasys (peginterferon alfa-2a; peg-IFN) and ribavirin (RBV) enabled some patients to clear the virus in 12 weeks. According to the World Health Organisation (WHO), the hepatitis C virus (HCV) is a major cause of acute hepatitis and chronic liver diseases such as cirrhosis and liver cancer. It is estimated that there are over 170m chronic sufferers worldwide, fuelling the HCV treatment market to over $2.3bn (€1.7bn) in 2004. The latest results from the trial, dubbed PROVE 1, were released at the Annual Meeting of the European Association for the Study of the Liver (EASL) last week and offer new hope to sufferers of genotype-1 HCV - the most difficult to treat and the most prevalent strain in the US, western Europe and Japan. While treatments for hepatitis B have met with considerable success, sufferers of HCV have not been so fortunate given the limited effectiveness of the two drugs available to them, peg-IFN and RBV. HCV has evolved over thousands of years to produce six genotypes and many subgroups, with genotypes 1 and 4 being not as responsive to interferon treatments that can take a year. This is twice as long as typical treatment times for genotypes 2 and 3. Genotypes 1, 2 and 3 are most commonly found in Europe and the US, whereas genotypes 4 and 5 are most prevalent in Africa. The company has previously stated its intentions to develop the drug as both a monotherapy and in combination with peg-IFN and RBV as in the current study which showed that the treatment was generally well tolerated and had a high rate of rapid viral response (RVR) and a low rate of on-treatment viral breakthrough. Many of the current treatment regimens fail and lead to relapse. The treatments are often not well tolerated with patients suffering from severe side effects. Vertex has also initiated a Phase IIb trial (PROVE 3) to study the effects of the drug on genotype-1 HCV patients who have not achieved a sustained viral response (SVR) with previous interferon-based treatments. If PROVE 3 is successful the treatment could offer hope to those patients that are unresponsive to peg-INF and RBV as there is currently a lack of alternative treatments with very few sufferers achieving a sustained viral load reduction upon retreatment. One major problem in stemming HCV transmission is that the virus can go undetected for up to 20 years after the initial infection. The US National Foundation for Infectious Diseases believes that complications from HCV are now the leading reason for liver transplants and account for nearly 2000 liver transplants a year. Any drug that can help cure the disease would reduce this number significantly. Competition ​ After a long dearth of potential drugs in companies' pipelines there is now a lot of activity in the area after recent technical advances in cell culture systems and replication assays have led to mechanistic discoveries of HCV infection allowing the discovery of various new potential antiviral targets. There are two HCV protease inhibitors that are competing with telaprevir to be the first on the market, namely Schering-Plough's SCH503034, which is also in Phase II, and Roche / Intermune's ITMN-191, which is in early clinical trials. Schering-Plough has stated they believe that SCH503034 has the potential to be a multibillion dollar drug. There are also three polymerase inhibitors currently in Phase II trials: Idenix/Novartis' valopicitabine (NM283), ViroPharma's HCV-796 and Roche's R1626. Roche/Idenix are also investigating valtorcitabine (val-LdC) - a first strand viral DNA synthesis inhibitor in Phase II HCV trials after initial success as an HBV treatment.