Hepatitis C - telaprevir
Current estimates indicate that about 130 million people around the world are infected with the hepatitis C virus, with three or four million more picking up the virus every year. Although about a fifth of people who are exposed to the virus manage to fight it off, the remainder become chronically infected.
Current estimates indicate that about 130 million people around the world are infected with the hepatitis C virus, with three or four million more picking up the virus every year. Although about a fifth of people who are exposed to the virus manage to fight it off, the remainder become chronically infected.
Untreated, up to half of these are likely to develop cirrhosis of the liver, and as many as 5% will develop liver cancer over the next two or three decades.
The virus can often be cleared with drug treatment, and the current therapy of choice involves a combination of pegylated interferon alfa and ribavirin. However, it is expensive and treatment needs to be continued for up to 48 weeks, and about half of those with chronic hepatitis C infection are not cured by this drug regimen. Side-effects are also a problem. A new drug that is under development by Vertex, telaprevir, is a protease inhibitor that interferes with the virus replication cycle.1 Because of the danger of resistance to the drug appearing, it is being developed for administration in combination with the current interferon and ribavirin combination.
A 4-week non-randomised, uncontrolled and open label Phase II trial was carried out of the drug in combination with pegylated interferon alfa-2a and ribavirin.2 Twelve treatment-naïve patients with hepatitis C were given the three drug combination, including 750mg of telaprevir every eight hours, for 28 days, and then switched to the standard therapy. At the end of the treatment period, viral RNA was undetectable, and after 12 weeks of the follow-on period, only one of the patients had detectable virus.
In a larger Phase II trial, which was randomised, double blind, placebo-controlled and parallel assignment, telaprevir was again given in combination with the standard therapy, to 250 treatment naïve patients.3 Four different treatment arms had different schedules, with three of the four receiving 750mg of the drug every eight hours for 12 weeks on top of standard therapy, followed by standard therapy alone for 0, 12 or 36 weeks afterwards. The fourth group received placebo plus standard therapy.
After the 12-week period, 88% and 79% of the telapravir groups had viral levels below 30 and below 10 iU/ml respectively, compared with 16% and 11% of the control group. Of those given telaprevir, 7% experienced viral breakthrough. Similar levels of adverse events were seen in all groups. Trials continue.