New hepatitis C protease inhibitors achieve 80% ‘cure’ rate in patients with genotype 1 infection

A course of hepatitis C (HCV) combination therapy including the experimental HCV protease inhibitor telaprevir (VX-950) has produced a sustained viral response (SVR) in over 80% of treatment-naïve, hepatitis C-mono-infected patients with HCV genotype 1.

Another study found similar rates achieved by another protease inhibitor, boceprevir. The findings were annouced on Tuesday at the American Association for the Study of Liver Disease (AASLD) meeting in Boston, USA.

This response rate is at least 30% higher than the best SVR rates achieved in trials of patients with genotype 1 mono-infection treated with the standard pegylated interferon/ribavirin regimen.

Eighty-two per cent of patients achieved an SVR in 24 weeks (12 weeks on telaprevir plus interferon/ribavirin and 12 on interferon/ribavirin alone), when standard treatment for G1 lasts 48 weeks.

SVR, which is regarded as equivalent to a cure, is defined as the lack of detectable hepatitis C in the blood six months after the cessation of therapy.

The results were superior to results achieved in the previous PROVE studies of telaprevir - see this report - where SVR rates of nearly 70% were achieved compared with under 50% in patients taking placebo.

Final results from the present study, VX950-C208, were announced in a press release from the two companies developing the drug, Tibotec and Vertex, to accompany the conference presentation. This study had four differences from the PROVE study:

• There was no placebo-controlled arm: all patients took telaprevir;
• Half the patients took pegylated interferon-alfa-2a (Pegasys) and half took pegylated interferon-alfa-2b (PegIntron);
• Half the patients took 750mg of telaprevir three times daily, as in the PROVE studies, while half took 1250mg twice daily;
• If patients achieved an undetectable viral load by week four of the trial and maintained it till week 20, they were allowed to stop treatment at week 24. The 18% of patients who were exceptions to this carried on treatment till week 48.

Eighty-five per cent of patients taking telaprevir three times a day plus Pegasys achieved an SVR, and 82.5% of those on twice-a-day telaprevir.

In those taking PegIntron an SVR was achieved in 81% of those on thrice-daily telaprevir, and 82.1% twice-daily. These differences were not statistically significant. Interestingly, at week 12 there had appeared to be a difference in results, with 93% with undetectable HCV on thrice-daily telaprevir and 84% on twice-daily.

Regarding side-effects, the press release accompanying the trial results commented that “adverse events were similar to those observed in other trials with telaprevir.” The only figures given were for “serious adverse events leading to permanent discontinuation of all drugs,” which is a very restrictive definition. Three per cent discontinued the study due to rash by this criterion and 2% due to anaemia. In the PROVE 1 and 2 trials 21% and 12% of patients on telaprevir respectively discontinued therapy versus 11% and 7% on placebo. The main side effect of telaprevir is rash, with was classed as ‘severe’ in 7% and 15% of patients respectively in PROVE 1 and 2.

Final figures for viral breakthrough were not specified. Interim figures given in the abstract showed that nine patients (5.6%) had experienced an initial fall but then rebound of HCV by week 12 and that all nine had telaprevir resistance mutations.

The AASLD conference heard a lot of other news about new hepatitis C drugs. The results were also announced of PROVE 3, a trial of telaprevir in patients who have previously failed hepatitis C therapy. In this trial, nearly 40% of patients who previously failed to respond to pegylated interferon/ribavirin and nearly 70% who had responded but relapsed achieved an SVR with 24 weeks of treatment, while 76% of relapsers had an SVR with 48 weeks.

A study of Schering-Plough’s boceprevir, the first hepatitis C protease inhibitor to be trialled, found SVR rates of 82% in patients with genotype 1 who had an undetectable viral load by week four, and 79% by those who had not achieved one by week four but had by week 16. And a second boceprevir study found an SVR rate of 55% among patients who had previously failed to respond to pegylated interferon/ribavirin. In these studies, pegylated interferon/ribavirin is given for four weeks then boceprevir added for 24 weeks (in naïve patients) and 44 weeks (in previous non-responders).