Clinical

REFILE: Telaprevir achieves virological response in refractory HCV-1 infection

Last Updated: 2010-04-13 18:32:01 -0400 (Reuters Health)

[Corrects a typographical error (changes "T24PR38" to "T24PR48") in last paragraph of story posted Apr 7, 2010 as 20100407clin012.]

NEW YORK (Reuters Health) - Patients with genotype 1 hepatitis C virus (HCV) who don't achieve a sustained viral response to peginterferon alfa and ribavirin will likely benefit from the HCV protease inhibitor telaprevir, an international randomized trial has shown.

In the April 8th New England Journal of Medicine, the researchers note that as many as half of patients with treatment-na�ve HCV infection will develop a sustained virologic response to the standard 24 or 28 weeks of treatment with peginterferon alfa plus oral ribavirin.

But when this treatment doesn't produce a sustained response, retreatment is unlikely to be successful, according to lead author Dr. John G. McHutchison of Duke University Medical Center in Durham, North Carolina, and colleagues.

For the PROVE3 study of telaprevir, Dr. McHutchison and colleagues at 53 sites enrolled 453 patients with HCV genotype 1 who had not achieved a sustained response to peginterferon alfa plus ribavirin. They randomly assigned patients to either:

-Telaprevir for 12 weeks and peginterferon/ribavirin for 24 weeks (T12PR24)

-Telaprevir for 24 weeks and peginterferon/ribavirin for 48 weeks (T24PR48)

-Telaprevir and peginterferon for 24 weeks (T24P24), or

-Peginterferon/ ribavirin only (controls).

Telaprevir was given as a 1125 mg loading dose, followed by 750 mg every 8 hours. The dose of peginterferon was 180 ug per week, and the ribavirin dosing was 1000 or 1200 mg/day, depending on body weight.

Twenty-four weeks after receiving the last drug dose, 51% of T12PR24 patients and 53% of the T24PR48 patients had undetectable viral loads, compared to 24% of the T24P24 group and 14% of the control group.

Rashes developed in 51% of patients receiving telaprevir, with 5% having severe rash. Fifteen percent of patients on telaprevir stopped taking the study drugs due to adverse events, compared to 4% of the control group, with rash being the most common reason for treatment discontinuation in patients taking telaprevir.

The patients who had cleared the virus after initial two-drug therapy and then relapsed were the most likely to respond to the triple therapy.

"The addition of telaprevir to current therapy as a re-treatment strategy in HCV-infected patients who had not had a sustained response to previous therapy significantly increased the likelihood of eradication of HCV infection," the researchers conclude.

They add that because adverse event discontinuation was less common in the T12PR24 group compared to the T24PR48 group, while treatment response rates were similar, "the T12PR24 regimen appeared to provide a better risk-benefit profile than the T24PR48 regimen."

The study was supported by Vertex Pharmaceuticals, the developer of telaprevir.

N Engl J Med 2010;362:1292-1303.