Telaprevir Raises Response Rates in Hepatitis C

Telaprevir Raises Response Rates in Hepatitis C
By Michael Smith, North American Correspondent, MedPage Today
Published: April 07, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
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Action Points

* Explain to interested patients that this study shows that adding an investigational drug to standard therapy for hepatitis C during re-treatment improves the odds of getting rid of the virus.


* Caution that the drug in question -- telaprevir -- is not yet approved.

Re-treating hepatitis C patients with standard therapy plus the investigational protease inhibitor telaprevir significantly improved the chances of eradicating the virus, researchers said.

Up to 53% of patients with genotype 1 of hepatitis C, who had failed to respond to treatment initially or had relapsed, had a sustained response when telaprevir was combined with standard treatment, according to John McHutchison, MD, of Duke University, and colleagues.

In contrast, only 9% of patients re-treated only with standard therapy -- pegylated interferon alfa-2a and ribavirin (Rebetol) -- had a sustained response, McHutchison and colleagues reported in the April 8 issue of the New England Journal of Medicine.

The finding came from a complicated four-arm phase II trial that compared several combinations of the three drugs with a control arm consisting of just the standard therapy. Some of the data was reported at a scientific meeting late last year. (See AASLD: High SVR Rates Seen with Telaprevir for Hepatitis C)

Telaprevir, which targets the nonstructural 3/4A protease of the virus, is one of the most advanced of several such direct antiviral compounds now in the development pipeline.

For this study, the researchers treated 453 patients with the difficult-to-treat genotype 1 who had previously not had a sustained response to standard therapy. They were assigned to one of four arms:

* 114 to a control group -- dubbed PR48 -- who got standard therapy plus a placebo for 24 weeks followed by another 24 weeks of standard therapy
* 115 to the so-called T12PR24 group, which got telaprevir plus standard therapy for 12 weeks, followed by placebo and standard treatment for another 12 weeks
* 113 to the T24PR48 group, treated with 24 weeks of telaprevir plus standard therapy, followed by 24 weeks of standard therapy alone
* And 111 to the T24P24 group, treated with telaprevir and peginterferon alfa-2a for 24 weeks

Sustained response rates in all of the arms containing telaprevir were significantly better than those in the control arm, the researchers reported, although patients in the arm without ribavirin were less successful.

Specifically, the rates were 51% in the T12PR24 group, 53% in the T24PR48 group, and 24% in the T24P24 group, compared with 14% in the control group. The differences from control were significant at P<0.001, P<0.001, and P=0.02, respectively.

The lower response rate in the T24P24 group reinforces the need for ribavirin, McHutchison and colleagues said.

Response rates were higher among patients who had previously relapsed than among those who had never responded to standard therapy, the researchers said.

On the other hand, more patients in the telaprevir groups quit because of adverse events -- 15% compared with 4% in the control arm. Rash was one of the most common adverse events in the telaprevir groups, affecting 51% of patients, with severe cases in 5%.

However, discontinuation owing to adverse events was lower in the T12PR24 group than in the T24PR48 group -- 10% versus 26% -- while efficacy rates were comparable, the researchers noted.

The implication is that an "optimal treatment" may be a short period of telaprevir, followed by a longer period of peginterferon and ribavirin, they concluded.

The investigators cautioned about extrapolating these results to various ethnic groups as enrollment among those of African, Hispanic, and Asian descent was small.

The study was supported by Vertex Pharmaceuticals. McHutchison reported financial links with Vertex Pharmaceuticals, Schering-Plough, Roche, and Hoffmann-La Roche.

Several authors report being employees of Vertex.

Primary source: New England Journal of Medicine
Source reference:
McHutchison JG, et al "Telaprevir for previously treated chronic HVC infection" N Engl J Med 2010; 362: 1292-303.