Antiviral Appears to Improve HCV Treatment

Antiviral Appears to Improve HCV Treatment
By Michael Smith, North American Correspondent, MedPage Today
Published: April 29, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit
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TORONTO, April 29 -- Adding an antiviral drug to standard hepatitis C therapy shortened the treatment time and increased response rates, two studies found.
Action Points

■Explain to interested patients that standard treatment for hepatitis C takes about 48 weeks and is associated with unpleasant side effects.


■Note that these studies suggest that adding an investigational antiviral drug to the mix shortens the treatment duration and increases the response time.
In the phase II studies, with slightly different designs, the investigational protease inhibitor telaprevir increased response rates by about 50%, the researchers reported in the April 30, 2009 issue of the New England Journal of Medicine.


The finding appears to be the first "material advance" in hepatitis C therapy since the introduction of pegylated interferon in 2001, according to Jay Hoofnagle, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md.


Commenting on the studies in an accompanying editorial, Dr. Hoofnagle said the drug -- which inhibits a specific serine protease of the hepatitis C virus -- marks the "beginning (of) a new era of treatment -- an era of antiviral agents developed specifically to target this virus."


In the first of the two studies -- both sponsored by the drug's developer -- John McHutchison, M.D., of Duke University, and colleagues randomized 250 patients with genotype 1 hepatitis C to one of four regimens.

The control group got standard therapy -- 48 weeks of ribavirin (Copegus, Rebetol) and peginterferon alfa-2a (Pegasys) -- and was compared with three other groups:

•79 patients who got telaprevir for 12 weeks and 24 weeks of the standard drugs
•79 patients who got 12 weeks of telaprevir and 48 weeks of standard therapy
•A small exploratory group of 17 patients who got telaprevir (1,250 milligrams on day one and 750 milligrams every eight hours thereafter) for 12 weeks, as well as peginterferon alfa-2a and ribavirin for the same 12 weeks

The primary outcome was sustained virologic response, defined as an undetectable level of hepatitis C RNA 24 weeks after the end of therapy.

The researchers reported that the sustained virologic response rate was 41% in the control group, compared with 61% in the patients who got 12 weeks of telaprevir and 24 weeks of the standard drugs, a difference that was significant at P=0.02.

The response rate was 67% in the patients who got 12 weeks of telaprevir and 48 weeks of the standard drugs, which was significant at P=0.002, compared with standard therapy.

In the exploratory group, which was not compared with the control group, the rate was 35%.

Standard treatment "cures less than half of patients and has significant side effects that make it very difficult for some patients to continue their treatment," Dr. McHutchison said in a statement.

"Our study found that by combining the standard therapy with the direct antiviral drug telaprevir, we could reduce the duration of treatment by 50%, to 24 weeks, and, at the same time, improve the cure rate by 50%."

One problem with telaprevir therapy was the incidence of adverse drug reactions -- primarily occurrence of rash -- which was higher than in the control group. This led to a higher rate of drug discontinuation than in the control group.

Results were similar in the second study, although the drug combinations analyzed were slightly different, according to Jean-Michel Pawlotsky, M.D., Ph.D., of the Henri Mondor Hospital in Paris, and colleagues.

The researchers compared outcomes in a control group of 82 patients who got standard therapy with outcomes among:

•81 patients who got telaprevir for 12 weeks and 24 weeks of the standard drugs
•82 patients who were treated with all three drugs for 12 weeks only
•78 patients who got telaprevir and peginterferon alfa-2a -- without ribavirin -- for 12 weeks

The rate of sustained virologic response for the control group was 46%, compared with 69% in the patients who got telaprevir and 24 weeks of peginterferon alfa-2a ribavirin. The difference was significant at P=0.004.

On the other hand, the rate in the other two telaprevir groups combined was not significantly different from that in the control group, the researchers found.

They concluded that ribavirin was a critical part of the treatment regimen.

The studies were supported by Vertex Pharmaceuticals.
Dr. McHutchison reported financial links with Vertex Pharmaceuticals, Schering-Plough, and Roche.

Dr. Pawlotsky reported financial links with Abbott, Astra-Zeneca, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Roche, Schering-Plough, Tibotec Pharmaceuticals, Valeant Pharmaceuticals, and Vertex Pharmaceuticals.

Dr. Hoofnagle reported no conflicts.

Primary source: New England Journal of Medicine
Source reference:
McHutchison JG, et al "Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection" N Engl J Med 2009; 360: 1827-38.

Additional source: New England Journal of Medicine
Source reference:
Hézode C, et al "Telaprevir and peginterferon with or without ribavirin for chronic HCV infection" N Engl J Med 2009; 360: 1839-50.

Additional source: New England Journal of Medicine
Source reference:
Hoofnagle, JH "A step forward in therapy for hepatitis C" N Engl J Med 2009; 360: 1899-1901