Reuters Health Information (2010-08-09): Protease inhibitor improves treatment of hepatitis C
Drug & Device Development
Protease inhibitor improves treatment of hepatitis C
Last Updated: 2010-08-09 15:20:22 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Adding the hepatitis C virus (HCV) protease inhibitor boceprevir doubles the usual response rate to peginterferon and ribavirin, an international team reports.
The improvement over standard therapy is the largest ever reported, the lead author said in a statement.
Researchers at 67 sites in North America and Europe tested boceprevir (an oral NS3 protease inhibitor) in a randomized open-label phase II trial involving 520 treatment-naive patients with genotype 1 HCV infection.
They compared the standard 48-week protocol of peginterferon-alpha-2b plus ribavirin with various regimens that included the protease inhibitor.
In a paper released online today in The Lancet, lead author Dr. Paul Y Kwo of Indiana University School of Medicine, Indianapolis, and colleagues report higher rates of the primary endpoint -- sustained virological response (SVR) - in the various boceprevir groups.
Specifically, SVR rates were:
-- 38% for controls given peginterferon alfa-2b 1.5 mcg/kg plus ribavirin 800-1400 mg daily for 48 weeks;
-- 54% for those given peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 28 weeks (p = 0.013);
-- 56% among patients assigned to peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 24 weeks (p = 0.005);
-- 67% with peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 48 weeks (p < 0.0001);
-- 75% for patients assigned to peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 44 weeks (p < 0.0001).
"The 48-week treatment arm with 4 weeks of peginterferon lead-in and 44 weeks of peginterferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That's very impressive," Dr. Kwo said in a University press release.
He added in an email to Reuters Health, "It appears that response-guided therapy with use of the 4 week lead-in will be important in guiding treatment duration."
Anemia developed more often in boceprevir-based groups than the control group (55% vs 34%), as did dysgeusia (27% vs 9%).
Treatment was stopped for adverse events in 8% in the control group and in 9% to 14% in the boceprevir groups.
In a second part of the trial, the investigators tested a lower dose of ribavirin in the three-drug combination, but this led to a higher rate of viral breakthrough.
"Based on this phase II study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase III trials, from which preliminary results were recently released," said Dr. Kwo.
Merck, which is developing boceprevir, announced last week that the preliminary data from those later trials do support the drug's potency. However, anemia and other side effects caused more withdrawals in the invention groups than in the control group, and industry analysts believe these side effects might be an impediment to boceprevir's success. (See Reuters Health story of Aug 4, 2010.)
A rival protease inhibitor called telaprevir, which is being developed by Vertex Pharmaceuticals Inc., reportedly has similar outcomes with fewer side effects.
Funding for the current study came from Merck. The company says it expects to submit a New Drug Application with the Food and Drug Administration by year-end.