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ViroPharma and Wyeth Initiate Dosing in Phase 2 Study of HCV-796 in Treatment Naive Patients and Non-Responders
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EXTON, Pa., Oct. 24 /PRNewswire-FirstCall/ -- ViroPharma Incorporated (Nasdaq: VPHM) today announced that patient dosing has commenced in a Phase 2 study of HCV-796, a unique orally dosed hepatitis C viral polymerase inhibitor that interferes with the replication of hepatitis C virus (HCV). The Phase 2 study is being conducted with Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), ViroPharma's partner in development of HCV-796.
The objectives of this trial are to assess the safety, tolerability,
pharmacokinetic profile, and antiviral activity of HCV-796, when used in combination with pegylated interferon alfa-2b plus ribavirin compared to the current standard of care in treatment-naive subjects with HCV genotype 1 infection and in patients with HCV genotype 1 infection who were non-responders to prior HCV therapy. The companies will add an additional dose or doses of HCV-796 to the trial to further elucidate the dose response.
"Following the strength of the Phase 1 data, we have initiated a Phase 2 program to assess the efficacy of the compound as part of a triple therapy combination, and to continue to add to our safety database," commented Stephen Villano, M.D., ViroPharma's vice president of clinical research and development. "Hepatitis C is one of the most important unmet medical needs today. In the U.S., up to 70 percent of the estimated 3.2 million chronically infected persons will develop chronic liver disease, which is the single leading factor contributing to the need for a liver transplant in the U.S. each year. The current standard of care presents a problem for patients in terms of its cure rate and tolerability, and we believe that with continued clinical success HCV-796 could become part of
combination therapies that we hope will produce a much higher cure rate for patients in the future."
Phase 2 Design
The Phase 2 study is a randomized, open-label study of the safety, tolerability, antiviral activity, and pharmacokinetics of HCV-796 administered in combination with pegylated interferon plus ribavirin versus pegylated interferon plus ribavirin in HCV genotype 1-infected subjects who are naive to treatment. The combination of HCV-796, pegylated interferon and ribavirin will also be assessed in a group of HCV genotype 1 patients who have previously failed treatment (non-responders). Participation in all dose cohorts will include up to 48 weeks of treatment with combination therapy including HCV-796, and a 24-week follow-up period.
Initially, approximately 267 patients will be enrolled to target a minimum of 222 patients into 3 dosing groups: (1) 74 treatment naive patients receiving pegylated interferon and ribavirin (control therapy); (2) 74 treatment naive patients receiving pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours; and (3) 74 non-responders receiving pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours. After 12 weeks of dosing the 500 mg cohorts, tolerability and antiviral data will be reviewed to identify the additional dose group(s) to further
elucidate dose response. The subsequent dose cohort(s) will be enrolled in the same manner as the initial 500 mg cohort.
Outcomes assessed in the treatment groups will include:
-- Antiviral activity and percentage of subjects with undetectable plasma
HCV RNA levels at weeks 4, 12, 24, and 48;
-- Percentage of subjects with sustained virologic response (SVR), defined
as undetectable (less than 10 IU/mL, as measured by the Roche COBAS
TaqMan(R) assay) plasma HCV RNA levels at 24 weeks after the end of
treatment
Phase 1b Preliminary Combination Data
Preliminary data from a recently completed phase 1b study are available
through treatment day 14 from subjects in four combination treatment groups
(n= 9 -11 subjects per group) and on 15 subjects who received pegylated
interferon alone.
-- No dose-limiting toxicities were seen and although safety data remain
blinded, tolerability was consistent with that expected from pegylated
interferon.
-- Across all combination groups, the mean reduction from baseline in
plasma HCV RNA ranged from 2.1 to 2.7 log10 on day 7 and 3.3 to 3.5
log10 on day 14. This compared to a reduction of 1.1 log10 on day 7 and
1.7 log10 on day 14 with pegylated interferon alone. Consistent with
known effects of pegylated interferon, response varied by HCV genotype:
-- For genotype 1, mean reduction from baseline ranged from 1.5 to 2.3 log10 on day 7 and from 2.6 to 3.2 log10 on day 14 in the combination therapy groups compared to 0.9 log10 on day 7 and 1.3 log10 on day 14 for pegylated interferon alone.
-- Viral reduction greater or equal to 2 log10 at day 14 was achieved in
70 to 90 percent of subjects in all combination groups compared to 43
percent on pegylated interferon alone.
-- At day 14, 30 to 33 percent of patients in the combination groups
receiving greater than or equal to 250 mg BID of HCV-796 achieved viral
levels below the quantification limit of 50 IU/mL HCV RNA.
About Hepatitis C
Hepatitis C is a blood-borne virus recognized as a major cause of
chronic hepatitis worldwide. The World Health Organization estimates that
170 million persons worldwide are infected with HCV, and three to four
million persons are newly infected globally each year. According to the
U.S. Centers for Disease Control and Prevention (CDC), about four million
people in the U.S., or 1.8 percent of the population, are infected with
HCV.
Currently, there is no specific antiviral agent directed against HCV
that is commercially available, and no vaccine for prevention of HCV
infection. Several interferon products are available worldwide, but there
are substantial limitations to the use of these products when given as
monotherapy or in conjunction with ribavirin in the treatment of chronic
HCV infection. In addition to the relatively poor treatment response in
patients infected with genotype 1 HCV, the most common strain in the U.S,
Western Europe and Japan, the considerable side effects frequently
associated with the use of interferon can lead to discontinuation of
therapy in approximately 20 percent of patients.
About ViroPharma Incorporated
ViroPharma Incorporated is committed to the development and commercialization of products that address serious diseases treated by
physician specialists and in hospital settings. ViroPharma commercializes
Vancocin(R), approved for oral administration for treatment of antibiotic-associated pseudomembranous colitis caused by Clostridium
difficile and enterocolitis caused by Staphylococcus aureus, including
methicillin-resistant strains (for prescribing information, please download
the package insert at http://www.viropharma.com/docs/pulvules_pi.pdf).
ViroPharma currently focuses its drug development activities in viral
diseases including cytomegalovirus (CMV) and hepatitis C (HCV). For more
information on ViroPharma, visit the company's website at
http://www.viropharma.com.
About Wyeth
Wyeth is one of the world's largest research-driven pharmaceutical and
health care products companies. It is a leader in the discovery,
development, manufacturing, and marketing of pharmaceuticals, vaccines,
biotechnology products and nonprescription medicines that improve the
quality of life for people worldwide. The Company's major divisions include
Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal
Health.
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