Zadaxin shows promise in TTT

SciClone Pharmaceuticals, from San Mateo, CA, has reported that triple therapy of Zadaxin combined with pegylated interferon and ribavirin in a pilot trial in Mexico showed a sustained virologic response (SVR) in 19% of difficult to treat hepatitis C patients, non-responders infected with the genotype 1 strain of the virus.

'The response rate achieved by this genotype 1 subgroup is more than twice the 9% SVR observed in a separate, unrelated trial treating genotype 1 non-responder patients with pegylated interferon and a similar dose of ribavirin but without Zadaxin,' commented Dr Eduardo Martins, vice president, Medical Affairs of SciClone Pharmaceuticals, Inc. 'We are pleased by the results of this pilot study, particularly considering that a low dose of ribavirin was used and all of the patients are Hispanic, a patient population that is suggested to be less likely to respond to therapy. Although this was a small, uncontrolled pilot trial and reliable conclusions cannot be drawn from comparisons of results of different studies, we are encouraged by these results.'

Genotype 1 infected carriers account for 70% of the 2.7m chronic carriers of the hepatitis C virus (HCV) in the United States. Most genotype 1 patients fail initial therapy of pegylated interferon and ribavirin and become non-responders.

Non-responders to previous hepatitis C therapy are the subjects of SciClone's two U.S. Phase III clinical trials for Zadaxin in combination therapy with pegylated interferon. These trials are fully enrolled with over 1,000 patients and SciClone expects to report data in early 2006.

SciClone's European partner Sigma-Tau plans to begin enrolling non-responders in a 550-patient phase III triple therapy trial using the current standard dose of ribavirin, which is about 20% higher than the dose of ribavirin used in this pilot trial. SciClone's goal for the European trial is to generate data on Zadaxin's use as part of triple therapy for hepatitis C patients.

About the Triple Therapy Trial¶

The endpoint data from this pilot clinical trial were presented at the largest meeting of liver specialists in the world, the annual meeting of the American Association of the Study of Liver Disease (AASLD) held in Boston, MA. Table 1 summarises the response rates over the course of the trial: Using an intent-to-treat analysis, 16% (4/25) of all patients and 19% (4/21) of the difficult to treat genotype 1 patients achieved an SVR at the trial endpoint (72 weeks). Using a per protocol analysis which excludes the 2 patients who dropped therapy by week 24 due to adverse side effects from pegylated interferon, 17% (4/23) of all patients and 21% (4/19) of genotype 1 patients achieved an SVR. None of the other four patients, all genotype 2, achieved an SVR.

This small, open label, single-arm pilot trial enrolled 25 Hispanic patients infected with HCV, none of whom had responded to previous treatment of at least 24 weeks of interferon plus ribavirin. Patients received 48 weeks of therapy of a standard dose of Zadaxin (1.6 mg/twice-weekly), a standard dose of pegylated interferon alfa-2a (180 mcg/week), and a low dose of weight-based ribavirin (800-1,000 mg/day). At the end of 48 weeks of therapy, patients were observed for 24 weeks to determine SVR at week 72, the trial endpoint. During the course of therapy, 44% (11/25) of patients required a dose reduction of pegylated interferon, 28% (7/25) required a dose reduction of ribavirin and none required a dose reduction of Zadaxin. As in all previous Zadaxin studies, the safety profile was excellent without significant Zadaxin related side effects or toxicities.

Background on Hepatitis C Trials

Sigma-Tau, SciClone's European partner, plans a 550-patient, multi-centre, double-blinded, placebo-controlled phase III clinical trial to determine the potential additive benefit of Zadaxin to the standard hepatitis C treatment regimen of pegylated interferon and ribavirin in non-responders. Patients will receive 48 weeks of treatment with either Zadaxin (1.6 mg/twice-weekly) or placebo in addition to a standard dose of pegylated interferon alfa-2a (180 mcg/week) and the current standard dose of ribavirin (1,000-1,200 mg/day). Following treatment, all patients will be followed for an additional 24 weeks to determine SVR. SciClone's ongoing US phase III clinical trials are fully enrolled with over 1,000 patients and are multi-centre, randomised, double-blinded studies. Patients are receiving 48 weeks of treatment with either Zadaxin (1.6 mg/twice-weekly) or placebo in combination with pegylated interferon alfa-2a (180 mcg/week). Following treatment, all patients will be followed for an additional 24 weeks to determine SVR. The company expects to report results from these trials in early 2006.