Phase III Trial Shows Zadaxin Ineffective for Treatment of Hepatitis C among Nonresponders to Prior Treatment with Interferon

By Ronald Baker, PhD

Zadaxin (thymalfasin) is ineffective for the treatment of patients with chronic hepatitis C (CHC) who have failed previous interferon-based therapy, according to results of a Phase III clinical trial of Zadaxin used in combination with peginterferon alfa-2a (Pegasys).

In this trial, which enrolled 535 CHC patients, the combination of Zadaxin and peginterferon alfa did not result in a statistically significant improvement in sustained viral response (SVR) rates or in histological improvement compared to peginterferon alfa monotherapy.

Zadaxin appeared to be well tolerated and demonstrated no treatment-related adverse events or side effects. In addition, patients who received Zadaxin therapy were less likely to relapse after 48 weeks of treatment. Although a positive Zadaxin treatment-related trend was observed in SVR, it was not statistically significant.

SciClone Pharmaceuticals, the manufacturer of Zadaxin, is sponsoring a second, ongoing Phase III trial of the drug in Europe to assess its use in a triple combination regimen of Zadaxin plus peginterferon and ribavirin in nonresponders with early stage liver cirrhosis.

Following are excerpts from the announcement by SciClone concerning the Phase III trial results and the company’s plans for continued development of the drug as therapy for hepatitis C therapy and for melanoma:

"While all of us at SciClone are disappointed that this trial did not achieve statistical significance, there are several other important trials ongoing for Zadaxin including the ongoing triple therapy HCV clinical trial as well as a phase 2 malignant melanoma trial, both trials being conducted in Europe," said Ira D. Lawrence, M.D., President and Chief Executive Officer of SciClone Pharmaceuticals, Inc.”

"We will evaluate the data from our HCV trial in greater detail as well as the second Phase III trial results to determine and coordinate with Sigma-Tau, our European collaborator, the next steps regarding the development of Zadaxin in hepatitis C therapy. Importantly, we expect the ongoing European HCV clinical trial evaluating the triple therapy combination of Zadaxin, pegylated interferon alfa and ribavirin run by Sigma-Tau to provide further insight into Zadaxin's potential in augmenting the current standard of care for hepatitis C patients."

“SciClone expects that data from the second Phase III clinical trial using Zadaxin in combination with pegylated interferon alfa to treat non-responder HCV patients with early cirrhosis of the liver will be reported in May 2006, according to the announcement.”

About the US Hepatitis C Virus Phase III Trial

“HCV patients in the first of two Phase III clinical trials received a 48-week course of therapy of either Zadaxin (1.6 mg, twice a week) and pegylated interferon alfa (180 mcg, once a week) or placebo and pegylated interferon alfa followed by a 24-week observation period. The primary endpoints of each US HCV trial run by SciClone are the achievement of SVR and an improvement in the liver histological activity index assessed by liver biopsy at week 72.”

Although not statistically significant, 4% (10/269) of patients treated with Zadaxin plus pegylated interferon alfa achieved an SVR compared with only 2% (5/265) of patients treated with pegylated interferon alfa-2a (Pegasys) alone. No significant difference in histological improvement was observed between the patients treated with Zadaxin plus pegylated interferon alfa and those patients treated with pegylated interferon alfa alone.”

“All patients included in the trial had failed prior interferon-based treatment for hepatitis C virus, and had no cirrhosis of the liver. More than 75% of the patients enrolled in the trial were non-responders to the combination of interferon alfa (either regular or pegylated) and ribavirin, and were infected with the genotype 1 strain of the virus. Additionally, most patients in this trial had a high viral load, or greater than 850,000 copies per ml (or 5.93 log10) of the hepatitis C virus.

About the HCV Triple Therapy Trial

“SciClone's European partner Sigma-Tau is enrolling non-responder HCV patients in a 550-patient Phase III HCV triple therapy trial evaluating the triple combination of Zadaxin, pegylated interferon alfa and ribavirin.”

“This trial is different from the two U.S. Phase III hepatitis C trials in two important ways. First, patients in this trial will be treated with the anti-viral agent, ribavirin, in addition to Zadaxin and pegylated interferon alfa, whereas patients enrolled in the two U.S. Phase III trials were only treated with Zadaxin plus pegylated interferon alfa.”

“Second, patients enrolled in this trial are previous non-responders to the combination of pegylated interferon alfa plus ribavirin, whereas patients enrolled in the US Phase III trials were previous non-responders to any interferon-based therapy. SciClone and Sigma-Tau's objective for the European trial is to generate data on Zadaxin's use as part of a triple therapy combination for hepatitis C patients.”

About Zadaxin

“Zadaxin is a novel compound with immunomodulatory effects that facilitates the body's immune response to fight viruses and certain cancers. The compound is a synthetic version of the naturally occurring peptide thymosin alfa 1, generically referred to as thymalfasin. Zadaxin promotes T-cell maturation as well as increases the response of the immune system, with both functions playing an important role in eradicating virally infected and cancer cells. Zadaxin appears to be well tolerated, with few reports of significant side-effects or toxicities associated with its use.”

12/16/05

Source
SciClone Pharmaceuticals. SciClone Reports Results from First ZADAXIN Phase 3 Hepatitis C Trial. Press Release. December 14, 2005.

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