Cap'n,
>>seems they still may be sitting on good news<<
You were right:
>>SAN MATEO, Calif., May 23 /PRNewswire/ -- SciClone Pharmaceuticals (Nasdaq: SCLN - news) announced that a new study published in the current issue of the peer-reviewed Journal of Viral Hepatitis adds further support to the critical biological role ZADAXIN® contributes to alpha interferon combination therapy used to treat chronic hepatitis C. The study results demonstrate that ZADAXIN increases the production of specific cytokines that fight viral infection while at the same time decreasing the production of other cytokines that make hepatitis C viral infection more impervious to immune response. The study was performed and authored by a group of Italian researchers led by Dr. Pietro Andreone of the University of Bologna.
The study was designed to compare the effects of ZADAXIN and alpha interferon, both separately and together, on cytokine (cell messenger) production in peripheral blood mononuclear cells taken from untreated chronic hepatitis C patients. T-lymphocytes in the body are classified as either Th1 or Th2 depending on the cytokines they produce. Th1 cells primarily produce interleukin-2 (IL-2) and gamma interferon, the cytokines involved in the immune-mediated eradication of the hepatitis C virus. Th2 cells primarily produce interleukin-4 (IL-4) and interleukin-10 (IL-10), which have been associated with the persistence of chronic hepatitis C infection. It has been suggested that when a swing toward Th2 cytokine production occurs it assists the hepatitis C virus to evade clearance by the body's immune system and thus become chronic.
Results ZADAXIN Produces Increase in Th1 and Correspondent Decrease in Th2
Incubation of cells with ZADAXIN alone resulted in a significant increase in Th1 cytokine production. In addition, ZADAXIN induced a decrease in the Th2 cytokines IL-4 and IL-10. By contrast, incubation with alpha interferon alone resulted in a smaller increase in Th1 cytokines (compared to ZADAXIN) and also an undesirable increase in Th2 cytokine production. Most importantly, the combination of ZADAXIN and alpha interferon resulted in an even greater Th1 increase than either drug alone, and reversed the interferon-based increase in Th2 production.
ZADAXIN treatment also resulted in an increase in 2'5'-oligoadenylate synthetase, a protein with direct antiviral activity.
Conclusion - Combination Therapy Required For Sustained Response
Other recent studies have shown that the clearance of the hepatitis C virus from the body following alpha interferon treatment is a two-phase process: first, the use of alpha interferon produces an initial dose-dependent decline of the viral load based on the prevention of viral replication or release; a second slower phase begins to occur while the viral replication is suppressed and this second phase relates to the clearance or elimination of hepatitis C virally-infected liver cells by the immune system. Although the first phase is seen in the majority of alpha interferon-treated patients, the second, and perhaps more important phase, is seen only in those patients that achieve a sustained response to therapy. A sustained response following hepatitis C therapy means that there is no detectable hepatitis C virus six months after the end of therapy, the time necessary to determine if the virus will return. The overall sustained response rate for alpha interferon monotherapy is around 10%.
An effective hepatitis C virus-specific immune response appears to be necessary for sustained clearance of the hepatitis C virus. The authors conclude that: ``combination treatment of hepatitis C with alpha interferon and ZADAXIN could be ideal, as it stimulates Th1 cell subsets without a concomitant stimulation of Th2. The association of ZADAXIN plus interferon is of interest also because it is very well tolerated and not associated with any significant side effects.''
Company Statement
``This study is extremely encouraging and validating for our recent U.S. phase 3 HCV trials combining ZADAXIN with alpha interferon,'' said Alfred R. Rudolph, MD, SciClone's Chief Operating Officer. ``Ribavirin has been combined with interferon as the current standard of therapy, and appeared to produce some reversal of increased Th2 production in culture, but it also has added toxicity to the side effect profile and it does not produce the same multi-faceted immune response to infected cells as ZADAXIN. Moreover, long-term response with the ribavirin plus interferon combination is about 28% in the most prevalent and difficult-to-treat variant of the hepatitis C virus (genotype 1). Our ZADAXIN phase 3 study targets the approximately 72% of this patient population that are non-responders to the current standard of care. There is no approved therapy for this group and any significant benefit can be enabling for the medical community.''
Background
The Centers for Disease Control estimate that up to 4 million people in the U.S. are infected with HCV. In its chronic progression, hepatitis C frequently leads to cirrhosis and liver cancer, both potentially fatal conditions. Hepatitis C has now emerged as the leading indication for liver transplantation. No optimal treatment yet exists for chronic hepatitis C. Alpha interferon historically has been the treatment of choice, and increasingly is combined with other therapeutic agents, particularly ribavirin. However, studies of the combination alpha interferon plus ribavirin show a negative response in up to 72% of patients infected with the highly prevalent and difficult-to-treat genotype 1 hepatitis C virus, i.e. they do not have a sustained response. Typically, genotype 1 infection is seen in 75% of the hepatitis C patients in the U.S. Meta-analyses of studies examining the re-treatment of non-responders (those patients that still have hepatitis C virus RNA after 12 months of alpha interferon plus ribavirin therapy) show that less than 8% of this patient group have sustained response after an additional course of therapy with alpha interferon or alpha interferon plus ribavirin. By contrast, in a pooled analysis of previous studies with non-responders, the combination of ZADAXIN plus standard alpha interferon demonstrated a 22% sustained response. Clinical data demonstrate that the combination of ZADAXIN plus interferon could represent a significant therapeutic advance in the global fight against hepatitis C.<<
snip
Sold my calls a half point too soon, it would appear. But ahead now, and perhaps this barrage of clinical news can keep it over 5 for a while.
Cheers, Tuck |
