SciClone And Sigma-Tau Announce Positive Preliminary Results In Clinical Study Examining ZADAXIN'S Ability To Enhance Response To H1N1 Vaccine

Main Category: Swine Flu
Also Included In: Flu / Cold / SARS;  Immune System / Vaccines;  Infectious Diseases / Bacteria / Viruses
Article Date: 13 Jan 2010 - 0:00 PDT

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SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) and its partner Sigma-Tau S.p.A. have received initial topline results in a clinical study evaluating the potential of ZADAXIN® (thymalfasin) to enhance immune response to the MF59 adjuvanted H1N1 influenza monovalent vaccine, Focetria™ from Novartis. According to investigators, ZADAXIN treatment given with the H1N1 vaccine led to a highly statistically significant (p value < 0.01) increase in the percentage of subjects who seroconverted at 21 days after vaccination, when compared to those who received the H1N1 vaccine alone. Seroconversion is defined as a four fold or greater change in titers from baseline.

The randomized, three-arm open label study has a planned duration of 6 months and hence is still ongoing. It is being conducted in patients with end-stage renal disease who are on chronic dialysis. One cohort of patients received the H1N1 vaccine only, while the other two groups received either two 3.2 mg injections of thymalfasin (one seven days prior to vaccination and the second on the day of vaccination with Focetria), or two 6.4 mg injections of thymalfasin (one seven days prior to vaccination and the second on the day of vaccination with Focetria). Dosing regimens were based on preclinical results obtained in ferret and mouse models conducted in Europe and the U.S. earlier this year.

This ongoing study is designed to evaluate efficacy based on the proportion of patients achieving seroconversion -- a significant rise in specific antibody titers against H1N1 influenza. According to investigators, at 21 days following vaccination, 89% of patients in the low-dose ZADAXIN arm achieved seroconversion as did 88% of patients in the high-dose ZADAXIN arm, compared to only 56% of patients in the vaccine-only arm of the study. All patients are being followed for six months, to measure the durability of the protective titers, the second key parameter for the assessment of the immunogenicity of a vaccination. A higher seroconversion rate is indicative of the robustness of the immune response and may lead to more durable protection.

"We believe the rapid achievement of full enrollment in this study indicates the need for safe and effective vaccine enhancers to help protect immune compromised and elderly patients from H1N1 influenza," said Prof Trevor Jones, Group R&D Director, Sigma-Tau. "Given the complexities in treating those with compromised or weakened immune systems, we believe these are the patients most in need of protection from life-threatening virus infections such as H1N1."

"We are encouraged by the results of the study which, for the first time, used less frequent injections of ZADAXIN at the higher dose formulation," said Friedhelm Blobel, Ph.D., SciClone's President and Chief Executive Officer. "We hope that this pilot study will be completed successfully and that we can proceed thereafter with applications for regulatory approval regarding the use of ZADAXIN as an enhancer for vaccinations for H1N1 influenza using a one or two shot dosing regime. We have obtained regulatory approval for ZADAXIN for use as an adjuvant for regular influenza in more than 10 countries using multiple injections."

ZADAXIN has an excellent safety profile, with a long track record of patient use. Approximately 100,000 patients worldwide have used ZADAXIN in both clinical and commercial settings, alone and in combination with various antiviral and anticancer drugs.

About thymalfasin (ZADAXIN)

ZADAXIN, scientifically referred to as thymalfasin or thymosin alpha 1, is SciClone's synthetic preparation of thymalfasin, a peptide produced by the thymus gland which circulates in the blood naturally and is instrumental in immune responses. Published scientific and clinical studies have shown that thymalfasin helps stimulate and direct the body's immune system to improve response to vaccines, and to eradicate infectious diseases like HCV and HBV, as well as certain cancers.

Within the immune system, thymalfasin stimulates stem cell differentiation and increases production of antibodies and disease-fighting T cells, including CD4, CD8, and natural killer cells, while simultaneously slowing the breakdown and removal of these T cells. The increase in production of antibodies after thymalfasin treatment leads to an increase in response to vaccines, providing enhanced protection against infection; the increases in T-helper cells allows the immune system to tag and identify invasive agents and cancerous cells for removal.

In late 2008, SciClone and the FDA reached agreement in form of a Special Protocol Assessment on the design of a phase 3 registration trial for thymalfasin as a potential treatment for stage IV melanoma. Thymalfasin's potential beneficial role in treatment of melanoma derives from its demonstrated activation of the immune system through effects on Toll-like receptor 9 and signaling through increases in the nuclear factor NfKB, leading to increases in tumor-infiltrating lymphocytes, specific anti-tumor cytotoxic lymphocytes, and expression of MHC Class 1 and 2 cell-surface molecules. Evaluation of thymalfasin's utility in melanoma animal models has confirmed effective anti-tumor activity.

ZADAXIN is currently approved in more than 30 countries worldwide to treat a variety of indications. In clinical studies, more than 4,000 patients being treated with vaccines or infected with viral hepatitis B or hepatitis C, primary immunodeficiency diseases, or various cancers have been treated with ZADAXIN with virtually no drug-related side effects.

Source
SciClone
Sigma-Tau

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