SciClone Pharmaceuticals Says Hepatitis C Drug Trial's Interim Data Promising
FOSTER CITY, CA -- Feb 11, 2008 -- SciClone Pharmaceuticals and Sigma-Tau S.p.A today reported promising blinded interim data from a large, randomized phase 3 clinical trial evaluating ZADAXINÂ® (thymalfasin) in combination with pegylated interferon alpha and ribavirin as a treatment for patients with hepatitis C virus (HCV) who have not responded to prior therapy with pegylated interferon alpha and ribavirin. Full unblinded data from the trial will be available in the third quarter of 2008.
48 Week End of Treatment Response
The interim blinded HCV data show that at the end of 48 weeks of therapy, 171 out of 553 total patients, including both treatment and control group patients, responded to treatment. A response to treatment is defined as having no detectable HCV RNA circulating in the blood at the end of 48 weeks of therapy.
72 Week Sustained Virologic Response
Of the 171 patients who responded after 48 weeks of therapy, 150 patients have completed the 24-week follow up period (72 week observation) and 54 patients have achieved a sustained virologic response (SVR). Of the remaining 21 patients who responded at the end of therapy, 12 were HCV negative at week 60 (12-week follow-up observation period), and two had yet to reach the week 60 follow-up point. All patients will complete the observation period by the end of the second quarter 2008. While these data include both treatment and control group patients, SciClone and Sigma-Tau believe the trend is promising in light of other recent clinical trial results in non-responder HCV patients retreated with only pegylated interferon alpha and ribavirin which demonstrated SVR rates of 3 to 8% at the 72 week observation point. If the final results of this trial are positive, SciClone and Sigma-Tau plan to meet with the regulatory authorities in the United States and Europe to determine the most expeditious process to bring this therapy to the market.
"These interim HCV data are promising because, although we do not know the breakdown between thymalfasin treated and control group patients who have achieved an SVR, this is already a strong overall response for nonresponder patients. We look forward to reporting full data from this trial in the third quarter of 2008," said Mario Rizzetto, M.D., Professor of Gastroenterology, San Giovanni Battista Hospital, University of Torino, Italy, and lead investigator of the trial. "Thymalfasin's mechanism of action as an immune stimulator may prove to be ideal in the treatment of chronic hepatitis C, where the immune system is suppressed and cannot effectively fight the disease on its own."
"We believe that thymalfasin could represent an important advance in the treatment of hepatitis C patients and address a growing and acute unmet need. We estimate that nearly 1 million HCV patients in the United States alone have failed or will fail currently approved therapy, particularly those who have not responded to prior therapy," stated Friedhelm Blobel, Ph.D., President and Chief Executive Officer of SciClone Pharmaceuticals, Inc. "The treatment approach for HCV using a combination of thymalfasin together with pegylated interferon plus ribavirin is patent protected by SciClone in most major markets including the United States and Europe until 2021."
Thymalfasin Phase 3 Programs
"The information from these interim data is important in determining the optimal phase 3 development pathway for thymalfasin," noted Dr. Blobel. "In light of the promising interim data, we and Sigma-Tau are analyzing the many factors relative to our thymalfasin HCV and malignant melanoma programs."
In June 2007, SciClone reported positive phase 2 clinical trial results from Sigma-Tau's 488 patient study demonstrating thymalfasin met its primary endpoint in tumor response and, more importantly shows promise in extending survival for patients diagnosed with stage IV malignant melanoma. The companies are planning the design of a phase 3 melanoma trial and their regulatory strategy including a Special Protocol Assessment (SPA) to be filed with the Food and Drug Administration. Thymalfasin phase 3 clinical development and commercialization plans for HCV and melanoma have potentially significantly different timelines, costs, sizes of prospective addressable markets, competitive products and other factors. Consequently, before proceeding further with the melanoma trial, SciClone and Sigma-Tau will review the final 72 week results for the current HCV clinical trial in the third quarter of 2008 in order to determine the next steps for an optimal thymalfasin development program for the HCV and malignant melanoma indications.
Today, Israel Rios, M.D., Chief Medical Officer of SciClone Pharmaceuticals, will participate in a panel discussion on "HCV: Beyond Coin Toss SVRs" at the BIO CEO and Investor Conference 2008 in New York City. Dr. Blobel will present a corporate overview at the conference tomorrow, February 12, 2008, at 4:15 p.m. ET. To access the live audio webcast of the corporate presentation, log on through a link located in the Investor Relations section of SciClone's website at www.sciclone.com. A replay of the webcast will be available until March 14, 2008.
Thymalfasin Triple Therapy for HCV
The ongoing phase 3, multi-center, double-blinded, randomized study enrolled 553 predominately genotype 1 HCV patients who have not responded to previous treatment with pegylated interferon alpha and ribavirin. Patients were randomized, in a one-to-one ratio, to receive either thymalfasin or a placebo, and all patients received pegylated interferon alpha and ribavirin. After completing 48 weeks of treatment, patients are monitored twice during a 24-week observation period at week 60 and week 72.
The primary endpoint of the trial is sustained virological response (SVR), defined as the absence of HCV RNA measured at week 72, which is the end of the 24-week observation period. The secondary endpoints are normalization of ALT (an enzyme that when present in increased levels is an indicator of inflammation or damage of the liver) measured at the end of weeks 48 and 72, absence of HCV RNA measured at week 48, and an improvement in liver biopsy. Details of the study design and preliminary blinded safety data were reported by Professor Rizzetto at the 'Thymosins in Health and Disease First International Symposium' held last year in Washington, D.C. and also were published in September 2007 in a special edition of the Annals of the New York Academy of Sciences.
The design of this phase 3 clinical trial is derived from the positive results from a 2005 pilot study conducted by a team led by Jorge L. Poo, M.D., Chief Scientific Officer of CIF-Biotech at the Medica Sur hospital in Mexico City. This study evaluated the use of thymalfasin in combination with pegylated interferon alpha 2a and ribavirin to treat 40 patients who had not responded to prior therapy with the non-pegylated form of interferon and ribavirin. Measured on an intent-to-treat basis, this small study demonstrated a 22% SVR for the most difficult to treat genotype 1 patients.
Triple therapy, the addition of another agent to the combination of pegylated interferon alpha and ribavirin, is now an accepted approach in efforts to develop a new therapeutic regimen that may provide HCV patients with a potentially better chance to reach a sustained virological response. SciClone was a pioneer in developing the triple therapy approach, and today several drug developers are combining their drug in a triple therapy regimen for HCV clinical trials, typically after discovering that their drug alone or in combination with only pegylated interferon alpha did not provide satisfactory results in comparison to the standard therapy of pegylated interferon and ribavirin. In 2005 and 2006, SciClone completed two phase 3 clinical trials using thymalfasin in combination with pegylated interferon without ribavirin. Although those trials did not show statistical significance in the thymalfasin treatment arm, a positive thymalfasin-related trend was observed in SVR.
About Hepatitis C Virus
HCV is a blood-borne viral disease which causes inflammation of the liver. The World Health Organization estimates that 170 million people worldwide are infected with HCV, and the Centers for Disease Control estimates that approximately 8 to 10 million people are infected with HCV throughout the U.S. and Europe. Of these patients, approximately 85% are chronically infected, and the persistent liver inflammation in chronically infected patients can develop serious complications including cirrhosis of the liver, liver failure and hepatocellular carcinoma or liver cancer. Only about half of all naÃ¯ve patients treated with current therapy achieve an SVR, and SciClone estimates nearly 1 million HCV patients in the United States alone have failed or will fail current therapy. The markets for HCV therapeutics in the three major economic regions of the United States, Europe and Japan are estimated to total approximately $3 billion currently and are expected to grow to approximately $10.6 billion by 2014.
ZADAXIN, scientifically referred to as thymalfasin or thymosin alpha 1, is SciClone's synthetic preparation of thymalfasin, a thymic peptide which circulates in the blood naturally, and is instrumental in the immune response to certain cancers and viral infections. Published scientific and clinical studies have shown that thymalfasin helps stimulate and direct the body's immune response to eradicate infectious diseases like HCV and HBV, as well as certain cancers. Thymalfasin appears to be well tolerated with few reports of significant side effects or toxicities associated with its use.
Thymalfasin elicits a variety of immune system responses against viruses. One such response is an increase in production of certain subsets of white blood cells and their differentiation into CD-4 helper-cells, specifically towards differentiation into the Th1 subset of CD-4 helper cells (Th1 cells secrete cytokines such as interleukin-2 (IL-2) and gamma interferon that can help the immune response). Moreover, as thymalfasin increases differentiation into Th1 cells, it also results in decreased CD-4 cell differentiation into the Th2 subset of CD-4 helper cells that produce cytokines, such as IL-4, which are associated with persistence of viral infection. In addition, thymalfasin stimulates several other components of the immune response that help the body attack and kill virally-infected cells.
SciClone Pharmaceuticals is a biopharmaceutical company engaged in the development of therapeutics to treat life-threatening diseases. SciClone's lead product ZADAXINÂ® is currently being evaluated in late-stage clinical trials for the treatment of hepatitis C and malignant melanoma. ZADAXIN is approved for sale in select markets internationally, most notably in China where SciClone has an established sales and marketing operation. A key part of SciClone's strategy is to leverage its advantage and broaden its portfolio in the rapidly growing Chinese market by in-licensing or acquiring the marketing rights to other products, such as DC Beadâ„¢. For the U.S. market, SciClone's other clinical-stage drug development candidates are RP101 for the treatment of pancreatic cancer and SCV-07 for the treatment of hepatitis C. For more information about SciClone, visit www.sciclone.com.
The information in this press release contains forward-looking statements including our expectations and beliefs regarding future sales and financial results for 2007, and progress and results of our clinical trials. Words such as "expects," "plans," "believe," "may," "will," "anticipated," "intended" and variations of these words or similar expressions are intended to identify forward-looking statements. In addition, any statements that refer to expectations, goals, projections or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. These statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions that are difficult to predict. Therefore, our actual results could differ materially and adversely from those expressed in any forward-looking statements as a result of various factors, including future actions by the U.S. Food and Drug Administration, or equivalent regulatory authorities in Europe, the fact that experimental data and clinical results derived from studies with a limited group of patients may not be predictive of the results of larger studies, the progress or failure of clinical trials, our actual experience in executing on our objectives, the performance of our partners, maintenance of the sufficiency and eligibility of the enrolled patient population, unanticipated delays or additional expenses incurred during our clinical trials, our future cash requirements, delays in analyzing and synthesizing data obtained from clinical trials, the performance and future actions of our strategic partners, unexpected delays in clinical trial enrollment, , as well as other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission. Further, although our financial guidance is based on our current estimates, factors such as the actual timeline and design of the phase 3 melanoma clinical trial and final decisions regarding expense sharing arrangements for the trial could alter the estimates of our research and development expenses, net loss and year-end cash balance for 2007.
Contact: Corporate Contact: Richard Waldron Executive Vice President and Chief Financial Officer SciClone Pharmaceuticals, Inc. 650-358-3437Â