Press Release: SciClone and Sigma-Tau Report Thymalfasin Meets Primary Endpoint in Phase 2
SciClone and Sigma-Tau Report Thymalfasin Meets Primary Endpoint in Phase 2 Malignant Melanoma Trial Data Presented at Annual Meeting of the American Society of Clinical Oncology SAN MATEO, CA - SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) and Sigma-Tau S.p.A today announced that SciClone's lead product candidate thymalfasin (ZADAXINÂ®, thymosin alpha 1) achieved its primary endpoint in a phase 2 clinical trial treating patients diagnosed with stage IV malignant melanoma, the most advanced form of skin cancer. Results showed that thymalfasin in combination with dacarbazine (DTIC) chemotherapy tripled the overall response rate and extended overall survival by nearly 3 months compared to patients treated with DTIC, the current standard of care, and interferon alpha. "We are extremely pleased with the outcome of this trial, and are particularly excited that thymalfasin's therapeutic effect is demonstrated consistently through increased overall survival, the most important standard in oncology as well as tumor response in each treated group," commented Israel Rios, M.D., Chief Medical Officer of SciClone Pharmaceuticals, Inc. "Based on these results, we intend to meet with the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) in the third quarter of 2007. Our current goal is to begin our planned phase 3 registration trial in the fourth quarter of 2007 to treat stage IV malignant melanoma patients." The phase 2 multi-center, randomized open-label study enrolled 488 patients with stage IV metastatic melanoma at 64 European clinical sites. The trial was designed to evaluate different dose levels of thymalfasin in combination with DTIC chemotherapy, with and without low-dose interferon alpha, as a first-line treatment for malignant melanoma. Most patients enrolled in the trial had liver and other metastases and the remaining patients had lung metastases and skin or lymph node metastases. Thymalfasin at all dose levels was well-tolerated in all treated patients, with no serious adverse events attributed to the drug. These data were presented Sunday, June 3rd, 2007 at the Annual Meeting of the American Society of Clinical Oncology in Chicago, Illinois and were the subject of a poster presentation entitled 'A large first-line, randomized, dose-finding, phase II study on Thymosin alpha 1 (TÎ±1) plus Dacarbazine (DTIC) with or without Interferon alpha (IFNÎ±) vs DTIC plus IFNÎ± in stage IV melanoma. Tumor response and survival results' (ASCO abstract number: 8535). Tumor Response Data When measured for overall tumor response, including complete response (CR) and partial response (PR), all patients in the treatment arms containing thymalfasin showed a greater overall tumor response than those in the control arm. Patients treated with the 3.2 mg dose of thymalfasin in combination with DTIC without interferon alpha showed an overall tumor response of 12.1%, compared to 4.1% for patients in the control group treated with DTIC and interferon alpha Overall Survival and Progression Free Survival Data When measured for overall survival, all patients in the treatment arms containing thymalfasin reached a longer median survival than those in the control arm. Patients treated with the 3.2 mg dose of thymalfasin in combination with DTIC without interferon alpha reached a median survival of 9.3 months, compared to 6.6 months for patients in the control group treated with DTIC and interferon alpha. Median progression free survival was 1.87 months for the group of patients treated with the 3.2 mg dose of thymalfasin in combination with DTIC without interferon alpha, compared to 1.81 months for the control group treated with DTIC and interferon alpha. Even though the median progression free survival times were similar, the Hazard Ratio (HR) comparing 3.2 mg of thymalfasin together with DTIC versus patients treated with DTIC and interferon alpha was 0.74, which translates into a 26% reduction of the risk of disease progression for patients treated with 3.2 mg of thymalfasin. In a subset analysis excluding patients with elevated levels of the enzyme lactate dehydrogenase (LDH), a factor associated with poor prognosis, the group of patients with normal LDH levels treated with the 3.2 mg dose of thymalfasin in combination with DTIC without interferon reached a median survival of 14.4 months, compared to 10.8 months for the control group treated with DTIC and interferon alpha. Median progression free survival was 3.65 months for the group of normal LDH patients treated with the 3.2 mg dose of thymalfasin in combination with DTIC without interferon alpha, compared to 2.17 months for the control group treated with DTIC and interferon alpha (HR= 0.62). How Thymalfasin Works in Melanoma Suppression of the growth of immune-sensitive tumors such as melanoma have been shown to be dependent on a strong immune response, including a large number of activated effectors such as tumor-infiltrating lymphocyte cells (TILs) and specific anti-melanoma cytotoxic T lymphocytes (CTL). It is also important to increase the presentation of cancer-specific antigens to the immune system through sustained expression of these molecules along with MHC Class I, as cancers avoid the immune system by decreases in this presentation. Thymalfasin's potential beneficial role in treatment of melanoma derives from its demonstrated activation of these various arms of the immune system, including increases in TILs, CTLs, and expression of MHC Class I and tumor-specific antigens. Thymalfasin's multiple activities arise through activation of Toll-like receptor 9 and signaling through increases in the nuclear factor NfKB through Myd88 and IKKb. Evaluation of thymalfasin's utility in melanoma animal models has confirmed effective anti-tumor activity. About Malignant Melanoma Skin cancer is the most common form of cancer in the United States. In 2007, The American Cancer Society estimates that approximately 8,110 deaths will occur from melanoma and another 59,940 cases of melanoma are expected to be diagnosed in this country. Melanoma is classified as stage IV, the most advanced form, once the cancer has spread beyond the skin to a distant site. DTIC and interleukin-2 (IL-2) are the only FDA-approved therapies for the treatment of malignant melanoma. However, these other therapeutic agents including alpha interferon, used alone or in combination, are ineffective at extending overall patient survival, which at this stage is typically only about six to nine months. Response to treatment largely depends upon the stage of melanoma, disease site and the extent to which the cancer has spread. ZADAXIN received Orphan Drug Designation in the United States for stage IIb through stage IV malignant melanoma in March 2006. About SciClone SciClone Pharmaceuticals is a biopharmaceutical company engaged in the development of therapeutics to treat life-threatening diseases. SciClone's lead product ZADAXIN is currently being evaluated in late-stage clinical trials for the treatment of malignant melanoma and hepatitis C. 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 in China by in-licensing or acquiring the marketing rights to other products, such as the DC Bead, to broaden its portfolio in this rapidly growing pharmaceutical market. For the U.S. market, SciClone's clinical-stage drug development candidates are SCV-07 for the treatment of viral infectious diseases and RP101 for the treatment of pancreatic cancer. 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 timing, 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. 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 the progress of ongoing and proposed trials and studies for thymalfasin, unexpected adverse results to patients, future actions by the U.S. Food and Drug Administration or equivalent regulatory authorities in Europe and the fact that clinical results from one study may not be indicative of clinical results in other large trials, as well as other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission.