SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) and Sigma-Tau S.p.A. today announced positive interim survival data from a large phase 2 trial treating patients with stage IV malignant melanoma, the most advanced form of this cancer. Data from the first four arms of this ongoing five-arm trial showed that the addition of 3.2 mg of ZADAXIN® (thymalfasin or thymosin alpha 1) to standard dacarbazine (DTIC) chemotherapy increased the median survival to 10.2 months. These data compare favorably to the median survival of 6.6 months for patients treated with DTIC chemotherapy with interferon alpha. DTIC is the only approved therapy in the United States for the treatment of advanced melanoma. In addition, data show patients treated with thymalfasin and DTIC chemotherapy without interferon alpha achieved more than double the overall tumor response as compared to the control group, consistent with previously reported interim results. SciClone and Sigma-Tau expect to present detailed clinical results from this trial including statistical analyses at the upcoming ASCO meeting.
"Based on the strength of these data, we and Sigma-Tau plan to meet with U.S. and European regulatory authorities to discuss a phase 3 clinical trial design using ZADAXIN and DTIC chemotherapy," commented Friedhelm Blobel, Ph.D., Chief Executive Officer of SciClone Pharmaceuticals, Inc. "We are pleased that the addition of ZADAXIN to the current standard of care may offer survival benefits to patients diagnosed with this life-threatening cancer."
"We are excited to observe the positive effects on survival and overall tumor response when ZADAXIN is added to standard DTIC chemotherapy in treating patients with malignant melanoma," commented Roberto Camerini, M.D., Research and Development for Sigma-Tau S.p.A. "Current therapy for the advanced stages of this cancer provides minimal survival benefit for the patient. We are particularly encouraged of the prospect of improving patient survival with the addition of thymalfasin, a drug shown to be safe and well tolerated in several other clinical settings."
Survival data announced today included results from 386 patients from the first four arms of this five-arm phase 2 clinical trial. When measured for survival, all patients in the treatment arms containing thymalfasin reached a longer median survival than those in the control arm. Patients treated with thymalfasin in combination with DTIC without interferon alpha reached a median survival of 10.2 months, compared to 6.6 months for patients in the control group treated with DTIC and interferon alpha. The fifth arm of the clinical trial, treating patients with thymalfasin 6.4 mg plus DTIC and interferon alpha, was initiated later than the other arms. Patients in the fifth arm have recently completed therapy and continue to be followed according to the protocol.
Median Survival Treatment Arm N= (Months) DTIC + interferon alpha (Control) 94 6.6 ZADAXIN 3.2 mg + DTIC 98 10.2 ZADAXIN 1.6 mg + DTIC + interferon alpha 97 9.9 ZADAXIN 3.2 mg + DTIC + interferon alpha 97 8.8
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 natural killer (NK) cells and cytotoxic T lymphocytes (CTL). It has recently been suggested that a broad immune response is beneficial, due to the extensive variation of different tumor cell types. It is also important to increase the presentation of cancer-specific antigens to the immune system through sustained expression of 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 broad activation of various arms of the immune system, including increases in NK cells, CTLs, and expression of MHC Class I. 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 the Malignant Melanoma Trial
SciClone's European partner, Sigma-Tau, is conducting a large, randomized, open-label phase 2 trial at 64 clinical sites throughout Europe evaluating different dose levels of thymalfasin in combination with DTIC chemotherapy with and without low-dose interferon alpha as a first-line treatment for patients with stage IV malignant melanoma. Most of these stage IV patients have visceral metastases and the remaining patients have lung metastases and skin or lymph node metastases.
The trial's primary endpoint is overall tumor response. Secondary endpoints include overall survival, duration of response, time to disease progression and immunological response. The trial is not powered with sufficiently large sample size to show statistical significance of the secondary endpoints including survival. Analyses of the complete data will determine the significance of the final results regarding the secondary endpoints.
Thymalfasin received Orphan Drug Status in the United States for stage IIb through stage IV malignant melanoma in March 2006.
About Malignant Melanoma
The American Cancer Society estimates that this year in the United States approximately 7,700 deaths will occur from melanoma. Melanoma is classified as stage IV, the most advanced form, once the cancer has spread beyond the skin to a distant site. Current therapies 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.
Sigma-Tau is a privately held, research focused pharmaceutical company headquartered in Pomezia (Rome), Italy. In 2005, Sigma-Tau had revenues of 674 million euros (US$ 900 million). Sigma-Tau has 2,400 employees, 400 of whom work in the research and development of products for therapeutic areas including cardiovascular, metabolism, central and peripheral nervous system, immunology and oncology. A particularly significant example of Sigma-Tau's work in oncology is "Gimatecan," a novel oral anticancer compound. In a major agreement in 2003, Sigma-Tau licensed the worldwide development and marketing rights for Gimatecan to the Swiss multinational drug company Novartis.
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. SciClone's other drug development candidate is SCV-07, currently in early clinical development in the U.S. for the treatment of viral infectious diseases. 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 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 ZADAXIN, unexpected adverse results to patients, future actions by the U.S. Food and Drug Administration or equivalent regulatory authorities in China and Europe and the fact that experimental data and clinical results derived from pre-clinical studies or from studies with a limited group of patients may not be predictive of the results of larger studies, as well as other risks and uncertainties described in SciClone's filings with the Securities and Exchange Commission.
Chief Financial Officer
SciClone Pharmaceuticals, Inc.