SciClone Pharmaceuticals, Inc. announced that the Company and the U.S. Food and Drug Administration (FDA) have reached agreement on the design of a phase 3 registration trial for thymalfasin as a potential treatment for stage IV melanoma

 Based on the FDA's review, the agency agrees that the design and planned analysis of SciClone's study adequately addresses the objectives necessary to support a regulatory submission.

"Patients suffering from stage IV melanoma have very few treatment options available. Based on the positive data from an earlier phase 2 trial, thymalfasin could provide new treatment modalities for this high unmet medical need," said Israel Rios, MD, SciClone's Chief Medical Officer. "The FDA's acceptance of our phase 3 protocol for thymalfasin for the treatment of stage IV melanoma, the most advanced form of skin cancer, is a critical step in the advancement of this clinical program. We are now able to chart the best course going forward, which may include bringing on a development partner."

The phase 2 multi-center, randomized open-label study enrolled 488 patients with stage IV 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 stage IV 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. For more information on this phase 2 trial, please refer to SciClone's press release dated June 4, 2007.

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.