生物制药公司Immunomedics 6月9日宣布，FDA已授予实验性药物IMMU-132治疗胰腺癌的孤儿药地位。IMMU-132是一种抗体药物偶联物（antibody-drug conjugate，ADC），开发用于实体瘤的治疗。ADCs是一类将抗癌制剂偶联于抗体的药物，与传统的治疗药物相比，ADCs能杀死肿瘤细胞，同时副作用较少。

根据近期公布于美国癌症协会胰腺癌特别会议上的数据，13例既往已接受1-5种疗法的胰腺癌患者，接受IMMU-132治疗后，疾病无进展生存期（PFS）达到了12.7周（范围4.3-21.4周），而该患者组在接受最后一次治疗后，预计的平均PFS仅为8周（范围4-36周）。

这是FDA授予IMMU-132的第二个孤儿药地位。此前，FDA已授予IMMU-132治疗小细胞肺癌的孤儿药地位。在一项正在开展的I/II期临床试验中，IMMU-132在大肠癌、食管癌、三阴性乳腺癌、小细胞肺癌和非小细胞肺癌患者群体中取得了部分响应。

关于IMMU-132：

IMMU-132是一种由人源化单抗hRS7和抗癌药物SN-38偶联而成的抗体药物偶联物（ADC）。hRS7能够结合滋养层细胞表面抗原（TROP-2，又名上皮糖蛋白-1抗原，EGP-1）。TROP-2大量表达于多种人类肿瘤细胞表面，如乳腺癌、宫颈癌、结直肠癌、肾癌、肝癌、肺癌、胰腺癌、前列腺癌等，但在正常人体组织中的表达有限。hRS7结合TROP-2后，能够内化进入肿瘤细胞内部，使其成为一种合适的细胞毒性药物递送工具。

SN-38是抗癌药伊立替康（irinotecan）的活性代谢产物。伊立替康是治疗转移性结直肠癌的标准疗法，但具有很大的肠胃道和血液毒性。通过将SN-38偶联至肿瘤靶向性抗体，递送SN-38至肿瘤，可能能够成倍增加药效，同时降低系统性毒性。临床前研究表明，与伊立替康相比，IMMU-132能够递送剂量高达120倍的SN-38至人类胰腺异种移植物中。在人类癌症的各种动物模型中，IMMU-132显著改善了生存率及肿瘤消退。

英文原文：Immunomedics Announces Orphan Drug Designation for IMMU-132 for Pancreatic Cancer Therapy

MORRIS PLAINS, N.J., June 9, 2014 (GLOBE NEWSWIRE) -- Immunomedics, Inc., (Nasdaq:IMMU) today announced that IMMU-132, the Company's antibody-drug conjugate (ADC) for solid cancer therapy, has received orphan drug status from the Office of Orphan Products Development of the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer.

"This is the second orphan designation from FDA for IMMU-132, which has demonstrated activity in patients with advanced pancreatic cancer, as well as partial responses in 5 other types of solid cancer," commented Cynthia L. Sullivan, President and Chief Executive Officer.

As recently reported by the Company at the American Association for Cancer Research Special Conference on Pancreatic Cancer: Innovations in Research and Treatment, 13 pancreatic cancer patients who had failed 1-5 prior therapies showed a median time-to-progression of 12.7 weeks (range 4.3-21.4 weeks) after receiving repeated doses of IMMU-132. This compared favorably with the median 8.0 weeks (range 4-36 weeks) estimated from the patients' last prior therapy.

IMMU-132 has also been designated an orphan drug by FDA for the treatment of patients with small-cell lung cancer. In an ongoing Phase I/II clinical study, IMMU-132 has resulted in partial responses in patients with colorectal cancer, esophageal cancer, triple negative breast cancer, and small-cell and non-small-cell lung cancers.

Orphan drug status is granted by FDA to a drug or biological product to treat a rare disease or condition upon request of a sponsor. Orphan drug designation qualifies the Company for various development incentives, including tax credits for qualified clinical testing, a waiver from FDA's application User Fee for marketing application, and a seven-year period of marketing exclusivity in the United States for IMMU-132, if it is approved by FDA for the treatment of patients with pancreatic or small-cell lung cancer.

The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Safety and effectiveness of a drug must be established through adequate and well-controlled studies.

About IMMU-132

IMMU-132 is composed of hRS7, a humanized antibody that binds to the trophoblast cell-surface antigen (TROP-2), also known as the epithelial glycoprotein-1 antigen (EGP-1). TROP-2 is expressed by many human tumors, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. The antibody, hRS7, internalizes into cancer cells following binding to TROP-2, making it a suitable candidate for the delivery of cytotoxic drugs.

SN-38 is the active metabolite of irinotecan, which is a standard therapy for patients with metastatic colorectal cancer, but has major gastrointestinal and hematologic toxicity. By attaching SN-38 to tumor-targeting antibodies, delivery of SN-38 to the tumor may be increased several-fold while mitigating systemic toxicity. Preclinical studies have indicated that IMMU-132 delivers 120-times the amount of SN-38 to a human pancreatic tumor xenograft than when irinotecan is given. In various animal models of human cancers, IMMU-132 significantly improved survival and tumor regression.

About Immunomedics

Immunomedics is a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer, autoimmune disorders and other serious diseases. Immunomedics' advanced proprietary technologies allow the Company to create humanized antibodies that can be used either alone in unlabeled or "naked" form, or conjugated with radioactive isotopes, chemotherapeutics, cytokines or toxins. Using these technologies, Immunomedics has built a pipeline of nine clinical-stage product candidates. Immunomedics has an ongoing collaboration with UCB, S.A. (UCB), who has worldwide rights in non-cancer indications to Immunomedics' Phase III product candidate, epratuzumab. UCB expects Phase III data in systemic lupus erythematosus (SLE) in the first quarter of 2015. Immunomedics is exploring epratuzumab in oncology in collaboration with outside cancer study groups. Immunomedics' most advanced wholly owned candidate is 90Y-clivatuzumab tetraxetan, which is in an ongoing Phase III registration trial in patients with pancreatic cancer. Immunomedics' portfolio of wholly owned product candidates also includes antibody-drug conjugates (ADCs) that are designed to deliver a specific payload of a chemotherapeutic directly to the tumor while reducing overall toxicity effects that typically occur when these chemotherapeutic agents are dosed alone. Immunomedics' most advanced ADCs are IMMU-132 and IMMU-130, which are in Phase I/II trials for a number of solid tumors and metastatic colorectal cancer (mCRC), respectively. Immunomedics also has a number of other product candidates that target solid tumors and hematologic malignancies, as well as other diseases, in various stages of clinical and pre-clinical development. These include bispecific antibodies which have application as T-cell redirecting immunotherapies targeting cancers and infectious diseases as well as next-generation therapies in cancer and autoimmune disease. Immunomedics creates these bispecific antibodies using its patented DOCK-AND-LOCK™ (DNL™) protein conjugation technology. The Company believes that its portfolio of intellectual property, which includes approximately 248 active patents in the United States and more than 400 foreign patents, protects its product candidates and technologies. Immunomedics' strength in intellectual property has resulted in the top-4 ranking in the January 2014 Patent Board scorecard in the Biotechnology industry.