FDA Fast Tracks sacituzumab govitecan for triple-negative breast cancer therapy

Previously, FDA also granted Fast Track status to sacituzumab govitecan for the therapy of patients with small-cell lung cancer

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MORRIS PLAINS, N.J.—Immunomedics, Inc., has received notice from the U.S. Food and Drug Administration (FDA) designating as a Fast Track development program the investigation of sacituzumab govitecan, the company's lead antibody-drug conjugate (ADC), for the treatment of patients with triple-negative breast cancer (TNBC) who have failed prior therapies for metastatic disease.
Sacituzumab govitecan (IMMU-132) is a novel ADC developed by Immunomedics by conjugating the moderately-toxic drug, SN-38, site-specifically and at a high ratio of drug to antibody. SN-38 is the active metabolite of irinotecan (Camptosar), which is used to treat certain solid cancers, particularly metastatic colorectal cancers, as a part of combination therapies, so its pharmacology and properties are well-known.
Based on the company's current results with patients having advanced TNBC, which is a serious and life-threatening disease for which there are few therapy options, as well as Immunomedics' clinical development plans for this ADC, the company gained this designation. Patients with TNBC enrolled to-date have had a median of four prior therapies (range, 1-15), including combinations of conventional and experimental drugs. To date, approximately 30 percent of assessable patients have shown an objective response rate (complete and partial remissions) by computed tomography, where shrinkage of tumors ranging from 30- to 100-percent has been observed. The major toxicity is neutropenia, which has been manageable by dose reductions or giving myeloid growth factors. Unlike the parent drug of SN-38 irinotecan, sacituzumab govitecan has not caused severe diarrhea.
The company is also evaluating this ADC in other solid tumors showing objective responses, such as in patients with small-cell and non-small cell lung, colorectal, esophageal and urinary bladder cancers.
Previously, FDA also granted Fast Track status to sacituzumab govitecan for the therapy of patients with small-cell lung cancer, which also constitutes an unmet medical need and where sacituzumab govitecan has induced objective responses. Sacituzumab govitecan has also been designated an orphan drug by FDA for the treatment of patients with small-cell lung or pancreatic cancers.
"We are pleased to receive this Fast Track designation from FDA," remarked Cynthia L. Sullivan, president and CEO. "We plan to discuss with FDA and our medical advisers the registration pathway for this valuable agent in breast cancer, and talks with potential licensing partners are continuing, We are close to completing enrollment of about 50 patients with metastatic TNBC, while we continue to study other indications as well," she added in a prepared statement.
The Fast Track programs, under the FDA Modernization Act of 1997, are designed to facilitate drug development and to expedite the review of new drugs that are intended to treat serious or life threatening conditions. Compounds selected must demonstrate the potential to address unmet medical needs. The Fast Track designation allows for close and frequent interaction with the agency. A designated Fast Track drug may also be considered for priority review with a shortened review time, rolling submission, and accelerated approval if applicable. The designation does not, however, guarantee approval or expedited approval of any application for the product.
TNBC represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20 percent of all invasive breast cancers and is more prevalent in young and African-American women. Despite the fact that initial responses with chemotherapy are high, TNBC characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. According to a published report, the median survival for patients with metastatic triple-negative breast cancer is estimated to be 13 months. Currently, there are no targeted treatments available for TNBC.
Sacituzumab govitecan 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 (Camptosar), which is a standard therapy for patients with metastatic colorectal cancer, but has major gastrointestinal and hematological toxicities. 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 sacituzumab govitecan delivers up to 135-times the amount of SN-38 to a human pancreatic tumor xenograft than when irinotecan is given. In various animal models of human cancers, the antibody-drug conjugate significantly improved survival and tumor regression.
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), to whom the company licensed epratuzumab for the treatment of all non-cancer indications worldwide. UCB expects Phase 3 data in systemic lupus erythematosus in the first half of 2015. Immunomedics is exploring epratuzumab in oncology in collaboration with independent cancer study groups. Immunomedics' most advanced candidate to which it retains worldwide rights for all indications is 90Y-clivatuzumab tetraxetan. The company initiated a Phase 3 registration trial in January 2014 in patients with advanced pancreatic cancer and expects topline data in mid-2016. 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 toxic effects that are usually found with conventional administration of these chemotherapeutic agents. Immunomedics' most advanced ADCs are sacituzumab govitecan (IMMU-132) and labetuzumab govitecan (IMMU-130), which are in Phase 2 trials for a number of solid tumors and metastatic colorectal cancer, 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 targeting cancers and infectious diseases as T-cell redirecting immunotherapies, as well as bispecific antibodies for next-generation cancer and autoimmune disease therapies, created using its patented DOCK-AND-LOCK(R) protein conjugation technology. The company believes that its portfolio of intellectual property, which includes approximately 261 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 a top-8 ranking in the Biotechnology industry by the Patent Board for the 2014 fiscal year.

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