Lymphoseek® – A Receptor-Targeted Agent for Lymphatic Mapping
On March 13, 2013, the US FDA approved Lymphoseek® (technetium Tc 99m tilmanocept) Injection for use in lymphatic mapping procedures to assist in the localization of lymph nodes draining a primary tumor in patients with breast cancer or melanoma. Lymphoseek was also approved by the FDA in June 2014 to guide sentinel lymph node biopsy, in patients with clinically node negative squamous cell carcinoma (SCC) of the oral cavity.
Lymphoseek® (Technetium Tc99m Tilmanocept) Injection is a first-in-class mannose receptor (CD206) binding radiopharmaceutical agent developed for use in external lymph node imaging (lymphoscintigraphy), intra-operative lymphatic mapping (ILM) and sentinel lymph node biopsy.
In addition to Phase 3 clinical trials in breast cancer and melanoma which supported the Lymphoseek approval, Navidea completed an additional Phase 3 clinical trial in patients with head and neck cancer. Positive topline results demonstrated that Lymphoseek met the primary efficacy endpoint of accurately identifying sentinel lymph nodes (SLNs) in subjects with squamous cell carcinoma of the oral cavity, as compared to the removal of all lymph nodes during multiple level nodal dissection surgery of the head and neck. Additional studies of Lymphoseek in other cancer types by the company or by investigators are either anticipated or ongoing.
Navidea submitted a Marketing Authorization Application (MAA) for Lymphoseek® to the European Medicines Agency (EMA) in December 2012.
How Might Lymphoseek Be Used?
Intra-operative lymphatic mapping, together with lymphoscintigraphy, has become the cancer diagnostic evaluation procedure of choice for oncology surgeons as the information provided helps them focus on high-risk nodes and reduces patient exposure to unnecessary surgical complications. During an ILM procedure, a radioactive tracing agent, such as Lymphoseek, is injected at the site of the primary tumor and follows the drainage path of the tumor to the nearest lymph node or nodes. After injection of the radioactive agent, external gamma detection-based imaging can be performed to assist in the pre-operative localization of nodes. A gamma detection device is then used to track the pathway of the tracing agent. Lymph nodes in the potential drainage path are identified using the radioactive tracing agent.
Oncologists generally believe that if nodes that first drain the primary tumor show no sign of malignancy, the downstream nodes are likely to be clear of disease, and the removal of other nearby lymph nodes is clinically unnecessary. The ability to rapidly locate and biopsy lymph nodes provides vital information to the physician in determining if the cancer has spread or if it is localized to the site of the primary tumor and, therefore, enables surgical management to be tailored specifically to each patient’s burden of disease.
Important Lymphoseek Safety Information: In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs). Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection. Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers. In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (
Full Lymphoseek prescribing information can be found at www.lymphoseek.com