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. Full Lymphoseek prescribing information can be found at www.lymphoseek.com

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) and intra-operative lymphatic mapping (ILM).  

In addition to Phase 3 clinical trials in breast cancer and melanoma which supported the Lymphoseek approval, Navidea is conducting an additional Phase 3 clinical trial in patients with head and neck cancer. This trial reached a pre-planned interim analysis point in 2013. 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 head or in the mouth, as compared to the removal of all lymph nodes during multiple level nodal dissection surgery of the head and neck. Following the completion of the full dataset and secondary analyses of the head and neck trial, Navidea will evaluate the possibility of filing a Supplemental New Drug Application (sNDA) late in 2013. Additional studies of Lymphoseek in other cancer types by the company or by investigators are also anticipated.

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.