The FDA has granted a Fast Track designation to Lymphoseek (technetium Tc99m tilmanocept) as a radioactive diagnostic imaging agent for sentinel lymph node detection in patients with head and neck cancer. One week after receiving this designation, Navidea Biopharmaceuticals, Inc., the company developing the injection, announced that it had submitted a supplemental new drug application (sNDA).
The Lymphoseek injection is a novel small-molecule radiopharmaceutical used in lymphatic mapping process to aid in the diagnostic evaluation of potential cancer spread prior to surgery. The drug is injected into the tumor area and later, using a handheld radiation detector, helps to identify lymph nodes that have taken up the agent’s radioactivity.
The FDA initially approved the injection for patients with breast cancer or melanoma in March 2013. At the time, the FDA stated that Lymphoseek was the first new drug to gain approval specifically for lymph node mapping in more than 30 years.
“Today, many patients may undergo unnecessary full regional lymph node dissection, which removes an entire chain of lymph nodes, in order to see if cancer has spread from the primary tumor into the lymphatic system,” Stephen Y. Lai, MD, PhD, FACS, associate professor, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center and a lead investigator on the NEO3-06 phase III trial, the basis for the Fast Track designation and sNDA, said in a statement.
The phase III NEO3-06 trial examined the diagnostic tool in more than 80 patients with head and neck cancer and intraoral squamous cell carcinoma. Following administration of Lymphoseek, a multiple level lymph node dissection was performed on each patient to explore the false positive rates associated with the identification of sentinel lymph nodes.
Lymph node dissection revealed that 39 patients in the trial had pathologically positive lymph nodes. The Lymphoseek Injection correctly identified 38 of the 39 patients with positive lymph notes, representing a false negative rate of 2.56% (P
For the 39 patients with positive nodes, standard multiple level nodal dissection led to the removal of an average of 38 lymph nodes per patient. However, the utilization of Lymphoseek in the trial indicated the removal of only 4 lymph nodes on average per patient. No differences were reported in the accuracy of Lymphoseek when surgery was performed the same-day or on a subsequent-day following injection.
“The ability of Lymphoseek to accurately identify sentinel lymph nodes in these patients, such as demonstrated in the NEO3-06 phase III study, may not only improve diagnostic accuracy, but also make the procedure more efficient and minimize the morbidity and side effects associated with more extensive regional dissections,” Lai said.
The trial’s secondary endpoints included the determination of sensitivity (97.6%), negative predictive value (97.8%), and overall accuracy (98.8%) relative to the pathology status of non-sentinel lymph nodes.
The safety of Lymphoseek was also evaluated through observation of adverse events, clinical laboratory tests, vital signs, electrocardiograms, and physical examinations. There were 13 serious adverse events in the trial, though none were associated with Lymphoseek. Additionally, there were no deaths associated with the NEO3-06 trial. The most common side effects associated directly with Lymphoseek in clinical trials are pain or irritation at the injection site.
“If this sNDA is approved, Lymphoseek will be the only approved agent for SLN detection in this patient population, and representing another step forward in Navidea’s efforts to develop precision diagnostics that improve the accuracy of diagnosis,” Mark Pykett, VMD, PhD, Navidea CEO, said in a statement.
In addition to the already approved indications and in head and neck cancer, Navidea is also developing Lymphoseek in prostate cancer, thyroid cancer, lung cancer, and colorectal cancer.