Navidea Biopharmaceuticals, Inc., a biopharmaceutical company focused on the development and commercialization of precision diagnostics and radiopharmaceutical agents,  has received notification from the United States Food and Drug Administration (FDA) that the Prescription Drug User Fee Act (PDUFA) date for 99m-Tc-Tilmanocept (Lymphoseek), has been modified to September 10, 2012, a 90-day extension from the initial PDUFA date of June 10. Lymphoseek is an investigational, proprietary radioactive tracing agent for lymphatic mapping and lymphoscintigraphy.

As part of its ongoing support of the Lymphoseek NDA review, on March 30, 2012, the company provided as requested by the Agency, updated chemistry, manufacturing and control information related to one of several drug analytical assays. As this information was submitted within the 90-day period prior to the PDUFA date, on April 2nd, FDA at its option elected to extend the review period by 90 days to complete a first-cycle evaluation. Neither this FDA decision nor the NDA review-to-date has raised questions on Lymphoseek's safety or efficacy. The PDUFA date extension does not pertain to the company's ongoing head and neck cancer clinical trial or to the recently announced comparative analysis of Lymphoseek to sulfur colloid.

“We have submitted the information requested by the FDA in support of a first-cycle review of the Lymphoseek NDA,” said Mark Pykett, Navidea president and CEO. “Our focus continues to be on supporting the FDA review and preparing for anticipated market introduction of Lymphoseek. All of the clinical data we have generated for Lymphoseek to date support a clear safety and efficacy profile, which we believe holds value to patients and their physicians.”

Lymphoseek is a proprietary radioactive tracing agent being developed for use in connection with gamma detection devices in pre-operative lymphoscintigraphy imaging and in a surgical procedure known as Intraoperative Lymphatic Mapping. Lymphoseek works by binding to a specific receptor found on the surface of dendritic cells and macrophages, which reside in high concentration in lymph nodes. This receptor-targeted property of Lymphoseek enables it to attach to and remain within lymph nodes.

Two phase III multi-centre clinical trials for Lymphoseek in patients with breast cancer or melanoma have concluded. A third phase III clinical study to evaluate the efficacy of Lymphoseek as a sentinel lymph node tracing agent in patients with head and neck squamous cell carcinoma is currently ongoing. To date Lymphoseek is the first and only receptor-targeted agent developed specifically for ILM.

The Lymphoseek NDA submitted by the company in August 2011 includes results from two complete phase III studies of Lymphoseek, NEO3-05 and NEO3-09, performed in patients with either breast cancer or melanoma. The primary endpoint for both the NEO3-05 and NEO3-09 studies was the concordance (or the rate of agreement) on a lymph node count basis of Lymphoseek with vital blue dye, a long-standing, FDA-approved, on-label agent for lymphatic mapping and appropriate "Truth Standard" comparator for registration purposes. In both of the phase III studies (NEO3-05, NEO3-09), the concordance of Lymphoseek to vital blue dye was highly statistically significant (p<0.0001).

Lymphoseek met all primary and secondary endpoints across both studies. Secondary endpoints were also assessed, including the false negative rate (or failed detection rate) of Lymphoseek versus vital blue dye. This analysis evaluated the ability of vital blue dye and Lymphoseek to detect lymph nodes that potentially contained cancer cells, as determined by pathology evaluation. In both studies combined, vital blue dye exhibited a failed lymph node detection rate of more than 20%, whereas Lymphoseek showed a failed lymph node detection rate of approximately 1%, or twenty-fold lower than vital blue dye, a difference that was also highly statistically significant (p<0.002). Because the key objective of performing ILM is to potentially identify cancer cells when they are present in lymph nodes, reduction of the failed lymph node detection rate is important.

In more than 500 subjects receiving Lymphoseek to date, including those studied as a part of the NEO3-05 and NEO3-09 studies, no drug-related serious adverse events or clinically significant drug-related adverse events have been reported.