Navidea Biopharmaceuticals, Inc. announced that based on its very recent meeting with the US Food and Drug Administration (FDA), the company will begin the clinical trial development process for its intravenous (IV) injection protocols for use of Lymphoseek (technetium Tc 99m tilmanocept) injection in rheumatoid arthritis (RA) and other disease states. Lymphoseek is Navidea’s first commercial product from its Manocept platform.

“Our efforts to continue to unlock the significant value of the Manocept platform are well underway as we seek to expand Lymphoseek’s label so it can be used as an immunodiagnostic for additional diseases,” said Rick Gonzalez, president and CEO of Navidea. “This collaborative meeting with FDA has enabled us to continue to advance the regulatory process and begin to implement our clinical program in rheumatoid arthritis, an indication that has an addressable market that is substantially larger than the current Lymphoseek indications. We look forward to reporting our progress throughout the year.”

Over the past year Navidea conducted a series of meetings and communications with the FDA to gain clarity on a path to extend the current Lymphoseek IND to support IV administration of Lymphoseek. In parallel the company initiated its clinical development efforts and has already completed six required non-clinical animal studies for this new route of administration, submitted the summary results in a briefing package to the FDA, and secured NIH grants in RA and Kaposi’s Sarcoma, worth up to $3.8 million to support further development through phase 2 studies.

Based upon the feedback from the latest meeting, Navidea expects to submit an IND amendment to the FDA that will allow initiation of phase 1/2 IV studies of Lymphoseek. The addition of this new route of administration would enable further development of Lymphoseek in broader immunodiagnostic disease applications including rheumatoid arthritis. The timing is expected to be consistent with Navidea’s previously disclosed development plans to initiate a multi-center phase 1/2 registrational trial employing IV-administration to evaluate Lymphoseek for the primary diagnosis of rheumatoid arthritis and to aid in the differential diagnosis of rheumatoid arthritis from other types of inflammatory arthritis during the second half of 2016. In addition, we expect to begin the phase 1 pilot trial evaluating subcutaneous injection of Lymphoseek in active RA subjects in the second quarter of 2016.

Lymphoseek (technetium Tc 99m tilmanocept) injection is the first and only FDA-approved receptor-targeted lymphatic mapping agent. It is a novel, receptor-targeted, small-molecule radiopharmaceutical used in the evaluation of lymphatic basins that may have cancer involvement in patients. Lymphoseek is designed for the precise identification of lymph nodes that drain from a primary tumour, which have the highest probability of harboring cancer. Lymphoseek is approved by the US Food and Drug Administration (FDA) for use in solid tumour cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, melanoma or squamous cell carcinoma of the oral cavity. Lymphoseek has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity.

Accurate diagnostic evaluation of cancer is critical, as results guide therapy decisions and determine patient prognosis and risk of recurrence. Overall in the US, solid tumour cancers may represent up to 1.2 million cases per year. The sentinel node label in the US and Europe may address approximately 600,000 new cases of breast cancer, 160,000 new cases of melanoma and 100,000 new cases of head and neck/oral cancer diagnosed annually.

Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management; guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.

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). In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1 per cent).