Neoprobe’s New Drug Application (NDA) for Lymphoseek (tilmanocept), which was submitted on Aug. 10, has been accepted for review by the FDA.
The NDA submission from the Dublin, Ohio-based developer of oncology surgical and diagnostic products includes results from two Phase 3 studies of Lymphoseek, NEO3-05 and NEO3-09, performed in patients with either breast cancer or melanoma. The primary endpoint for both studies was the concordance 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 3 studies, 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 of Lymphoseek versus vital blue dye. This analysis evaluated the ability of vital blue dye and Lymphoseek to detect lymph nodes that contained cancer cells, as determined by pathology evaluation. In both studies combined, vital blue dye exhibited a failed detection rate of more than 20 percent, whereas Lymphoseek showed a failed detection rate of approximately 1 percent, 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 intraoperative lymphatic mapping is to identify cancer cells when they are present in lymph nodes, reduction of the failed 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.
Lymphoseek works by binding to a specific receptor found on the surface of dendritic cells and macrophages, which reside in lymph nodes. This receptor-targeted property of Lymphoseek enables it to attach to and remain within lymph nodes. To date Lymphoseek is the first and only receptor-targeted agent developed specifically for intraoperative lymphatic mapping.
"We now turn our focus toward preparing for next steps with the agency and a potential approval of Lymphoseek in the coming months, which according to FDA guidelines we anticipate will be late in the second quarter to third quarter of 2012," Mark Pykett, VMD, PhD, Neoprobe president and CEO, said in a statement.