Navidea: Positive Data in Phase 2B Trial of Tilmanocept Imaging

American biotechnology company Navidea Pharmaceuticals (NYSE: NAVB) has announced positive preliminary data from a second interim analysis from its phase 2b NAV3-31 clinical trial, “Evaluation of the Precision and Sensitivity of Tilmanocept Uptake Value (TUV) on Tc99m Tilmanocept Planar Imaging,” which is currently evaluating the utility of Tc99m tilmanocept imaging in the clinical monitoring of patients with rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder that affects over 1.3 million people in the United States.

“This second interim analysis was designed to examine data from Arm 3 of the study in order to evaluate the magnitude of change of Tc99m tilmanocept signal localized to RA-involved joints in patients before and after treatment with an anti-TNF alpha therapy as well as to examine whether this change in localization, if any, can serve as an early, quantifiable predictor of treatment efficacy,” Navidea Pharmaceuticals stated in their press release.

“Analysis demonstrates that these interim data further corroborate Navidea’s hypotheses that Tc99m tilmanocept imaging can provide robust, quantitative imaging in healthy controls and in patients with active rheumatoid arthritis (“RA”), and that this imaging can provide an early indicator of treatment efficacy in patients with active RA,” the company stated.

Navidea’s Chief Medical Officer Michael Rosol stated, “We are encouraged by these interim results, which are in line with our hypotheses, support the continuation of the current Phase 2B study, and will be fundamental to speaking with the FDA about moving forward into the Phase 3 trial later this year.”

“We are excited that we are on track to possibly providing rheumatologists and those suffering with RA a noninvasive, quantifiable, early indicator of whether or not an anti-TNF alpha treatment is working. This could bring enormous benefit to these patients by assisting physicians in putting them on the right course of treatment earlier than would otherwise be possible today,” Dr. Rosol continued.

CEO of Navidea Navidea Jed Latkin stated, “I am once again very pleased that the interim results of our ongoing Phase 2B study are so encouraging. These data support our belief that Tc99m tilmanocept imaging has the potential to provide an early and accurate indication of treatment effectiveness to rheumatologists, allowing them to tailor effective treatment regimens for RA patients. We are looking forward to continuing our progress into a Phase 3 study.”

The NAV3-31 trial consists of three patient cohorts: healthy controls, RA patients receiving “stable” treatment for active moderate-to-severe disease, and patients with moderate-to-severe RA treated with antibody targeting the cytokine tumor necrosis factor (TNF) alpha and monitored using Tc99m Tilmanocept imaging. The third group constitutes a “pilot arm of the upcoming Phase 3 trial.”

The second interim analysis of the Navidea phase 2b trial included 15 subjects with active moderate-to-severe RA treated with anti-TNF alpha. Planar gamma imaging and clinical assessments were completed prior to and 5 weeks after the initiation of immunotherapy in all patients, and 8 subjects additionally received imaging and clinical evaluation at 12 weeks post-initiation.

The data suggested “a wide dynamic range of more than one order of magnitude (>10-fold) for calculated global Tc99m tilmanocept uptake values in joints with RA-involved inflammation.”

Tc-99m tilmanocept is a diagnostic radiopharmaceutical imaging agent that consists of multiple units of diethylenetriaminepentaacetic acid (DTPA) and mannose. The material selectively binds to the mannose receptor CD206, a protein expressed on the surface of macrophages, and has been used for the imaging of lymph nodes and tumors in addition to structures associated with RA.

“In the subjects with 12-week follow up data available, global Tc99m tilmanocept signals declined by an average of 58% from baseline to week 5 in those who responded significantly to anti-TNF alpha treatment by week 12. In those subjects who did not have a significant clinical response to anti-TNF alpha treatment by week 12, Tc99m tilmanocept signals increased by an average of 79% from baseline to 5 weeks. These preliminary results indicate that marked changes in Tc99m tilmanocept global uptake values by week 5 are in agreement with clinical efficacy evaluations made at week 12 of treatment,” Navidea stated in the press release.

“The wide dynamic range of global Tc99m tilmanocept signal readout combined with the low variability of imaging signal quantification established in Arms 1 and 2 of this trial are supportive of the idea that clinically meaningful changes in signal localization can be detected,” the company continued.

According to Navidea, “Tc99m tilmanocept imaging from baseline to week 5 was predictive of clinical outcome at 12 weeks in 7 out of 8 subjects with 12-week clinical assessment available at the time of the interim analysis. The one subject who did not demonstrate concordance of signal quantification and clinical assessment had undergone a change in treatment regime while enrolled in the trial that may have impacted the trajectory of the clinical response.”

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