Lymphoseek (technetium Tc 99m tilmanocept) Injection

Transcription

1 Lymphoseek (technetium Tc 99m tilmanocept) Injection A Novel Receptor-Targeted Lymphatic Mapping Agent Karen B. Randall, B.S., CNMT Navidea Biopharmaceuticals Medical Science Liaison

2 Lymphoseek (technetium Tc 99m tilmanocept) US Indication Lymphoseek (technetium Tc 99m tilmanocept) injection 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. Lymphoseek (technetium Tc 99m tilmanocept) injection Prescribing Information. Navidea Biopharmaceuticals. September ctober 2014 I 2

3 Lymphoseek (technetium Tc 99m tilmanocept) Important Safety Information 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). Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection. Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers. In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%). Please see full prescribing information at Lymphoseek (technetium Tc 99m tilmanocept) injection Prescribing Information. Navidea Biopharmaceuticals. September ctober 2014 I 3

4 Chemical Structure CH 2 Dextran Backbone - 2 C C - 2 N N - 2 C - 2 C H H S NH N 99m Tc ND CH2 H H S H 2 N NC HN CH 2 H H S NH NM S H H DTPA - Chelator H H Sondak VK, et al. Ann Surg ncol. 2013;20(2): Wallace AM, et al. Ann Surg ncol. 2013;20(8): Mannose - Ligand 4

5 Volume and Route of Administration Tc 99m tilmanocept may be administered as a single injection or multiple injections Planned Number of Injections for a Patient Total Injection Volume Per Patient Reconstituted Vial Volume of Tc 99m tilmanocept 1 syringe x 0.1 ml 0.1 ml 0.5 ml 5 syringes x 0.1 ml, or 2 syringes x 0.25 ml, or 1 syringe x 0.5 ml 5 syringes x 0.2 ml, or 4 syringes x 0.25 ml, or 2 syringes x 0.5 ml 0.5 ml 2.5 ml 1 ml 5 ml Cancer Type Breast Cancer Melanoma HNSCC of the oral cavity Route of Administration Intradermal, subcutaneous, subareolar, peritumoral Intradermal, subcutaneous Peritumoral Navidea Biopharmaceuticals, Dublin hio, data on file. June

6 Clinical Experience Trial Phase 1 Cancer Type Breast Cancer or Melanoma # Patients Status Primary Endpoint(s) 56 Completed Pharmacokinetics, safety 2 Breast Cancer or Melanoma 80 Completed 2008 Safety and activity (patient localization rate) 3 Study 1 Breast Cancer or Melanoma 179 Completed 2009 Nodal concordance with vital blue dye (VBD) 3 Study 2 Breast Cancer or Melanoma 153 Completed 2011 Nodal concordance/reverse concordance with VBD 3 Head & Neck Squamous Cell Carcinoma 83 snda Approved June, 2014 False negative rate against pathology (removal of all lymph nodes; elective neck dissection ) Navidea Biopharmaceuticals, Dublin hio, data on file. June 2014 Leong SP, et al. Ann Surg ncol. 2011;18(4): Sondak VK, et al. Ann Surg ncol. 2013;20(2): Wallace AM, et al. Ann Surg ncol. 2013;20(8):

7 Phase III Clinical Trials Breast Cancer & Melanoma Conclusions Tc 99m tilmanocept met its pre-specified primary and secondary efficacy endpoints of concordance and reverse concordance in two Phase III Trials in melanoma and breast cancer 99% of blue nodes were also hot and detected by Tc 99m tilmanocept (melanoma p<0.001, breast cancer p<0.0001) (Concordance) Less than two-thirds of the radioactive hot nodes were also blue (Reverse Concordance) Tc 99m tilmanocept identified more lymph nodes in significantly more patients than VBD Tc 99m tilmanocept identified at least one node in 97% of melanoma patients versus 90% with VBD (p=0.002) Tc 99m tilmanocept identified at least one node in 99% of breast cancer patients versus 89% with VBD (p <0.0001) Sondak VK, et al. Ann Surg ncol. 2013;20(2): Wallace AM, et al. Ann Surg ncol. 2013;20(8):

8 Phase III Clinical Trials Breast Cancer & Melanoma Conclusions cont d Lymphoscintigraphy performed in 93% patients: overall, 99% agreement between preoperative lymphoscintigraphy and intraoperative lymphatic mapping Tc 99m tilmanocept detected significantly more disease-containing lymph nodes than VBD 100% of melanoma and 96% (26/27) of breast cancer pathology-positive patients identified VBD exhibited a significantly higher risk of missing disease-containing lymph nodes than Tc 99m tilmanocept (melanoma p=0.004 and breast cancer p=0.03) VBD missed 20% of disease nodes in melanoma, and 24% in breast cancer Tc 99m tilmanocept improved staging accuracy - 9.8% of patients found to have pathology-positive lymph nodes by ILM were upstaged by Tc 99m tilmanocept exclusively; no patients were upstaged by VBD alone In clinical trials, Tc 99m tilmanocept was well tolerated Sondak VK, et al. Ann Surg ncol. 2013;20(2): Wallace AM, et al. Ann Surg ncol. 2013;20(8):

9 Phase III Clinical Trials HNSCC ral Cavity Efficacy Results Summary SLNB with Tc 99m tilmanocept accurately predicts nodal status of HNSCC patients with a false negative rate of 2.56% Intent to Treat Patients (N=83) Diagnostic Performance Metric Value or Rate 95% CI False Negative Subjects (n) 1 True Positive Subjects (n) 38 False Negative Rate* (%), n/n Sensitivity (%), n/n 2.6 (1/39) 97.4 (38/39) (0.06, 13.5) (86.5, 99.9) True Negative Subjects (n) 44 Negative Predictive Value (%), n/n verall Accuracy (%), n/n 97.8 (44/45) 98.8 (82/83) (88.2, 99.9) (93.5, 99.9) *nly one patient had one pathology positive lymph node that was not identified by Tc 99m tilmanocept Navidea Biopharmaceuticals, Dublin hio, data on file. June Agrawal A, Lai S, Civantos F, et al. Results from a prospective phase-3 multi-institutional trial of 99m Tc-tilmanocept, a CD206-targeted molecular sentinel node mapping agent, in head/neck squamous cell carcinoma. Proceedings of the Am Coll Surgeons Annual Clinical Congress. ctober 6-10, Washington, DC. Confidential, Not For Further Dissemination 9

10 Clinical Trials verall Safety Profile in Breast Cancer & Melanoma In clinical trials, 542 patients received Tc 99m tilmanocept No serious hypersensitivity reactions No anaphylactic reactions No serious adverse reactions related to Tc 99m tilmanocept Injection site irritation (3 of 542; 0.6%) and pain (1 of 542; 0.2%) were the most commonly reported adverse reactions ther adverse reactions were uncommon, of mild severity and short duration Since commercialization in May, 2013, the Lymphoseek overall safety profile remains consistent with all prior clinical trial experience Lymphoseek Package Insert. Navidea Biopharmaceuticals. February

11 Phase III Clinical Trials verall Safety Profile in HNSCC ral Cavity 85 patients received Tc 99m tilmanocept and were included in the safety analysis No deaths or serious adverse events were related to Tc 99m tilmanocept 13 serious adverse events (SAEs) in the study None related to Tc 99m tilmanocept 11 of the SAEs were considered related, by investigator, to surgical procedures No adverse events led to discontinuation from the study No reports of injection site pain ne report of mild injection site irritation verall, 36 patients reported at least one AE; mostly mild and not related to Tc 99m tilmanocept Navidea Biopharmaceuticals, Dublin hio, data on file. June 2014 Confidential, Not For Further Dissemination 11

12 Thank You If you have any further questions, contact us for Medical Drug Information Karen Randall, Medical Science Liaison