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New Drugs Online Report for tilmanocept
Information
Generic Name:
tilmanocept 
Trade Name: Lymphoseek 
Synonym: Tc 99m DTPA mannosyl dextran 
Entry Type: New molecular entity  
 
Developmental Status
UK: Pre-registration (Filed) 
EU: Pre-registration (Filed) 
US: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
March 14: Navidea presented Oral Explanations to the CHMP relating to open questions in the Lymphoseek MAA. At the conclusion of the meeting, the CHMP informed Navidea that the Committee will continue with its review of the MAA. Navidea believes the course of the review continues to be supportive of its market development plans and outlook for material revenue generation in Europe beginning in 2015. [11] 
21/03/2014 09:56:10
Feb 14: FDA has accepted the Supplemental New Drug Application (sNDA) and granted a Priority Review for the expanded use of Lymphoseek® for sentinel lymph node (SLN) detection in patients with head and neck cancer. [10] 
20/02/2014 09:42:53
Mar 13: Approved for marketing in the US for the diagnosis of breast cancer and melanoma [7].  
04/04/2013 19:47:51
Dec 12: Navidea has filed for EU marketing approval for Lymphoseek for use in general Intraoperative Mapping not restricted to any particular solid tumour type [6]. 
27/12/2012 11:04:41
Nov 12: FDA decision on approval expected by 30 Apr 2013 [5]. 
29/11/2012 10:01:36
Nov 12: Company has filed the resubmission for Lymphoseek® in response to the Complete Response Letter received in Sep 2012 [4] 
05/11/2012 09:23:22
Sep 12: The FDA has rejected the application. The company said that the problems were with a third-party contract manufacturer employed to produce Lymphoseek, and not with safety and efficacy data [3]. 
11/09/2012 18:19:14
Oct 11: NDA submitted to FDA in Aug 11 and accepted for review in Oct 11 [1]. 
24/10/2011 13:31:32
 
Trial or other data
Apr 14: In Oct 13 final results from US-based PIII trial of Tc 99m tilmanocept in pts with head and neck squamous cell carcinoma announced (NCT00911326). The primary endpoint (identification of pts with cancerous lymph nodes) was met, as well as all other pre-specified study endpoints. In view of positive top-line results released in April 13, the study´s Data Safety Monitoring Committee recommended closing the study early; the company formally closed the trial in Aug 13. [12] 
02/04/2014 11:24:25
Mar 13: Top-line results from the interim analysis of PIII trial NEO3-06 demonstrated that Lymphoseek met the primary efficacy endpoint of accurately identifying sentinel lymph nodes (SLNs) in pts with squamous cell carcinoma of the head or in the mouth, as compared to the removal of all lymph nodes during multiple level nodal dissection surgery of the head and neck. Of the over 80 pts enrolled in the NEO3-06 trial, 39 pts were determined to have pathology-positive lymph nodes. Results demonstrated that of these 39 pts, Lymphoseek accurately identified 38, for an overall False Negative Rate (FNR) of 2.56%, which was statistically significant (p=0.0205) and met the statistical threshold for success of the primary endpoint [9].  
05/04/2013 08:35:00
Mar 13: The study, “Comparative Evaluation of [99mTc] Tilmanocept for Sentinel Lymph Node Mapping in Breast Cancer Patients: Results of Two PIII Trials,” was published in the current online edition of the journal Annals of Surgical Oncology [DOI 10.1245/s10434-013-2887-8] [8] 
25/03/2013 17:00:39
Oct 12: “Combined Analysis of Phase III Trials Evaluating [99mTc]Tilmanocept and Vital Blue Dye for Identification of Sentinel Lymph Nodes in Clinically Node-Negative Cutaneous Melanoma,” published early online in Annals of Surgical Oncology [DOI 10.1245/s10434-012-2612-z].  
11/10/2012 08:52:18
Jun 12: Abstract of a meta-analysisof PIII trials for Intraoperative lymphatic mapping (ILM) of lymph nodes in breast cancer, compared to standard of care techniques has been published in conjunction with ASCO in the Journal of Clinical Oncology Online 2012; e21066; The novel receptor targeted (CD206) 99mTc-labeled tilmanocept versus the currently employed Tc99m-sulfur colloid in intraoperative lymphatic mapping (ILM) on key performance metrics in breast cancer” [2]. 
06/06/2012 13:54:48
Lymphoseek has undergone study in two prospective open-label non-randomised PIII studies (NEO3-05 and NEO3-09; NCT01106040 and NCT00671918) in >300 patients with either breast cancer or melanoma. The primary was the concordance on a lymph node count basis of Lymphoseek with vital blue dye. Lymphoseek met all primary and secondary endpoints across both studies [1]. 
24/10/2011 13:31:52
Used in Intraoperative Lymphatic Mapping (ILM). ILM with a radiopharmaceutical identifies the first lymph node to receive lymphatic flow from the primary tumour site. The node is removed and analyzed for the presence of malignant cells. By locating the lymph node prior to surgery, a smaller incision and lymph node dissection can be employed. Lymphoseek is a radiotracer that accumulates in lymphatic tissue by binding to a mannose binding protein that resides on the surface of dendritic cells and macrophages. It has a diameter of about 5 nm, which is smaller than current agents used for targeting lymphoid tissue. This permits enhanced diffusion into lymph nodes and blood capillaries, resulting in a rapid injection site clearance.  
24/10/2011 13:31:43
 
Evidence Based Evaluations
NHSC/NIHR  http://www.hsc.nihr.ac.uk/topics/lymphoseek-for-lymphatic-mapping-and-sentinel/ 
   
References  
Available only to registered users
Category
BNF Category:
Awaiting Update (99)
Pharmacology: Radionuclide imaging enhancers  
Epidemiology:  
Indication: Cancer 
Additional Details: diagnosis of solid tumours 
 
Company Information
Name: Navidea  
US Name: Neoprobe Corporation 
 
NICE Information
In timetable: No  
When: