CLINICAL TRIALS PROFILE FOR TECHNETIUM TC-99M TILMANOCEPT

All Clinical Trials for technetium tc-99m tilmanocept

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02589366 ↗	Lymphoseek as Lymphoid Tissue Targeting Agent in Patients With Cancer of the Endometrium	Terminated	Cardinal Health 414, LLC	Phase 1	2015-11-01	Part of standard treatment for endometrial cancer is to remove one or more groups of lymph nodes (lymph node dissection). Lymph nodes are small, bean-shaped organs located within the body throughout the lymphatic system (the tissues and organs involved in immunity, which aids in the fight against infection and cancer). The purpose of this study is to compare the safety and ability of Lymphoseek and a Vital Blue Dye (tracing agent) to find lymph nodes that may carry cancer from the tumor through the lymphatic system. Lymphoseek will be injected into the tumor on the day before surgery to remove lymph nodes. Vital Blue Dye will be administered during surgery to trace the cancer as well. The surgeon will remove the lymph nodes as part of routine surgery and will keep track of which lymph nodes are identified by Lymphoseek and Vital Blue Dye. These nodes will be sent to another doctor to view them under a microscope and see if the nodes contain cancer cells. The hypothesis is that Lymphoseek can be used safely and will be at least as effective as blue dye in identifying the lymph nodes that may have cancer cells.
NCT02201420 ↗	Evaluation of Tc 99m Tilmanocept Localization in Primary Cutaneous Kaposi's Sarcoma and Lymphatic Drainage by SPECT/CT	Completed	Navidea Biopharmaceuticals	Phase 2	2014-09-01	The purpose of this study (NAV3-12) is to determine the dissemination and localization of Tc 99m tilmanocept by SPECT and SPECT/CT imaging in subjects with confirmed cutaneous KS. This is a single center, open-label, within-subject study.
NCT02065232 ↗	Sentinel Lymph Node Mapping Post-Injection Site Pain	Completed	Navidea Biopharmaceuticals		2014-03-01	This is a pain survey study that will compare the level of discomfort experienced by breast cancer patients after injection of either technetium-labeled sulfur colloid or technetium-labeled tilmanocept, both FDA-approved agents used for sentinel lymph node biopsy (SLNB). Breast cancer patients who are already scheduled for SLNB as part of their original surgical plan will be asked to participate in this study and be randomized to receive either technetium-labeled sulfur colloid or technetium-labeled tilmanocept. After injection, patients will complete pain questionnaires to measure the amount of discomfort they are feeling during and after they receive the injection. There will be no change to the patient's treatment plan other than the addition of pain questionnaires. The investigators' hypothesis is that patients will feel less discomfort after injection of tilmanocept versus sulfur colloid.
NCT02065232 ↗	Sentinel Lymph Node Mapping Post-Injection Site Pain	Completed	University of California, San Diego		2014-03-01	This is a pain survey study that will compare the level of discomfort experienced by breast cancer patients after injection of either technetium-labeled sulfur colloid or technetium-labeled tilmanocept, both FDA-approved agents used for sentinel lymph node biopsy (SLNB). Breast cancer patients who are already scheduled for SLNB as part of their original surgical plan will be asked to participate in this study and be randomized to receive either technetium-labeled sulfur colloid or technetium-labeled tilmanocept. After injection, patients will complete pain questionnaires to measure the amount of discomfort they are feeling during and after they receive the injection. There will be no change to the patient's treatment plan other than the addition of pain questionnaires. The investigators' hypothesis is that patients will feel less discomfort after injection of tilmanocept versus sulfur colloid.
NCT01902953 ↗	Lymphoseek® as Lymphoid Tissue Targeting Agents in Colon Cancer(CNC)	Completed	Maimonides Medical Center	Phase 2	2013-03-01	45 patients undergoing a colon (large bowel/intestine)removal operation for the diagnosis of colon cancer will be included in this study. During colon operation the affected portion of the colon is removed. In addition, lymph nodes are included in the specimen and evaluated by a pathologist. Analysis of the lymph nodes in the specimen are important because this is an important aspect of determining the stage of the cancer. Once the standard technique is used for the colon removal operation and the specimen is removed it will be injected with two drugs to help identify the lymph nodes. One is a blue dye and the other a radiotracer. The colon and ALL of the lymph nodes will then be sent for the standard pathologic evaluation. The patient themselves will never be injected with these drugs being used for research. Following the standard lymph node evaluation, an additional pathologist at an outside research facility will further examine the lymph nodes in the specimen using more in depth techniques which are above and beyond the standard of care. The results of all the pathologic tests will be conveyed to the surgeon of record to help in their decision making regarding further treatment. The study hypothesis is that radiotracer will be at least as effective as blue dye in identifying the lymph nodes most likely to harbor cancer cells (sentinel nodes). Once identified, these sentinel nodes can then undergo a more in depth review leading to improved staging of colorectal cancer and more accurate treatment.

Clinical Trial Conditions for technetium tc-99m tilmanocept

Condition Name

Condition Name for technetium tc-99m tilmanocept
Intervention	Trials
Head and Neck Squamous Cell Carcinoma	1
Kaposi's Sarcoma	1
Liver Metastases	1
Melanoma	1

Condition MeSH

Condition MeSH for technetium tc-99m tilmanocept
Intervention	Trials
Neoplasm Metastasis	1
Sarcoma	1
Liver Neoplasms	1
Melanoma	1

Clinical Trial Locations for technetium tc-99m tilmanocept

Trials by Country

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−

Trials by Country for technetium tc-99m tilmanocept
Location	Trials
United States	6
Switzerland	1

Trials by US State

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−

Trials by US State for technetium tc-99m tilmanocept
Location	Trials
California	4
Alabama	1
New York	1

Clinical Trial Progress for technetium tc-99m tilmanocept

Clinical Trial Phase

Clinical Trial Phase for technetium tc-99m tilmanocept
Clinical Trial Phase	Trials
Phase 2	3
Phase 1	2
Early Phase 1	1

Clinical Trial Status

Clinical Trial Status for technetium tc-99m tilmanocept
Clinical Trial Phase	Trials
Completed	3
Terminated	2
Suspended	1

Clinical Trial Sponsors for technetium tc-99m tilmanocept

Sponsor Name

Sponsor Name for technetium tc-99m tilmanocept
Sponsor	Trials
Navidea Biopharmaceuticals	4
University of California, San Diego	2
National Cancer Institute (NCI)	2

Sponsor Type

Sponsor Type for technetium tc-99m tilmanocept
Sponsor	Trials
Other	5
Industry	5
NIH	3

Technetium Tc-99m Tilmanocept: Clinical Trials Update, Market Analysis, and Projections

Introduction

Technetium Tc-99m tilmanocept, known by the brand names Lymphoseek, Lymphoaim, and others, is a radiopharmaceutical diagnostic imaging agent that has been approved by the U.S. Food and Drug Administration (FDA) for lymphatic mapping and guiding sentinel lymph node biopsy. Here, we will delve into the recent clinical trials, market analysis, and projections for this drug.

Clinical Indications and Mechanism of Action

Technetium Tc-99m tilmanocept is designed to selectively target the CD206 receptors on the surface of macrophages and dendritic cells in lymph nodes. This selective binding allows for accurate detection of sentinel lymph nodes (SLNs) in various cancers, including breast cancer, melanoma, and squamous cell carcinoma of the oral cavity[1].

Recent Clinical Trials

Lymphatic Mapping and Sentinel Lymph Node Biopsy

Clinical studies have consistently shown that technetium Tc-99m tilmanocept is highly effective in detecting SLNs. For instance, a study in the Australian setting demonstrated a 100% sensitivity and intraoperative retrieval rate of SLNs, with no false positives[5].

Rheumatoid Arthritis (RA) Trials

Navidea Biopharmaceuticals has been conducting clinical trials to evaluate the use of technetium Tc-99m tilmanocept for predicting treatment response in patients with rheumatoid arthritis (RA).

• Phase 2B and Phase 3 Trials: These trials aimed to assess whether technetium Tc-99m tilmanocept imaging could serve as an early predictor of treatment response in RA patients switching to anti-TNFα therapy. While the imaging successfully targeted and produced reliable images of macrophage activity, the results did not meet the expected predictive accuracy for treatment response, with an overall accuracy below 70%[3][4].

Market Analysis

Current Market Value and Projections

The market potential for technetium Tc-99m tilmanocept is significant, particularly in the context of RA treatment.

• U.S. and EU Market Valuation: A third-party valuation report by LifeSci Consulting estimated that peak combined U.S. and EU sales could reach $1.2 billion annually under base-case assumptions, and up to $2.6 billion in an upside scenario. This valuation is based on the need for a tool to predict treatment response in RA patients and potential expansion into other therapeutic areas[2].

Market Needs and Opportunities

Rheumatologists have highlighted the need for a noninvasive, quantifiable method to predict treatment response early in RA therapy. Despite the recent trial results, there is still a large unmet medical need in this area. Opportunities for added value include expanding indications to other classes of RA therapeutics and registering technetium Tc-99m tilmanocept as a biomarker for activated macrophages in RA patients[2].

Challenges and Future Directions

Clinical Trial Outcomes

The recent exploratory analysis from the NAV3-33 clinical trial showed that while technetium Tc-99m tilmanocept can target and image macrophage activity in RA patients, it did not adequately predict treatment response. This outcome has raised questions about the commercial viability of the product in this specific indication[3].

Optimizing Diagnostic Performance

To overcome the current limitations, Navidea Biopharmaceuticals is focusing on optimizing the diagnostic performance of technetium Tc-99m tilmanocept. This includes refining methodologies and potentially exploring other therapeutic areas where the drug's unique properties could offer significant benefits[3][4].

Market Projections and Growth Potential

Established Indications

In its established indications for lymphatic mapping and SLN biopsy, technetium Tc-99m tilmanocept has demonstrated high accuracy and reliability. This solid foundation is expected to continue driving sales in these areas.

Emerging Indications

Despite the setbacks in the RA trials, the drug's potential in other emerging indications, such as predicting treatment response in different diseases or as a biomarker, remains promising. The ability to target and image macrophage activity could open up new avenues for diagnostic and therapeutic applications[2][3].

Key Takeaways

• High Accuracy in Lymphatic Mapping: Technetium Tc-99m tilmanocept has shown excellent performance in detecting SLNs in various cancers.
• RA Trials: Recent trials for predicting treatment response in RA patients did not meet expected predictive accuracy, but the drug still holds potential in other therapeutic areas.
• Market Potential: Significant market value is projected, especially if the drug can be successfully applied to other indications or as a biomarker.
• Future Directions: Optimizing diagnostic performance and exploring new therapeutic areas are key to unlocking the full potential of technetium Tc-99m tilmanocept.

FAQs

Q: What is technetium Tc-99m tilmanocept used for?

A: Technetium Tc-99m tilmanocept is used for lymphatic mapping and guiding sentinel lymph node biopsy in various cancers, and it is being explored for predicting treatment response in rheumatoid arthritis.

Q: How does technetium Tc-99m tilmanocept work?

A: It selectively binds to CD206 receptors on the surface of macrophages and dendritic cells in lymph nodes, allowing for accurate detection of sentinel lymph nodes.

Q: What were the results of the recent RA trials?

A: The trials showed that technetium Tc-99m tilmanocept could target and image macrophage activity but did not adequately predict treatment response in RA patients.

Q: What is the market potential for technetium Tc-99m tilmanocept?

A: The market potential is significant, with projected peak sales of up to $2.6 billion annually in the U.S. and EU markets under certain assumptions.

Q: What are the future directions for technetium Tc-99m tilmanocept?

A: Future directions include optimizing diagnostic performance, exploring new therapeutic areas, and potentially registering the drug as a biomarker for activated macrophages.

Sources

1. DrugBank: Technetium Tc-99m tilmanocept - DrugBank.
2. Navidea Biopharmaceuticals: Navidea Biopharmaceuticals Announces Updated Third-Party Valuation Report for Tc99m Tilmanocept.
3. Navidea Biopharmaceuticals: Navidea Biopharmaceuticals, Inc. Announces Results of Exploratory Analysis of NAV3-33 Clinical Trial.
4. CenterWatch: Tc 99m Tilmanocept Imaging for Early Prediction of Anti-TNFα Therapy Response in Moderate to Severe Active RA.
5. Navidea Biopharmaceuticals: Navidea Biopharmaceuticals Announces Publication of Study Evaluating Tc99m Tilmanocept in Australian Setting.