Navidea Biopharmaceuticals, Inc. (NYSE MKT:NAVB), a biopharmaceutical
company focused on precision diagnostic radiopharmaceuticals, today
announced the presentation of additional results from its pivotal Phase
3 clinical trial (NEO3-06) for Lymphoseek® (technetium Tc 99m
tilmanocept) Injection in patients with head and neck squamous cell
carcinoma. Navidea previously announced that the NEO3-06 study met the
primary false negative rate efficacy endpoint of accurately identifying
sentinel lymph nodes (SLNs) in subjects 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.
This surgery is considered the "gold standard" to determine the presence
and extent of cancer spread in lymph nodes of patients with head and
neck squamous cell carcinoma. The now completed full study report
indicates that Lymphoseek also met all other pre-specified study
endpoints, including sensitivity, negative predictive value and overall
accuracy relative to the pathology status of non-SLNs. No differences
were observed in the ability of Lymphoseek to detect SLNs between
same-day or subsequent-day surgery following Lymphoseek injection.
Lymphoseek is a novel, receptor-targeted, small-molecule
radiopharmaceutical approved by the U.S. Food and Drug Administration
for use in lymphatic mapping to assist in the localization of lymph
nodes draining primary tumor in patients with breast cancer or melanoma.
The results were presented at the American College of Surgeons 2013
Annual Clinical Congress by Amit Agrawal, MD, Associate Professor, The
Ohio State University College of Medicine, Department of Otolaryngology
- Head and Neck Surgery, a lead investigator on the NEO3-06 Phase 3
clinical trial.
"Thousands of patients with head and neck cancer stand to benefit from
accurate diagnostic evaluation of their condition, and we are pleased
that the final results for Lymphoseek from our NEO3-06 Phase 3 clinical
trial are being presented to surgeons attending the prestigious American
College of Surgeons Clinical Congress," said Mark Pykett, VMD, PhD,
Chief Executive Officer of Navidea. "The NEO3-06 trial is representative
of Navidea's global strategy to expand Lymphoseek utilization into
multiple cancer types with the aim of assisting physicians in improving
accuracy and evaluating the extent of disease. As previously announced,
we closed the NEO3-06 trial at the recommendation of the Data Safety
Monitoring Committee. Based on study results and data analysis and
dialogue with the U.S. Food and Drug Administration (FDA), we are
working to file an sNDA for Lymphoseek with the FDA by the end of this
year and anticipate EMA action related to the EU MAA for Lymphoseek also
by year end."
"Surgeons who perform lymphatic mapping procedures in patients with head
and neck cancer face unique challenges," commented Dr. Stephen Y. Lai,
MD, PhD, FACS, Associate Professor, Department of Head and Neck Surgery,
The University of Texas MD Anderson Cancer Center and a lead
investigator on the NEO3-06 Phase 3 clinical trial. "Anatomically, we
confront a density of lymph nodes and vessels that are compacted into
small, tight spaces, which can impede the vascular flow of certain
radiolabeled lymphatic mapping agents and hinder our ability to reliably
locate appropriate lymph nodes. We also factor in considerations that
the face and neck are highly sensitive areas and the impact that excess
surgery can have on the patient. The NEO3-06 clinical study is distinct
in comparing the performance of Lymphoseek to the pathological 'gold
standard' of multiple level neck dissection, an extensive procedure in
which a large portion of the head and neck lymph node tissue may be
removed."
"Many surgeons favor removing entire regional lymph node basins because
lymphatic metastases may develop in more than 20% of oral cancer
patients," continued Dr. Lai. "However, excision at this scale may
produce unnecessary morbidity and side effects, leading to
over-treatment for approximately 80% of the patients with
pathology-negative lymph nodes. Receptor-targeted lymphatic mapping
agents like Lymphoseek may facilitate the diagnostic evaluation of these
patients, and help spare them possible morbidity from full regional
lymph node dissections."
"Lymphoseek demonstrated statistically significant results in this
trial, achieving a false negative rate of only 2.56% and nearly 99%
overall accuracy. We believe these results speak to the ability of the
product to identify appropriate tumor-draining lymph nodes," said
Frederick O. Cope, PhD, FACN, Senior Vice President and Chief Scientific
Officer at Navidea. "This next-generation lymphatic mapping agent also
demonstrated key performance metrics in determining sensitivity and
negative predictive value. Importantly, the results also revealed that
there was no difference in Lymphoseek clinical performance between
same-day or subsequent-day surgery following injection of the product,
which may be an important consideration for busy surgeons who often
require flexibility in scheduling lymphatic mapping procedures."
Lymphoseek Data Presented at the American College of Surgeons 2013
Annual Clinical Congress
"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" (NEO3-06 Phase 3
Clinical Trial). The primary endpoint for the NEO3-06 trial was based on
the number of subjects with pathology-positive lymph nodes (lymph nodes
found to harbor cancer) following a multiple level lymph node dissection
and required a minimum of 38 subjects whose lymph nodes contained
pathology-confirmed disease. Of the more than 80 subjects enrolled in
the NEO3-06 trial, 39 subjects were determined to have
pathology-positive lymph nodes. Results demonstrated that Lymphoseek
correctly identified 38 of these 39 patients, for an overall False
Negative Rate (FNR) of 2.56%. This was statistically significant
(p=0.0205) against the statistical threshold for success. These findings
indicate that Lymphoseek accurately identified SLNs in these trial
subjects, and is likely to be predictive of overall node pathology
status. FNR is the rate of occurrence of negative test results in
subjects known to have the disease for which the individual is being
tested. Moreover, multiple level nodal dissection of patients in the
trial with cancer-positive lymph nodes led to an average removal of 38
lymph nodes per patient, whereas Lymphoseek on average led to the
removal of approximately 4 lymph nodes, representing a substantial
reduction in potential morbidity for patients with head and neck cancer
undergoing single lymph node biopsy.
Secondary endpoints for the NEO3-06 trial were the determination of
sensitivity, negative predictive value (NPV) and overall accuracy of
Lymphoseek relative to the pathology status of non-SLNs; and
determination of the detection rate of SLNs by Lymphoseek and rate of
tumor detection in non-SLNs. Lymphoseek demonstrated a sensitivity rate
of 97.6%, an NPV of 97.8% and overall accuracy of 98.8%. No differences
were observed in the ability of Lymphoseek to detect SLNs between
same-day or subsequent-day injection and surgery. The trial also
evaluated safety through observation of adverse events, clinical
laboratory tests, vital signs, electrocardiograms and physical
examinations. There were no deaths associated with the trial. Of 13
serious adverse events, none were determined to be related to Lymphoseek
and no adverse events led to discontinuation from the trial.
"Comparison of false negative rates and overall accuracy of sentinel
lymph node biopsy in Phase 3 99m-Tc-tilomanocept vs. ACOSOG-Z0360
99m-Tc-sulfur colloid in head/neck squamous cell carcinoma."
Francisco J. Civantos, MD, FACS, University of Miami School of Medicine,
Miami, Fla., was lead author on a second presentation that compared
Lymphoseek performance data from the Phase 3 NEO3-06 clinical trial with
published data from the ACOSOG Z-0360 trial, which was conducted using
radiolabeled sulfur colloid. Lymphoseek identified sentinel lymph nodes
(SLNs) in subjects with squamous cell carcinoma of the head or neck
(SCC) with a False Negative Rate (FNR) of 2.56% and sulfur colloid
demonstrated an FNR of 9.8%. Lymphoseek identified SLNs with an overall
accuracy of 99%, whereas the overall accuracy of sulfur colloid was 97%.
There was no difference between SLN procedures performed with Lymphoseek
on the same day as injection versus procedures that were conducted the
following day, more than 15 hours after injection.
About the Lymphoseek Phase 3 Clinical Trial (NEO3-06) in Head and
Neck Cancer
Navidea's Phase 3 clinical trial (NEO3-06) of Lymphoseek was a
prospective, open-label, multicenter, within-patient study of Lymphoseek®
(technetium Tc 99m tilmanocept) Injection. It was designed to identify
sentinel lymph nodes (SLNs) and determine the false negative rate (FNR)
associated with Lymphoseek-identified SLNs relative to the pathological
status of non-SLNs in head and neck and intraoral squamous cell
carcinoma. The NEO3-06 study was a supplement to previously conducted
Phase 3 trials of Lymphoseek in breast cancer and melanoma that were
designed to establish Lymphoseek as an effective radiopharmaceutical
agent for use in lymphatic mapping procedures to identify the lymph
nodes that drain from a primary tumor, which have the highest
probability of harboring cancer. Those studies formed the basis of the
NDA registration package upon which the U.S. Food and Drug
Administration based its approval of Lymphoseek in March, 2013. Navidea
conducted the NEO3-06 clinical study to provide evidence of Lymphoseek
performance in a third cancer type and to potentially enhance and expand
its product label. Navidea previously announced top-line, interim
results from the NEO3-06 trial in April, 2013.
About Lymphoseek®
Lymphoseek® (technetium Tc 99m tilmanocept) Injection is a
novel, receptor-targeted, small-molecule radiopharmaceutical used in
lymphatic mapping procedures that are performed to help in the
diagnostic evaluation of potential cancer spread for patients with
breast cancer and melanoma. Lymphoseek is designed to identify the lymph
nodes that drain from a primary tumor, which have the highest
probability of harboring cancer. Lymphoseek was approved by the U.S.
Food and Drug Administration in March, 2013 for use in lymphatic mapping
to assist in the localization of lymph nodes draining a primary tumor in
patients with breast cancer or melanoma. The Company anticipates
continuing development of Lymphoseek into other solid tumor areas that
may include head and neck cancers, prostate cancer, thyroid cancer,
lung/bronchus cancers, colorectal cancer and others.
Accurate diagnostic evaluation of cancer is critical, as it guides
therapy decisions and determines patient prognosis and risk of
recurrence. According to the American Cancer Society, approximately
232,000 new cases of breast cancer, 77,000 new cases of melanoma and
67,000 new cases of head and neck/oral cancer are expected to be
diagnosed in the United States in 2013.
U.S. Indication and Important Safety Information About Lymphoseek
Indication
Lymphoseek (technetium Tc 99m tilmanocept) Injection is a lymphatic
mapping agent indicated for use with a hand-held gamma counter to assist
in the localization of lymph nodes draining a primary tumor site in
patients with breast cancer or melanoma.
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.
The most common adverse reactions are injection site irritation and/or
pain (<1%).
FULL LYMPHOSEEK PRESCRIBING INFORMATION CAN BE FOUND AT:
WWW.LYMPHOSEEK.COM
About Navidea Biopharmaceuticals, Inc.
Navidea Biopharmaceuticals, Inc. (NYSE MKT:NAVB) is a biopharmaceutical
company focused on the development and commercialization of precision
diagnostics and radiopharmaceutical agents. Navidea is actively
developing four radiopharmaceutical agent platforms - Lymphoseek®,
NAV4694, NAV5001 and RIGScanTM - to help identify the sites
and pathways of undetected disease and enable better diagnostic
accuracy, clinical decision-making and, ultimately, patient care.
Navidea's first commercial agent, Lymphoseek, was approved the U.S. FDA
in March 2013. Navidea's strategy is to deliver superior growth and
shareholder return by bringing to market novel radiopharmaceutical
agents and advancing the Company's pipeline through selective
acquisitions, global partnering and commercialization efforts. For more
information, please visit www.navidea.com.
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including, but not limited to, the Company's continuing operating
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uncertainty of capital funding, dependence on limited product line and
distribution channels, competition, limited marketing and manufacturing
experience, risks of development of new products, regulatory risks and
other risks detailed in the Company's most recent Annual Report on Form
10-K and other Securities and Exchange Commission filings. The Company
undertakes no obligation to publicly update or revise any
forward-looking statements.

Navidea Biopharmaceuticals
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or
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