Navidea Biopharmaceuticals, Inc., a biopharmaceutical company focused on precision diagnostic radiopharmaceuticals, has reported results of its investigational beta-amyloid imaging agent, NAV4694, which produced highly differentiated images in the first cohort of subjects enrolled in the its phase IIb positron emission tomography (PET) imaging study of subjects with Mild Cognitive Impairment (MCI). The subjects were enrolled and evaluated at the Alzheimer's Disease Centre at Quincy Medical Centre, Quincy, Massachusetts. The results indicate that NAV4694 produced high-quality diagnostic images that segregated MCI subjects into two discrete groups, either amyloid-positive or amyloid-negative.

The image evaluation was performed on twelve subjects meeting pre-defined inclusion/exclusion criteria for emerging, or early-stage, cognitive impairment. NAV4694 scans were assessed by two independent readers using a 3-point visual scale. Image interpretation used the Company’s proprietary visual-read algorithm. All twelve MCI subjects segregated into either amyloid-positive or amyloid-negative categories. The technical quality of the scans was good and both raters were in complete agreement on the 3-point scale, with eight scans highly positive for ß-amyloid and four scans negative. There were no intermediate ratings or ambiguous cases despite the early-stage characterization of the subjects’ cognitive impairment status. The scans were easy to read and the readers noted that the high gray matter relative to white matter signal made image interpretation very straight forward. To date, the product candidate appears to be safe and well-tolerated. Results are expected to be presented at an upcoming scientific conference on Alzheimer’s disease (AD).

“We are very pleased with the diagnostic image quality of NAV4694 in patients with mild cognitive impairment, offering the potential to identify individuals who are at high risk of developing dementia caused by AD before their symptoms become severe,” said Dr Anil K Nair, MD, chief of Neurology and head of the Alzheimer's Disease Centre at Quincy Medical Centre. “These patients are routinely the most difficult to diagnose. The images generated using NAV4694 are easy to interpret and have resulted in the segregation of early-stage patients into two discrete categories: those with positive scans versus those with negative scans. We are encouraged at the potential to separate patients with emerging disease, enabling earlier and more accurate differentiation of MCI subjects who are at risk of developing AD from those who are not and before the disease has advanced to the stage of impairing daily activities. If AD could be diagnosed at an earlier stage, before clinical dementia has fully developed, the potential for successful intervention with current and future treatments could be improved considerably.”

“We are very pleased with the performance of NAV4694 in this initial MCI cohort and with the progress of the phase IIb trial in general,” commented Cornelia Reininger, MD, PhD, Navidea’s senior vice president and chief medical officer. “Results to date across all phase II studies indicate the efficacy of NAV4694 in detecting beta-amyloid while exhibiting low white-matter uptake for clearer images, which may be one reason for the promising results obtained in this initial assessment of subjects with MCI.”

Dr Reininger continued, “As the dementia field moves to earlier evaluation and treatment of cognitive impairment, it is of increasing importance to have diagnostic agents that can accurately detect the underlying cause. Our ultimate goal is to provide an improved diagnostic tool with outstanding performance characteristics for physicians to aid in the diagnosis of Alzheimer's disease and other forms of neurodegenerative dementia.”

NAV4-04 is a phase IIb, open-label, multiple-centre, non-randomized, PET imaging study to assess the safety and efficacy of NAV4694 in subjects diagnosed with MCI to investigate whether NAV4694 has the ability to detect beta-amyloid in PET scans in subjects with MCI. Enrollment is ongoing and is expected to accelerate in conjunction with the expanded availability of the NAV4694 tracer following the recent completion of technical transfer activities at PET manufacturing facilities.

NAV4694 is an investigational Fluorine-18 labeled precision radiopharmaceutical candidate intended for use in Positron Emission Tomography (PET) imaging and evaluation of patients with signs or symptoms of cognitive impairment such as AD. NAV4694 binds to beta-amyloid deposits in the brain that can then be imaged in scans. Beta-amyloid plaque pathology is widely used in the diagnosis of AD. The ability of NAV4694 imaging to display amyloid plaque pathology may enable earlier identification of AD and improve monitoring of disease progression and interpretation of brain scan images. Navidea’s phase III programme for NAV4694 in AD is also underway.