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Important to 4694:a P3 trial success hit 27% Alzheimer amyloid removal-advance delaydAlso a possible positive signal for Navidea's out licensed 4694 PET imaging ..See April 2013 below Eisai Co Ltd and Biogen Inc significantly slowed cognitive and
functional decline in a large trial of patients in the early stages of
the disease, the companies said on Tuesday.... ....Eisai said the results from the 1,800-patient trial prove the
longstanding theory that removal of sticky deposits of a protein called
amyloid beta from the brains of people with early Alzheimer's can delay
advance of the debilitating disease. Analysts, such as Salim Syed at Mizuho Securities, have said the results would be considered a "win" if lecanemab slowed the rate of decline by around 25%, and that shares of both companies could jump on the news. Lecanemab, like the companies' previous drug Aduhelm, is an antibody designed to remove those amyloid deposits. Unlike Aduhelm, lecanemab targets forms of amyloid that have not yet clumped together. Lecanemab treatment met the primary endpoint and reduced clinical
decline on the global cognitive and functional scale, CDR-SB, compared
with placebo at 18 months by 27%, which represents a treatment
difference in the score change of -0.45 (p=0.00005) in the analysis of
Intent-to-treat (ITT) population. Starting as early as six months,
across all time points, the treatment showed highly statistically
significant changes in CDR-SB from baseline compared to placebo (all
p-values are less than 0.01). All key secondary endpoints were also met
with highly statistically significant results compared with placebo
(p<0.01). Key secondary endpoints were the change from baseline at 18
months compared with placebo of treatment in amyloid levels in the
brain measured by amyloid positron emission tomography (PET), the AD
Assessment Scale-cognitive subscale14 (ADAS-cog14), AD Composite Score
(ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale
for Mild Cognitive Impairment (ADCS MCI-ADL). Navidea Biopharmaceuticals Announces that Results of NAV4694 Clinical Trial Published in the Journal of Nuclear Medicine- Head-to-head comparison of NAV4694 and β-Amyloid imaging gold standard in Alzheimer’s disease and dementia - DUBLIN, Ohio--(BUSINESS WIRE)-- Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB), a biopharmaceutical company focused on precision diagnostic radiopharmaceuticals, today announced the peer-reviewed publication of results from a clinical trial of NAV4694 in healthy subjects and those with diagnosed forms of dementia. The trial assessed the performance of Navidea’s Fluorine-18 labeled amyloid imaging candidate, NAV4694, in a head-to-head comparison with the acknowledged benchmark, gold-standard amyloid imaging agent, 11C-labeled Pittsburgh Compound-B (PiB). Results demonstrated that NAV4694 displayed imaging characteristics nearly identical to those of PiB and the authors believe these results show that NAV4694 may be useful in the early and differential diagnosis of Alzheimer’s disease (AD). The study, “Head-to-Head Comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-Amyloid Imaging in Aging and Dementia,” was published in the current online edition of the Journal of Nuclear Medicine and will appear in the June print edition [J Nucl Med 2013; 54:1–7 DOI: 10.2967/jnumed.112.114785]. β-Amyloid imaging has the potential to play an increasingly important role in clinical practice as revised criteria for the diagnosis of probable AD allow for earlier diagnosis and therapeutic intervention. “For this to be a reality, clinicians will need access to reliable, practical and affordable imaging options,” said Professor Christopher Rowe, MD, FRACP, Director of the Department of Nuclear Medicine and Centre for PET at Austin Health, Melbourne, Australia and one of the authors. ”This study suggests that NAV4694 images may be more easily and reliably read in clinical practice than other F-18 labeled PET tracers. By displaying imaging characteristics nearly identical to those of the gold standard, PiB, NAV4694 provides the same low background needed for earlier differential diagnosis while affording the practicality needed for production logistics.” “With the ongoing movement toward earlier evaluation and treatment of cognitive impairment, it is of increasing importance for an improved diagnostic tool that can identify clinical dementia and cognitive impairment before it has fully developed,” commented Cornelia Reininger, MD, PhD, Navidea’s Senior Vice President and Chief Medical Officer. “These results add to our conviction that NAV4694, with its outstanding performance characteristics, may afford new opportunities to advance the early diagnosis of cognitive decline. We are very excited about the recent initiation of our Phase 2b study evaluating NAV4694 in the differentiation of Mild Cognitively Impaired (MCI) subjects who are at risk of developing Alzheimer’s disease from those who are not, enabling the potential for early intervention with current and future treatments.” About the NAV4694 Head-to-Head Comparison Clinical Trial and Results Forty-five participants (25 healthy elderly controls (HC), 10 with Mild Cognitive Impairment (MCI), 7 with AD and 3 with fronto-temporal dementia) underwent PET imaging with both PiB and NAV4694 imaging agents. The PiB and NAV4694 images were virtually indistinguishable by visual inspection and similarly low to no white matter binding was observed with both radiotracers. Low white matter binding coupled with comparatively high binding to target amyloid provide enhanced signal-to-noise ratios, facilitating detection of lower levels of amyloid. This may enable earlier detection of amyloid and therefore earlier diagnosis of the underlying cause of cognitive impairment and dementia. When quantified, there were no significant differences in white matter binding for each tracer in both healthy controls and dementia subjects. The quantitative measures of NAV4694 binding to cortical amyloid plaques showed almost identical results to PIB. There was an excellent linear correlation between PiB and NAV4694 neocortical standardized uptake value ratios, or SUVR, (slope of 0.95, r = 0.99, P < 0.0001). Both radiotracers showed similar binding kinetics and dynamic range. As expected, the AD group showed higher β-Amyloid detection than the HCs, as measured by both PiB and NAV4694 binding, and provided a robust separation of AD patients from HCs. Of note, the authors state that visually, 16% of the Healthy Controls were deemed positive for β-Amyloid as assessed by both PiB and NAV4694, presenting an almost identical pattern of binding suggesting that β-Amyloid deposition is an early feature of the disease preceding cognitive impairment. No serious adverse events related to the study drugs were observed or reported by any participants as a result of the PiB or NAV4694 scans, and no concerns were raised by the participants or their relatives. Navidea Biopharmaceuticals’ NAV4694 β-Amyloid Imaging Agent to Be Used in Alzheimer’s Disease Studies by Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL)Leading Neurodegenerative Disease and Imaging Research Consortium to Convert to NAV4694 from “Gold Standard” 11C-labeled Pittsburgh Compound-B (PiB) [18F]NAV4694 Imaging to Identify MCI Patients at Risk for Alzheimer's Dementia |
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