FDA Approves TAUKLARIFY (Florquinitau F 18) PET Tracer for Detecting Tau Pathology in Alzheimer's Disease
核心洞察
The FDA approved TAUKLARIFY (搜索) (florquinitau F 18 (搜索) injection, formerly MK-6240), a PET radiodiagnostic agent for identifying tau neurofibrillary tangle (搜索) pathology in adults with cognitive impairment being evaluated for Alzheimer's disease (搜索).
Two independent clinical studies involving 617 subjects met pre-specified success criteria, with high inter-reader agreement (Fleiss' kappa of 0.92 and 0.86) and favorable safety across 1,734 subjects.
TAUKLARIFY (搜索) received FDA Fast Track designation and enables improved understanding of Alzheimer's disease (搜索) status across the spectrum of cognitive impairment, including early stages.
Enigma Biomedical USA (搜索) (EB USA) announced U.S. Food and Drug Administration (FDA) approval of TAUKLARIFY (搜索) (florquinitau F 18 (搜索) injection, previously referred to as MK-6240), a radiodiagnostic agent indicated for positron emission tomography (PET) of the brain in adults with cognitive impairment who are being evaluated for Alzheimer's disease (搜索) to identify patients with tau neurofibrillary tangle (搜索) (NFT) pathology.
The approval marks a significant milestone in the management of patients being evaluated for Alzheimer's disease (搜索). In 2023, EB USA sold its subsidiary, Cerveau Technologies (搜索), to Lantheus (搜索) to complete development and commercialization of TAUKLARIFY (搜索), and the companies continued to collaborate to advance product development, culminating in this FDA approval.
"TAUKLARIFY (搜索) imaging will enable improved understanding of the status of Alzheimer's disease (搜索) patients across the spectrum of cognitive impairment, including those in the early stages of the disease," said Samantha Budd Haeberlein, PhD, Chief Medical Officer of EB USA. "Two large, independent clinical studies demonstrated the efficacy and safety of TAUKLARIFY in assessing the status of NFTs in patients being evaluated for Alzheimer's disease."
Clinical Study Results
TAUKLARIFY (搜索) was evaluated in two clinical studies. Five independent blinded readers in each study classified scans as positive or negative for tau NFT pathology, and each scan was compared against a pre-established reference standard based on cognitive status and amyloid beta PET pathology status. The studies included scans from a total of 617 subjects, comprising 152 with mild Alzheimer's disease (搜索) dementia, 157 with mild cognitive impairment, and 308 cognitively unimpaired individuals.
Both studies met their pre-specified success criteria. In Study 1 (n=279), reader Positive Percent Agreement (PPA) ranged from 80% (95% CI: 72, 86) to 88% (95% CI: 82, 93), and Negative Percent Agreement (NPA) ranged from 98% (95% CI: 94, 99) to 99% (95% CI: 95, 100). In Study 2 (n=338), reader PPA ranged from 68% (95% CI: 61, 75) to 82% (95% CI: 76, 87), and NPA ranged from 93% (95% CI: 89, 96) to 99% (95% CI: 96, 100).
Inter-reader agreement was high in both studies, with a generalized Fleiss' kappa of 0.92 (95% CI: 0.89 to 0.96) in Study 1 and 0.86 (95% CI: 0.82 to 0.89) in Study 2.
Safety Profile
Safety was evaluated in 1,734 subjects. The most commonly reported adverse reactions, with incidence greater than or equal to 0.1%, were headache (0.7%), nausea (0.2%), injection site reactions (0.1%), dizziness (0.1%), and abdominal discomfort (0.1%).
Indication and Limitations of Use
TAUKLARIFY (搜索) is indicated for PET of the brain in adults with cognitive impairment who are being evaluated for Alzheimer's disease (搜索) to identify patients with tau NFT pathology. The safety and effectiveness of TAUKLARIFY have not been established for the evaluation of non-Alzheimer's disease tauopathies.
The prescribing information includes a warning regarding the risk of misdiagnosis. TAUKLARIFY (搜索) performance for identifying patients with tau NFT pathology was assessed in subjects expected to have predominantly no tau NFT pathology (cognitively unimpaired and amyloid beta PET-negative) or predominantly clinically significant levels of tau NFT pathology associated with Alzheimer's disease (搜索) (cognitively impaired and amyloid beta PET-positive). Performance may be lower in patients in earlier stages of the pathological spectrum. A negative TAUKLARIFY scan does not necessarily exclude the presence of tau NFT pathology, and a positive scan does not necessarily indicate the presence of histopathologically confirmed tau NFT pathology.
TAUKLARIFY (搜索) also contributes to a patient's overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Patients should avoid CYP1A2 inducers, including tobacco smoking, at least 7 days before administration, and lactating women should temporarily discontinue breastfeeding and discard breast milk for a minimum of 4 hours after administration.
Clinical Significance
Rick Hiatt, President and CEO of EB USA, noted that the FDA granted Fast Track designation to TAUKLARIFY (搜索), "a status to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need."
Sterling Johnson, PhD, Jean R. Finley Professor of Geriatrics and Dementia at the University of Wisconsin Alzheimer's Disease (搜索) Research Center, emphasized the tracer's clinical utility: "We have continued to grow our use of TAUKLARIFY (搜索) as our imaging agent of choice for assessment of tau neurofibrillary tangles, based on several clinically important features, particularly its high dynamic range. We find it particularly useful in elucidating the status of AD patients with mild cognitive symptoms."
Alzheimer's disease (搜索) is a degenerative neurological disorder that causes a decline in cognition and function. In the U.S., more than 7 million people are living with Alzheimer's disease, and as the population ages, the number of people 65 and older with the disease may grow to more than 13 million by 2050.