A novel diagnostic agent to identify patients with tau neurofibrillary tangles (NFTs), including NFTs isolated to the medial temporal lobe
KNOXVILLE, Tenn.–(BUSINESS WIRE)–Enigma Biomedical USA (EB USA) today announced the U.S. Food and Drug Administration (FDA) approval of TAUKLARIFY™ (florquinitau F 18 injection, also 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 to identify patients with tau neurofibrillary tangle (NFT) pathology.
In 2023, EB USA sold its subsidiary, Cerveau Technologies, to Lantheus to complete development of and commercialization of TAUKLARIFY. The companies have continued to collaborate to advance product development, which has culminated in this FDA Approval.
Rick Hiatt, President and CEO of EB USA stated: “The FDA granted Fast Track designation to TAUKLARIFY, a status to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. With the approval of TAUKLARIFY, EB USA demonstrates its ongoing commitment to be the premier developer of imaging biomarkers for neurological pathologies to accelerate the development, approval, and adoption of effective therapies to treat neurodegenerative diseases.”
“TAUKLARIFY imaging will enable improved understanding of the status of Alzheimer’s disease 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. As Alzheimer’s research moves towards an increased focus on early disease detection and treatment, TAUKLARIFY is uniquely suited to address those emerging needs.”
“This approval is an important and critical step forward in the management of patients being evaluated for Alzheimer’s disease,” said Sterling Johnson, PhD, Jean R. Finley Professor of Geriatrics and Dementia, Associate Director and Core Leader of the Wisconsin Alzheimer’s disease Research Center, and Associate Director of the Wisconsin Alzheimer’s institute. “The University of Wisconsin Alzheimer’s disease Research Center is proud to have been one the earliest adopters of MK-6240 in the academic research setting. We have continued to grow our use of TAUKLARIFY 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. We are excited to witness the transition of this valuable tool from research to broad community clinical use enabled by this approval.”
TAUKLARIFY was evaluated in two clinical studies. Five independent blinded readers in each study classified scans as positive or negative for tau neurofibrillary tangle (NFT) pathology and each scan was then 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, including 152 with mild Alzheimer’s disease dementia, 157 with mild cognitive impairment, and 308 cognitively unimpaired individuals. Both studies met their pre-specified success criteria:
– Study 1, (n=279), with reader Positive Percent Agreement* (PPA) (95% CI) ranging from 80% (72, 86) to 88% (82, 93), and Negative Percent Agreement (NPA) from 98% (94, 99) to 99% (95, 100).
– Study 2, (n=338), with reader PPA (95% CI) ranging from 68% (61, 75) to 82% (76, 87), and NPA from 93% (89, 96) to 99% (96, 100).
Inter-reader agreement was high in both studies, with a generalized Fleiss’ kappa of 0.92 in Study 1, and 0.86 in Study 2. Safety was evaluated in 1,734 subjects. The most commonly reported adverse reactions were headache (0.7%), nausea (0.2%), injection site reactions (0.1%), dizziness (0.1%), and abdominal discomfort (0.1%)1.
TAUKLARIFY™ Indication
TAUKLARIFY is indicated for positron emission tomography (PET) of the brain in adults with cognitive impairment who are being evaluated for Alzheimer’s disease to identify patients with tau neurofibrillary tangle (NFT) pathology.
TAUKLARIFY Limitations of Use
The safety and effectiveness of TAUKLARIFY have not been established for the evaluation of non-Alzheimer’s disease tauopathies.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Risk of Misdiagnosis in Patients Being Evaluated for Alzheimer’s Disease
TAUKLARIFY performance for identifying patients with tau NFT pathology was assessed in subjects who were expected to have predominantly no tau NFT pathology (i.e., cognitively unimpaired and amyloid beta PET-negative) or predominantly clinically significant levels of tau NFT pathology associated with Alzheimer’s disease (i.e., cognitively impaired and amyloid beta PET-positive). TAUKLARIFY performance for identifying patients with tau NFT pathology 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 TAUKLARIFY scan does not necessarily indicate the presence of histopathologically confirmed tau NFT pathology. Consider additional evaluation when clinical uncertainty remains.
Radiation Risk
TAUKLARIFY contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe drug handling to protect patients and health care providers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.
Adverse Reactions
The most commonly reported adverse reactions, with incidence greater than or equal to 0.1%, were headache, discomfort, nausea, injection site reactions and dizziness.
Drug Interactions
CYP1A2 inducers: Avoid use of CYP1A2 inducers, including tobacco smoking, at least 7 days before TAUKLARIFY administration.
Use in Specific Populations
Lactation: Temporarily discontinue breastfeeding. A lactating woman should pump and discard breast milk for a minimum of 4 hours after TAUKLARIFY administration.
To report SUSPECTED ADVERSE REACTIONS, contact Cerveau, a Lantheus company, at 1-800-362-2668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information for TAUKLARIFY.
https://www.lantheus.com/tauklarify-prescribing-information
About Enigma Biomedical – USA
Enigma Biomedical USA’s vision is to be the premier provider of imaging biomarkers for neurological pathologies, associated information technology, and related tools to accelerate the development, approval, and adoption of effective therapies to treat neurodegenerative diseases. EB USA’s neuroimaging biomarkers provide pharma and academic researchers with state-of-the-art tools for enabling disease-targeted therapy development with the highest precision and accuracy. In pursuit of this vision, subsidiaries of EB USA have provided the best-in-class tau and amyloid PET imaging biomarkers, MK-6240, now TAUKLARIFY, and NAV-4694, to our academic and pharmaceutical partners to enable their research efforts. Both tracers were acquired by Lantheus for further development. EB USA also recently announced a partnerships with AbbVie and the Concussion Legacy Foundation/Boston University Chronic Traumatic Encephalopathy (CTE) Center to explore their novel 4R Tau PET Imaging Biomarkers, Alamar Biosciences and Pharmalogic. Additionally, EB USA was awarded a $2 million grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) for the discovery and initial preclinical development of a novel α-synuclein PET Imaging biomarker.
*_PPA (Positive Percent Agreement) represents the percentage of patients with a positive TAUKLARIFY PET result among those who were tau reference standard positive. NPA (Negative Percent Agreement) represents the percentage of patients with a negative TAUKLARIFY PET result among those who were tau reference standard negative.
Contacts
Enigma Biomedical Group President and CEO
[email protected]