FDA Grants Fast Track Designation to PET Tau Tracer APN1607 for Progressive Supranuclear Palsy

Brad Navia, MD

According to a new announcement, the FDA has granted fast track designation to Aprinoia’s APN-1607, a first-in-class radioactive diagnostic PET imaging tracer of tau aggregates, for patients with suspected progressive supranuclear palsy (PSP). APN-1607 is currently being tested in a global phase 3 trial to evaluate its performance as a biomarker for the early diagnosis of PSP.¹

Currently, there are no FDA-approved diagnostic markers for PSP or any other rare tau-related disorders such as frontotemporal dementia. APN-1607, a radioactive fluorinated molecule developed to visualize and quantify 3R and 4R tau aggregates by PET imaging, has already previously received orphan drug designation and has been clinically utilized in over 3000 patients through investigator-initiated and sponsor trials.

With the fast track designation, the belief is that this will help facilitate the development and expedite the review of product candidates like APN-1607 to help address unmet medical need. If the results from the anticipated phase 3 trial are positive, they will serve as the primary basis of approval of APN-1607 in the United States.

"We are very pleased with the FDA’s decision to grant APN-1607 Fast Track Designation as it underscores the significant unmet medical need for a diagnostic marker for the early diagnosis of PSP and potentially other tau-related disorders, including Alzheimer’s disease,” Brad Navia, MD, chief medical officer at Aprinoia, said in a statement.¹ "APN1607 is a unique imaging agent as it was designed to detect specific forms of tau implicated in PSP and other related disorders. Sadly, patients with PSP can remain undiagnosed for several years as it is often confused with other Parkinson’s like disorders, especially during the early stages."

He added, "If approved, APN-1607 would provide physicians with an important diagnostic tool that will allow them to diagnose PSP with greater confidence and differentiate it from other disorders, thereby improving the management of these patients."

In December 2023, Aprinoia received a “Study May Proceed” letter from the FDA to conduct a large-scale, multicenter, open-label study to evaluate the efficacy and safety of APN-1607 as a diagnostic marker in patients suspected to have PSP. The global trial is expected to include sites in the United States, Europe, the United Kingdom, and Asia.²

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During the same month, the company completed enrollment for a phase 3 study (NCT05542953) to evaluate the efficacy and safety of APN-1607 for the diagnosis of Alzheimer disease (AD). According to clinicaltrials.gov, the trial has an estimated enrollment of 230 participants, aged 50 to 85 years old, who are either healthy or have a diagnosis of mild cognitive impairment or AD. The trial uses regional uptake patterns of APN-1607 assessed in regions of interest that are relevant to AD pathology as the primary outcome, with safety and adverse events (AEs) as the secondary outcome measure.

"Providing patients with neurodegenerative disorders, such as Alzheimer’s, and PSP with an early and accurate diagnosis is critical for determining the best course of treatment as well as accelerating drug development via clinical trials. The Fast-Track Designation for Aprinoia’s PET tracer is a milestone for the field that will serve as the first tau imaging agent for PSP and will add to the arsenal of tau imaging tools for Alzheimer disease," Howard Fillit, MD, PhD, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said in a statement.¹ "This new generation PET Tracer – in addition to other biomarkers – will move us closer to the day when we can treat the right patients with the right drugs at the right time through a precision medicine approach."

In 2021, a study published in Movement Disorders investigated the clinical utility of APN-1607 in the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP. The trial enrolled 3 groups consisting of patients with PSP (n = 20), patients with a-synucleinopathies (multiple system atrophy with predominant parkinsonism: n = 7; PD: n = 10), and age- and sex-matched health controls (n = 13).³

Compared with healthy controls, patients with PSP showed increased 18F-APN-1607 binding in several subcortical regions, including the striatum, putamen, globus pallidus, thalamus, subthalamic nucleus, midbrain, tegmentum, substantia nigra, pontine base, red nucleus, raphe nuclei, and locus coeruleus. In addition, the severity of PSP was positively correlated with the amount of 18F-APN-1607 uptake in the subthalamic nucleus, midbrain, substantia nigra, red nucleus, pontine base, and raphe nuclei.

REFERENCES
1. APRINOIA Therapeutics Announces Fast Track Designation Granted by U.S. FDA to APN-1607 (florzolotau) for the Diagnosis of Progressive Supranuclear Palsy. News release. Aprinoia Therapeutics. May 20, 2024. Accessed May 20, 2024. https://finance.yahoo.com/news/aprinoia-therapeutics-announces-fast-track-120000291.html
2. Aprinoia Therapeutics Inc. receives “Study May Proceed” letter from FDA for a phase 3 study of APN-1607 (Florzolotau) for the diagnosis of progressive supranuclear palsy. News release. January 3, 2024. Accessed May 20, 2024. https://aprinoia.com/aprinoia-therapeutics-inc-receives-study-may-proceed-letter-from-fda-for-a-phase-3-study-of-apn-1607-florzolotau-for-the-diagnosis-of-progressive-supranuclear-palsy/
3. Li L, Liu FT, Li M, et al. Clinical utility of 18F-APN-1607 tau PET imaging in patients with progressive supranuclear palsy. Mov Disord. 2021;36(10):2314-2323. doi:10.1002/mds.28672