FDA Grants Fast Track Designation to PI-2620 Tau-PET Diagnostic Scan for Neurodegenerative Diseases

According to a new announcement, the FDA has granted fast track designation to [18F]PI-2620, a tau positron emission tomography (PET) diagnostic, for several neurodegenerative diseases, including Alzheimer disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).^1,2 This designation highlights the significant potential of [18F]PI-2620, developed in collaboration with AC Immune SA and Life Molecular Imaging, to improve diagnosis of these 3 neurodegenerative diseases.

Currently, [18F]PI-2620 is being tested in a phase 3 clinical development program for detecting tau pathology in patients with AD and is also being assessed in other neurodegenerative diseases such as PSP and CBD. Prior research has shown that the compound has had robust brain uptake and fast wash-out in non-target regions, a broad imaging window between 30- and 90-minutes post-injection for AD as well as successful reproducibility between test and retest scans. The absence of significant off-target binding allows PI-2620 to identify and quantify early tau deposition in the brain, which is noted by the companies as a hallmark of neurodegenerative diseases.

“Fast Track Designation for PI-2620 is an important reflection of its potential to accurately diagnose Alzheimer’s and other neurodegenerative diseases. Early diagnosis of these conditions will be key for effective treatment before irreversible damage occurs, and is an essential element in our goal of achieving precision prevention,” Andrea Pfeifer, PhD, CEO at AC Immune SA, commented in a statement.¹ “The FDA has previously granted Fast Track status to two of our active immunotherapies in phase 2 development, ACI-35.030 and ACI-24.060, which target phospho-Tau and Abeta, respectively. The designation for PI-2620 is a further recognition of AC Immune’s drug discovery and development platform and of how we, together with our partners, continue to drive innovation.”

In July 2020, data from a cross-sectional, multicenter study published in JAMA Neurology indicated the value of [18F]PI-2620 to differentiate suspected patients with PSP using PET, potentially facilitating more reliable diagnosis of the disease. In the first comprehensive in vivo evaluation of a tau-PET tracer, postmortem autoradiography showed blockable [18F]PI-2620 binding in patients with PSP and no binding in healthy controls.³

In an attempt to investigate the potential of the novel tau radiotracer [18F]PI-2620 as a biomarker in patients with clinically diagnosed PSP, the researchers recruited 60 patients with PSP, 40 (66.7%) of which had Richardson syndrome (RS; 22 men [55.0%]; mean age, 71 [standard deviation (SD), 6] years; mean PSP rating scale score, 38 [SD, 15]; score range, 13-71) and 20 (33.3%) who had PSP without RS (11 men [55.0%]; mean age, 71 [SD, 9] years; mean PSP rating scale score, 24 [SD, 11]; score range, 11-41).

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Lead author Matthias Brendel, MD, MHBA, department of nuclear medicine, University of Munich, and colleagues then collected 10 healthy controls with disease (2 men; mean age, 67 [SD, 7] years) and 20 controls with disease—10 (50.0%) with Parkinson disease [PD] and multiple system atrophy (MSA; 7 men; mean age, 61 [SD, 8] years) and 10 (50.0%) with AD (5 men; mean age, 69 [SD, 10] years).

The in vivo findings indicated significant elevation of tracer binding in PSP target regions with the strongest differences in PSP versus control groups in the globus pallidus internus (mean distribution volume ratios: PSP-RS, 1.21 [SD, 0.10]; PSP-non-RS, 1.12 [SD, 0.11]; healthy controls, 1.00 [SD, 0.08]; PD/MSA, 1.03 [SD, 0.05]; AD, 1.08 [SD, 0.06]).

Patients with PSP-RS also reported higher binding in the putamen, the substantia nigra, and the dentate nucleus compared with healthy controls, whereas patients with PSP-non-RS did not. Additionally, lower binding indications were observed in the dorsolateral prefrontal cortex and the medial prefrontal cortex in patients with PSP-RS and PSP-non-RS against patients with AD but showed no significant binding differences against a-synucleinopathy patients and healthy cohorts.

At the single-patient level, 34 of 40 individuals (85%) with PSP-RS and 12 of 20 individuals (60%) with PSP-non-RS were classified as PET-positive by the semiquantitative approach, yielding a sensitivity of 85% for PSP-RS and 65% for PSP-non-RS. Researchers observed that 1 of 10 individuals with PD/MSA and 6 of 10 controls with AD were classified as PET-positive in PSP target regions. Ultimately, it led to an overall specificity of 77% in the combined 30 controls by the semiquantitative approach.

Preliminary evidence also showed that the magnitude of [18F]PI-2620 binding in PSP target regions differs between PSP phenotypes, thus pointing to the potential of assessing regional phenotype variability in PSPS by in vivo PET imaging. The highest [18F]PI-2620 binding was observed in PSP-RS followed by PSP with predominant parkinsonism, PSP with predominant frontal presentation, and PSP with predominant corticobasal syndrome.

“Receiving Fast Track Designation from the FDA is a major milestone that highlights the promise of [18F]PI-2620 in addressing the critical need for effective diagnostic tools in Alzheimer’s disease, progressive supranuclear palsy, and corticobasal degeneration,” Andrew Stephens, MD, PhD, chief medical officer at Life Molecular Imaging, said in a statement.² “This designation not only validates our approach but also facilitates closer collaboration with the FDA to expedite the development of [18F]PI-2620. We are committed to advancing this important imaging agent with the potential to make a meaningful difference for patients who need accurate and accessible Tau PET imaging.”

REFERENCES
1. AC Immune’s PI-2620 Tau-PET Diagnostic in Phase 3 Receives Fast Track Designation in Three Neurodegenerative Conditions. News Release. AC Immune SA. News Release. August 28, 2024. Accessed August 28, 2024. https://ir.acimmune.com/news-releases/news-release-details/ac-immunes-pi-2620-tau-pet-diagnostic-phase-3-receives-fast
2. Life Molecular Imaging Receives FDA Fast Track Designation for [18F]PI-2620 in Tau PET Imaging Across Three Neurodegenerative Conditions. News Release. Life Molecular Imaging. August 28, 2024. Accessed August 28, 2024. https://life-mi.com/life-molecular-imaging-receives-fda-fast-track-designation-for-18fpi-2620-in-tau-pet-imaging-across-three-neurodegenerative-conditions/
3. Brendel M, Barthel H, van Eimeren T, et al. Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy [published correction appears in JAMA Neurol. 2020 Nov 1;77(11):1453. doi: 10.1001/jamaneurol.2020.3037]. JAMA Neurol. 2020;77(11):1408-1419. doi:10.1001/jamaneurol.2020.2526