Life Molecular Imaging GmbH (LMI) announced that florbetaben (18F) has received orphan drug designation from the European Commission for the diagnosis of transthyretin (ATTR) amyloidosis, marking a significant expansion of the radiotracer's diagnostic applications beyond its established use in Alzheimer's disease.
The designation comes as ATTR amyloidosis, while appearing to be the most common form of amyloidosis with rising incidence rates, maintains an overall frequency in the general population below the orphan drug threshold of five cases per ten thousand inhabitants of newly diagnosed patients. The European Medicines Agency (EMA) granted the designation based on this rare disease classification.
Expanding Diagnostic Applications
Florbetaben (18F), marketed as Neuraceq®, was initially developed and approved for detecting neuritic amyloid plaques in the brains of patients with cognitive decline. The radioactive diagnostic agent is currently approved by the FDA, EMA, and MHRA for positron emission tomography (PET) imaging to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment being evaluated for Alzheimer's disease.
Preliminary data suggest that florbetaben (18F) may also detect and quantify ATTR amyloid deposits in the heart and other organs using PET imaging, thereby supporting diagnosis of ATTR amyloidosis. This represents a potential breakthrough in cardiac amyloidosis diagnosis, where accurate identification of disease subtypes is crucial for appropriate treatment selection.
Phase 3 Trial Validation
The efficacy of florbetaben (18F) in diagnosing cardiac amyloidosis is currently being evaluated in an ongoing multi-center Phase 3 study (NCT05184088). The trial aims to further validate the radiotracer's diagnostic capabilities for cardiac amyloidosis, including the ATTR subtype.
"The orphan drug designation for florbetaben (18F) will support our efforts to validate this tracer for the diagnosis of both AL and ATTR cardiac amyloidosis," said Andrew Stephens, MD, PhD, Chief Medical Officer of LMI. "With the approval of several new treatment options, especially for ATTR cardiac amyloidosis, fast and reliable diagnosis of the disease becomes even more important."
Disease Background and Clinical Need
Systemic amyloidosis represents a rare group of complex diseases caused by protein misfolding and subsequent deposition in tissues, resulting in progressive organ damage. ATTR amyloidosis appears to be the most common form of amyloidosis, with incidence rates rising, likely due to prior underdiagnosis of the disease.
Growing awareness of ATTR amyloidosis among cardiologists is improving recognition and diagnosis, allowing patients to access life-saving therapies. Despite the observed rise in prevalence and incidence of cardiac ATTR amyloidosis and its high prevalence among patients with heart failure, the overall frequency in the general population remains below the orphan designation threshold.
Safety Profile
Clinical trial data from 872 subjects with 1,090 florbetaben (18F) administrations, including both demented and non-demented subjects, showed the most frequently observed adverse drug reactions were injection site pain (3.4%), injection/application site erythema (1.7%), and injection site irritation (1.1%).
Dual Orphan Designations
Florbetaben (18F) previously received orphan drug designation as a diagnostic agent for the management of amyloid light chain (AL) amyloidosis in both the European Union and United States. The new ATTR amyloidosis designation expands the radiotracer's potential diagnostic applications across multiple amyloidosis subtypes.
The orphan drug designation provides regulatory incentives and support for developing treatments for rare diseases, potentially accelerating the validation and approval process for florbetaben (18F) in ATTR amyloidosis diagnosis. This development comes at a time when improved diagnostic tools are increasingly important given the availability of new treatment options for ATTR cardiac amyloidosis.
