What Is 124I-evuzamitide?
124I-evuzamitide is an investigational imaging agent designed to help visualize amyloid deposits in the body. It is an iodine-124 (124I) labeled 45 L-amino acid peptide, also known as p5+14. This peptide works by binding to various forms of amyloid through multivalent electrostatic interactions with the amyloid fibril itself and with associated heparan sulfate proteoglycans.
Once administered, 124I-evuzamitide allows for PET/CT imaging to evaluate where amyloid has accumulated, particularly in the heart. Participants in studies typically receive a single intravenous injection of approximately 1 mCi (±10%) of the agent. Imaging is then performed a few hours later to assess myocardial uptake.
Currently, 124I-evuzamitide is under study for its potential use in identifying amyloid deposits associated with conditions such as Cardiac Amyloidosis, Amyloidogenic Transthyretin (ATTR) Amyloidosis, and Transthyretin Amyloidosis.
Uses and Conditions Under Study
124I-evuzamitide is being investigated as an imaging agent to detect and visualize amyloid deposits in various conditions. Amyloidosis is a group of diseases characterized by the abnormal buildup of amyloid proteins in organs and tissues, which can impair their function.
The drug is currently being studied in clinical trials for several amyloid-related conditions:
- Cardiac Amyloidosis: This condition involves amyloid deposits in the heart, which can lead to heart failure. Three trials are investigating 124I-evuzamitide's ability to image these deposits.
- Amyloidogenic Transthyretin (ATTR) Amyloidosis and Transthyretin Amyloidosis: These are forms of amyloidosis where the transthyretin protein misfolds and forms amyloid fibrils. One trial is studying 124I-evuzamitide for each of these conditions, aiming to visualize the extent of amyloid accumulation.
- Carpal Tunnel Syndrome (CTS) and Lumbar Spinal Stenosis: These conditions can sometimes be manifestations of ATTR amyloidosis, where amyloid deposits affect nerves and surrounding tissues. One trial each is exploring the use of 124I-evuzamitide to image amyloid in these specific areas.
In total, 4 trials have been conducted or are ongoing, enrolling a total of 279 participants to evaluate the effectiveness of 124I-evuzamitide as an amyloid imaging agent.
Dosing
Based on current clinical trial data, 124I-evuzamitide is administered as a single intravenous injection. The typical dose studied is approximately 1 mCi (±10%), which corresponds to less than <1.5 mg peptide.
Following the administration of 124I-evuzamitide, PET-CT imaging is performed to evaluate the uptake of the agent in the body. This imaging usually takes place approximately 4 ± 1 hours after the injection. The purpose of this dosing and imaging schedule is to allow sufficient time for the peptide to bind to amyloid deposits and for unbound agent to clear, enabling clear visualization of the target areas.
The studies have explored various investigational settings, including biodistribution and use in patients receiving different amyloid stabilizer or silencer therapies, to understand the drug's behavior and imaging capabilities.
Side Effects
No side effect data for 124I-evuzamitide was provided for this drug reference article.
Clinical Trial Results
Clinical trial results for 124I-evuzamitide primarily focus on its use in positron emission tomography/computed tomography (PET/CT) to measure potential therapeutic response in patients with transthyretin amyloidosis (ATTR). The study NCT05635045 evaluated evuzamitide uptake in patients receiving various ATTR treatments.
One key outcome measured the median percentage change in injected dose (%ID) of evuzamitide uptake. The median change was 0.8 percent for patients receiving silencer-only therapy. For those on a combination of stabilizer and silencer (Tafamidis + Patisiran), the median change was 1.3 percent. Patients treated with Vutrisiran + Diflunisal (stabilizer and silencer) showed a median change of 0.3 percent, while those on stabilizer-only therapy had a median change of 0.2 percent.
Another important measure was the median uptake of evuzamitide as an indicator of cardiac amyloid activity (CAA), reported in grams. Lower values generally suggest less amyloid accumulation. The median CAA was:
- 852.8 grams for patients on silencer-only therapy.
- 952.5 grams for patients on Tafamidis + Patisiran (stabilizer and silencer).
- 155.4 grams for patients on Vutrisiran + Diflunisal (stabilizer and silencer).
- 180.2 grams for patients on stabilizer-only therapy.
The combination of Vutrisiran + Diflunisal showed the lowest median cardiac amyloid activity, suggesting less amyloid burden compared to other groups.
The study also assessed the median uptake of evuzamitide as measured by the volume of interest in milliliters, where lower volumes indicate less amyloid. The median volume of interest was:
- 253.6 mL for patients on silencer-only therapy.
- 177.2 mL for patients on Tafamidis + Patisiran (stabilizer and silencer).
- 39.6 mL for patients on Vutrisiran + Diflunisal (stabilizer and silencer).
- 78.7 mL for patients on stabilizer-only therapy.
Consistent with the cardiac amyloid activity findings, the group receiving Vutrisiran + Diflunisal demonstrated the lowest median volume of interest, indicating the smallest measured amyloid volume among the evaluated treatment regimens.