Newly approved MRI contrast agent Gadopiclenol set to boost short supply
The U.S Food and Drug Administration’s (FDA) recent approval of Gadopiclenol injection, a gadolinium-based contrast agent (GBCA) for magnetic resonance imaging (MRI), paves the way for a new marketing paradigm that is designed to ensure the broadest possible access to patients and their healthcare professionals in need of imaging agents.
Gadopiclenol will be independently commercialized by both Bracco Diagnostics (as VUEWAY) and Guerbet (as Elucirem), industry competitors that each played a role in its development. Gadopiclenol was initially invented by Guerbet with subsequent contribution of Bracco intellectual property.
This approval is timely. A recent shortage in contrast agents has caused physicians to make difficult decisions in their choice of contrast agents for patients. Although this recent shortage was for X-ray contrast agents, shifting of patients to MR contrast resulted in a surge in GBCA use by 50%. The commercialization of Gadopiclenol by both companies will expand access to this first-of-its kind contrast agent by one and a half times.
“The approval of Gadopiclenol injection follows Priority Review, which is granted by the FDA for products that are considered significant improvements in safety or effectiveness when compared to standard options,” said Alberto Spinazzi, MD, Chief Medical and Regulatory Officer at Bracco. “This is because Gadopiclenol injection is a first-of-its-kind MRI agent that delivers the highest relaxivity and highest kinetic stability of all GBCAs on the market today. Highly stable, clinical studies showed that VUEWAY injection provides effective contrast enhancement and diagnostic efficacy at half the approved dose of Gadobutrol injection and Gadobenate dimeglumine injection, another high-relaxivity agent. The positive benefit-risk profile of VUEWAY injection has been demonstrated across a large number of indications, including some for which GBCAs had not previously been approved in the United States.” Gadopiclenol is a new macrocyclic gadolinium-based contrast agent with high relaxivity indicated for use in adults and children aged 2 years and older, for contrast-enhanced magnetic resonance imaging (MRI). The product is used to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system.
Gadopiclenol has been widely anticipated. The FDA’s approval is based on two phase three studies – PICTURE (ClinicalTrials.gov Identifier: NCT03996447) and PROMISE (ClinicalTrials.gov Identifier: NCT03986138) –studies comparing Gadopiclenol injection at a dose of 0.05 mmol/kg and Gadobutrol injection at 0.1 mmol/kg in adult patients undergoing MRI. In both studies, comparable lesion detection and visualization in MRI scanning was found, with lower doses of gadolinium compared to other agents already on the market. Gadopiclenol used half the approved dose of the active ingredient versus traditional GBCAs.
Gadopiclenol has been designed with two sites for water molecule exchange to increase relaxivity and contrast, allowing to use it at half the conventional dose of gadolinium compared to other non-specific GBCAs.
A gadolinium-based contrast agent for use with a MRI scanner
Efficacy and safety
The efficacy and safety of Gadopiclenol have been assessed as part of Guerbet’s clinical development plan, with marketing authorization being targeted worldwide.
According to MPR < www.empr.com > Gadopiclenol carries a Boxed Warning associated with an increased risk of nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. Patients with chronic, severe kidney disease (glomerular filtration rate <30mL/min/1.73m2) or acute kidney injury appear to have the highest risk for NSF. Patients should be screened for acute kidney injury and other conditions that may reduce renal function.
The FDA is the first health authority to have approved Gadopiclenol. It is currently in the process of examination by the European Medicines Agency via a centralized procedure.
Guerbet and Bracco Imaging
In December 2021, Guerbet and Bracco Imaging entered into a worldwide collaboration on Gadopiclenol manufacturing and research and development. Gadopiclenol will be commercialized independently under separate brands. Both Guerbet and Bracco Imaging each own valuable intellectual property on Gadopiclenol. Furthermore, after an agreed transition period when Guerbet manufactures Gadopiclenol for both Guerbet and Bracco Imaging, both companies will manufacture Gadopiclenol active ingredient and finished product.
Guerbet will produce Elucirem (Gadopiclenol) in the United States and France. It will be marketed by in the United States in bottle and pre-filled syringe form.
“This strategic collaboration will expand access to this important new contrast agent which has the potential to help improve diagnoses and ultimately improve patient care,” said Cosimo De Pinto, Senior Vice President of Sales and Marketing at Bracco Diagnostics. “By exploring a flexible application of our intellectual property rights, we’ve seen that joining forces has led to meaningful innovation at a faster pace. One of the greatest barriers to health equity and access is overly strict adherence to traditional approaches to knowledge and information sharing. The more we collaborate, the more we unencumber healthcare delivery at moments when it matters most.”
Phase III clinical trials for Gadopiclenol
The approval was primarily based on data from two Phase III studies completed in March 2021 which demonstrated that Elucirem leads to non-inferior results in brain and body MRI at half the gadolinium dose of Gadobutrol The endpoints were met in terms of the diagnostic benefit of injecting Gadopiclenol (0.05 mmol/kg) during MRI examinations, based on two criteria:
1. the superiority of the examination with Gadopiclenol compared to the examination with no contrast agent;
2. the non-inferiority of Gadopiclenol (0.05 mmol/kg) compared to Gadobutrol (0.1 mmol/kg) for the visualization and detection of lesions of the central nervous system and in
the other anatomical areas studied.
No major safety signals were reported during the development of Gadopiclenol, and the adverse reactions reported during the two-Phase III studies were similar for both products administered.
