Guerbet Prepares for Launch of Elucirem (Gadopiclenol) injection, High-Relaxivity MRI Contrast Agent

Please see below Important Safety Information for Elucirem™

As radiology searches for ways to reduce patient exposure to gadolinium during magnetic resonance imaging (MRI) scans, a new tool has become available: Gadopiclenol injection, a new high-relaxivity contrast agent that will be marketed by Guerbet as Elucirem™.

Gadolinium contrast is essential for enhancing the quality of MRI scans to make it easier for radiologists to identify pathology. But gadolinium has also been linked to several undesirable phenomena, including nephrogenic systemic fibrosis (NSF), a debilitating skin disease, and gadolinium deposition, in which trace elements of gadolinium remain in patient tissue. 

Fortunately, the radiology community has been effective in reducing gadolinium exposure over the years. The incidence of NSF has practically disappeared by screening patients before their MRI scans in order to identify those who might have renal problems that could lead to the condition. Meanwhile, gadolinium deposition has also been reduced by cutting back or eliminating the use of linear gadolinium-based contrast agents (GBCAs) and substituting macrocyclic gadolinium agents instead. 

But what if you could reduce gadolinium exposure even further? That’s what Guerbet has done with Gadopiclenol injection, a macrocyclic GBCA that has much higher relaxivity than previous MRI contrast agents on the market. In general terms, relaxivity can be thought of as the potency of a contrast agent – for a given dose, how it shortens the T1 of a given tissue during an MRI scan.

FDA reviewed this novel drug product under priority review for unmet medical needs, and approved the drug in September 2022. Guerbet is now working on getting approvals for Elucirem™ in other countries, according to David Hale, CEO of Guerbet.

In fact, the arrival of Elucirem™ in countries in Europe could be a particularly welcome development, according to Hale. European regulatory authorities were more aggressive than the FDA in ordering the removal of linear MRI contrast agents from the market – and these agents tended to have higher relaxivity than the macrocyclic agents that replaced them.

High-relaxivity contrast agents like Elucirem™ have a number of benefits for patients. The amount of gadolinium that’s used in an Elucirem™ exam can be cut in half, reducing patient exposure to the element. This is a particularly important consideration for patients who require multiple scans for their clinical issue, according to Jared Houk, commercial vice president for North America at Guerbet.

Guerbet also points out that in clinical research conducted to support the company’s FDA submission for Elucirem™, researchers found that image quality of half-dose Elucirem™ exams was found to be noninferior to full-dose exams performed with other contrast agents.

Elucirem™ may also have potential environmental benefits. Gadolinium is an extremely persistent element, and research studies have found that gadolinium levels in the environment – like rivers, lakes, and bays – are sometimes higher in areas that are closer to medical centers. It’s believed this is due to gadolinium excreted by patients after their MRI scans into municipal water supplies, and then discharged into the environment.

Guerbet is now ramping up its sales and marketing efforts for Elucirem™, according to Houk. A major part of the initiative is educating radiology professionals about the novel benefits of high-relaxivity MRI contrast.

With Elucirem™ added to its portfolio, Guerbet now has two MRI contrast agents available, the other being the company’s Dotarem® (gadoterate meglumine) macrocyclic agent. Guerbet will continue to sell Dotarem, according to Hale.

Hale believes that the unique nature of Elucirem™ – as well as the end-to-end portfolio of Guerbet solutions, including contrast agents, power injectors, and proprietary software – make the company a valued partner for radiology professionals.

References

1. Elucirem [package insert]. Princeton, NJ: Guerbet LLC; 2022
2. Data on file (PICTURE trial. GDX-44-010)
3. Data on file (PROMISE trial. GDX-44-011)
4. Robic, C., Port, M., Rousseaux, O., Louguet, S., Fretellier, N., Catoen, S., Factor, C., Le Greneur, S., Medina, C., Bourrinet, P., Raynal, I., Idée, J. M., & Corot, C. (2019). Physicochemical and Pharmacokinetic Profiles of Gadopiclenol: A New Macrocyclic Gadolinium Chelate With High T1 Relaxivity. Investigative radiology, 54(8), 475–484. https://doi.org/10.1097/RLI.0000000000000563

ELUCIREM^TM (gadopiclenol) injection Important Safety Information

Indications and Usage

ELUCIREM^TM (gadopiclenol) injection is indicated in adult and pediatric patients aged 2 years and older for use with magnetic resonance imaging (MRI) 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).

Contraindications

History of hypersensitivity reactions to ELUCIREM.

Warnings and Precautions

• Hypersensitivity Reactions: With GBCAs, serious hypersensitivity reactions have occurred. In most cases, initial symptoms occurred within minutes of GBCA administration and resolved with prompt emergency treatment. Before ELUCIREM administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to ELUCIREM.
• Gadolinium Retention: Gadolinium is retained for months or years in several organs. Linear GBCAs cause more retention than macrocyclic GBCAs. Consequences of gadolinium retention in the brain have not been established. Pathologic and clinical consequences of GBCA administration and retention in skin and other organs have been established in patients with impaired renal function. While clinical consequences of gadolinium retention have not been established in patients with normal renal function, certain patients might be at higher risk. These include patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions. Consider the retention characteristics of the agent when choosing a GBCA for these patients. Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible
• Acute Kidney Injury: In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent. Do not exceed the recommended dose.
• Extravasation and Injection Site Reactions: Injection site reactions such as injection site pain have been reported in the clinical studies with ELUCIREM. Extravasation during ELUCIREM administration may result in tissue irritation. Ensure catheter and venous patency before the injection of ELUCIREM.
• Interference with Visualization of Lesions Visible with Non-Contrast MRI: As with any GBCA, ELUCIREM may impair the visualization of lesions seen on non-contrast MRI. Therefore, caution should be exercised when Gadopiclenol MRI scans are interpreted without a companion non-contrast MRI scan. 

Adverse Reactions:

In clinical trials, the most frequent adverse reactions that occurred in > 0.2% of patients who received ELUCIREM included: injection site pain, headache, nausea, injection site warmth, injection site coldness, dizziness, and localized swelling.

Adverse reactions that occurred with a frequency ≤ 0.2% in patients who received 0.05 mmol/kg BW ELUCIREM included:  maculopapular rash, vomiting, worsened renal impairment, feeling hot, pyrexia, oral paresthesia, dysgeusia, diarrhea, pruritus, allergic dermatitis, erythema, injection site paresthesia, Cystatin C increase, and blood creatinine increase.

Use in Specific Populations

• Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. There are no available data on ELUCIREM use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
• Lactation: There are no data on the presence of ELUCIREM in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk.
• Pediatric Use: The safety and effectiveness of ELUCIREM have not been established in pediatric patients younger than 2 years of age.
• Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
• Renal Impairment: In patients with renal impairment, the exposure of gadopiclenol is increased compared to patients with normal renal function. This may increase the risk of adverse reactions such as nephrogenic systemic fibrosis (NSF). Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities. No dose adjustment of ELUCIREM is recommended for patients with renal impairment. ELUCIREM can be removed from the body by hemodialysis

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch  or call 1-800-FDA-1088.

Please see the full Prescribing Information, including the patient Medication Guide, for additional important safety information.

For Dotarem™ Full Prescribing Information click here  http://www.dotarem-us.com/Dotarem_PI_Oct2019_CLEAN.pdf  

For Elucerim™ Full Prescribing Information https://www.elucirem.com/media/i5hhrokj/elucirem-uspi.pdf

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