Nephrogenic Fibrosing Dermopathy

Ascelia Pharma AB (publ) (ticker: ACE), a biotech focused on improving the life of people living with rare cancer conditions, today announced that liver imaging drug candidate, Orviglance®, significantly improved visualization of focal liver lesions, successfully meeting the primary endpoint in the pivotal Phase 3 study SPARKLE. Investors and analysts are invited to the virtual Investor Update: “Bringing Orviglance to Patients”, on Tuesday, 7 May at 14:00 CEST The Phase 3 study demonstrated strong superiority in visualization of focal liver lesions with Orviglance (CMRI) vs. unenhanced MRI with statistical significance for all three readers (<0.001) Orviglance is in development as a first-in-class contrast agent for use in liver MRI in patients with severely impaired kidney function and has been granted FDA Orphan Drug Designation Orviglance addresses a global USD 800 million market annually The Phase 3 data marks the completion of Orviglance clinical development with nine studies in 286 patients and healthy volunteers Submission of the New Drug Application (NDA) the US Food and Drug Administration (FDA) is expected by mid-2025 Investors, analysts and media are invited to the virtual Investor Update and live Q&A on next steps: “Bringing Orviglance to Patients”, on Tuesday, 7 May 2024 at 14:00 CES The pivotal Phase 3 study, SPARKLE, successfully met the primary endpoint and demonstrated that the company’s magnetic resonance imaging (MRI) contrast agent, Orviglance significantly improved the visualization of focal liver lesions compared to unenhanced MRI. The results for all three readers were highly statistically significant (P values <0.001). The reliability of the data is strong and conclusive for all readers – this includes an acceptable level of variability. Common adverse events in this vulnerable patient population were in line with previous studies with Orviglance, such as mild- to moderate nausea. No serious adverse drug reactions were observed “We are thrilled to announce these strong and convincing Phase 3 results for Orviglance. This is the most significant milestone achievement for Ascelia Pharma so far”, said Magnus Corfitzen, CEO of Ascelia Pharma. “Following considerable challenges during the SPARKLE study, we are very excited to complete the Orviglance clinical development with these strong results in Phase 3. We now look forward to advancing Orviglance through the registration process and make it available for patients.” The Company will now focus on bringing Orviglance through the regulatory submission and approval process. In parallel, we will continue to advance launch readiness and dialogue with potential commercialization partners to make Orviglance available to patients who need high-quality liver imaging without gadolinium-related safety risk. “On behalf of the entire Ascelia Pharma team, I would like to thank patients and investigators involved in the SPARKLE study as well as other partners instrumental in completing the successful data read-out. We look forward to discussing the results with the medical community and regulatory authorities”, said Magnus Corfitzen. The Company expects to submit the New Drug Application (NDA) the US Food and Drug Administration (FDA) by mid-2025 to obtain regulatory approval. Investors, analysts, and media are invited to the virtual Investor Update: “Bringing Orviglance to Patients”, on Tuesday, 7 May 2024 at 14:00 CEST. In this update and live Q&A, executive management will further explain the strong headline results and share plans for the upcoming regulatory and commercialization activities. A link to the event will be available on the company’s website ( com). Clinical development of Orviglance has now been completed with consistent positive efficacy and safety data from 286 patients and healthy volunteers in nine studies, of which the SPARKLE is the last and pivotal study. Patient enrollment in the global multi-center SPARKLE study was completed early 2023, with MRI data from 85 patients with known or suspected focal liver lesions and severely impaired kidney function. In accordance with regulatory requirements, the improvement of visualization of lesions was evaluated by three independent radiologist readers. In mid-2023, the unexpected discovery of high intra-reader variability in the study image scoring by the readers prevented the Company from evaluating the efficacy data from SPARKLE. Therefore, a new evaluation of the images with new readers was required. The company successfully completed the re-evaluation according to the planned timeline with the announcement today. Orviglance has been granted an Orphan Drug Designation by the US Food and Drug Administration (FDA) for liver MRI in patients with severely impaired kidney function. These patients have the highest risk of developing the serious and potentially fatal condition Nephrogenic Systemic Fibrosis (NSF) after exposure to the currently available gadolinium-based contrast agents. Regulatory bodies have issued warnings for the use of these agents in this vulnerable patient population. Therefore, there is a need for an alternative solution to detect and visualize focal liver lesions in patients with impaired kidney function, who today typically receive inferior unenhanced MRI. Liver MRI is a cornerstone in cancer care, as liver metastases are common in many cancer types and often the cause of mortality. Orviglance aims to give patients with impaired kidney function access to safe and effective liver imaging to live longer and healthier lives. The unmet need for these patients represents an addressable market potential of USD 800 million globally. *The Company considers mid-2025 to be the period from the second half of Q2 to the first half Q3. Contacts Magnus Corfitzen, CEO Email: moc@ascelia.com Tel: +46 735 179 118 Julie Waras Brogren, Deputy CEO (Finance, Investor Relations & Commercial) Email: jwb@ascelia.com Tel: +46 735 179 116 This information was submitted for publication, through the agency of the contact persons set out above. About Us Ascelia Pharma is a biotech company focused on orphan oncology treatments. We develop and commercialize novel drugs that address unmet medical needs and have a clear development and market pathway. The company has two drug candidates – Orviglance and Oncoral – in clinical development. Ascelia Pharma has global headquarters in Malmö, Sweden, and is listed on Nasdaq Stockholm (ticker: ACE). For more information, please visit About Orviglance Orviglance (manganese chloride tetrahydrate) is a novel oral contrast agent for MR-imaging developed to improve the detection and visualization of focal liver lesions (including liver metastases and primary tumors) in patients with reduced kidney function. These patients are at risk of serious side effects from the currently available class of gadolinium-based contrast agents. Orviglance, has been granted an Orphan Drug Designation by the US Food and Drug Administration (FDA). A clinical program of nine studies, including the pivotal global Phase 3 study SPARKLE, has successfully been completed with strong and consistent efficacy and safety results. About Oncoral Oncoral is a novel irinotecan chemotherapy tablet developed initially for the treatment of gastric cancer. Irinotecan chemotherapy has an established potent anti-tumor effect. Oncoral is a daily tablet with the potential to offer better patient outcomes with improved safety following the daily dosing at home compared to intravenous high-dose infusions at the hospital. Following successful Phase 1 results, Oncoral is now prepared for Phase 2 clinical development. This information is information that Ascelia Pharma is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact persons set out above, at 2024-05-02 11:12 CEST. Attachments Ascelia Pharma Successfully Meets Primary Endpoint with Strong Headline Results in Orviglance Phase 3 Study

ELUCIREM™ (gadopiclenol) Injection Safety Data Poster Presentation First Place "Image of the Year" Winner of Applied Radiology and Guerbet 'Elucirem | The Reveal Image Challenge' to be Announced PRINCETON, N.J., Nov. 27, 2023 /PRNewswire/ -- Guerbet, a global leader in medical imaging with more than 30 years of experience in MRI, announced today its schedule of activities at the 2023 Radiological Society of North America (RSNA) Scientific Assembly and Annual Meeting from November 26-30 in Chicago, IL. In addition to the Guerbet exhibit (booth #1711), the company will be presenting safety data in an abstract titled "Safety of gadopiclenol for magnetic resonance imaging (MRI): a pooled analysis of eight studies." The session number W3-STCE1, will be presented as a scientific session on Wednesday, November 29 at 10:00-10:30 a.m. CST. Additionally, the "Elucirem | The Reveal Image Challenge" "Image of the Year" winner will be announced and unveiled at the Guerbet booth at RSNA on Monday, November 27th at 11:00 a.m. CST. The challenge, which was developed in partnership with Applied Radiology, provided MR imaging professionals with an opportunity to reveal their MR imaging potential and to share their MRI images using Elucirem™ (gadopiclenol) injection. A series of winning images were selected each month starting in May 2023, having been evaluated by a review committee, including MRI thought leaders and educators, Applied Radiology board members and Guerbet associates. Winning images were featured on the Applied Radiology website and social media platforms. All winning images will be available for viewing at the Guerbet RSNA booth. Poster Presentations Spotlight at the RSNA Innovation Theater Jeffrey H Maki, MD, PhD, Professor of Radiology and Director of MRI at the University of Colorado in Denver will be presenting "Relaxation properties of GBCAs In Vitro, in human blood – their unique behavior might surprise you" at 1:00 p.m. CST on Monday, November 27th. This presentation, which will take place in the RSNA Innovation Theater Exhibitor Pavillion in the South Hall, is based on a study done to measure T1 and T2 relaxivity In Vitro, in human blood. Digital Solutions Featured at Booth #1711 In addition to showcasing diagnostic and interventional solutions, Guerbet will also feature its digital and AI software-based products that help to close the loop with the smart connectivity between monitoring and reporting. Products that will be featured include: Dose & Care®, a state-of-the-art digital solution for monitoring patient exposure to X-rays that is compatible with all types of ionizing modalities and collects data to provide a record of patient exposure Contrast & Care®, an injection data management solution that enables imaging centers to collect, archive, examine, and share injection data, including data on contrast products, adverse events, injector activity, information on estimated glomerular filtration rate, and other risk factors before a clinical exam Icobrain, a cloud-based AI solution designed to quantify disease specific brain structures on MR and CT Galileo, an educational web-based case review platform to help train radiology residents Myrian®, a universal image processing solution that can be integrated into all healthcare information systems Optistar™ Elite, a dual head contrast delivery system with an ultrasonic motor that makes it non-magnetic, built for long lasting performance and now has the new Fractional Dosing capabilities About Elucirem™ This next generation GBCA from Guerbet, highly stable macrocyclic gadolinium-based contrast agent (GBCA), gadopiclenol has the highest relaxivity in its class for magnetic resonance imaging (MRI) and is indicated for use in adults and children aged 2 years and older.1,2 Elucirem™ requires only half the gadolinium dose of conventional non-specific GBCAs, addressing practitioners' concerns about gadolinium exposure.3,4 Elucirem™ (Gadopiclenol) injection 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).1 Guerbet received FDA approval of Elucirem™ (NDA 216986) on September 21, 2022 after priority review, a designation assigned to applications for drugs that provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions compared to available therapies.5 GBCAs improve the contrast between lesions and surrounding tissues by accelerating the relaxation of protons thanks to interaction with gadolinium atoms. Gadopiclenol, the active drug substance of Elucirem™, has been designed to enable twice as much interaction, resulting in the highest relaxivity among all non-specific GBCAs.2 This allows use at half the conventional gadolinium dose to reveal high quality images. Elucirem is manufactured by Liebel-Flarsheim™ Company LLC, a Guerbet Group company, in Raleigh, North Carolina. About Guerbet At Guerbet, we build lasting relationships so that we enable people to live better. That is our purpose. We are a global leader in medical imaging, offering a comprehensive range of pharmaceutical products, medical devices, and digital and AI solutions for diagnostic and interventional imaging. As pioneers in contrast products for over 95 years, with more than 2,600 employees worldwide, we continuously innovate and devote 10% of our revenue to research and development in four centers in France, Israel, and the United States. Guerbet (GBT) is listed on Euronext Paris (segment B – mid caps) and generated 753 million euros in revenue in 2022. For more information, please visit . About Gadopiclenol Gadopiclenol, initially invented by Guerbet with subsequent contribution of Bracco intellectual property, is a macrocyclic gadolinium-based contrast agent (GBCA) with high relaxivity. The efficacy and safety of Gadopiclenol have been evaluated in MRI of the central nervous system (brain, spine, and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system) in adult and pediatric patients aged 2 years and older. (refer to the approved USPI for full information). Details on Phase III clinical trials are available on : Efficacy and Safety of Gadopiclenol for Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) Full Text View - ClinicalTrials.gov Efficacy and Safety of Gadopiclenol for Body Magnetic Resonance Imaging (MRI) - Full Text View - ClinicalTrials.gov Gadopiclenol is currently in the process of examination by the European Medicines Agency. ELUCIREM™ (gadopiclenol) injection Important Safety Information Indications and Usage ELUCIREM™ (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 Nephrogenic Systemic Fibrosis: GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease as well as patients with acute kidney injury. 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 excreted 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 or call 1-800-FDA-1088. Please see the full Prescribing Information, including the Medication Guide, for additional important safety information. 1Elucirem [package insert]. Princeton, NJ: Guerbet LLC; 2022 2 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. 3 Loevner LA, Kolumban B, Hutóczki G, et al. Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System: The PICTURE Randomized Clinical Trial. Invest Radiol. 2023;58(5):307-313. doi:10.1097/RLI.0000000000000944 4 Kuhl C, Csőszi T, Piskorski W, et al. Efficacy and safety of half-dose gadopiclenol versus full-dose gadobutrol for contrast-enhanced body MRI. Radiology. 2023; 308(1). doi:10.1148/radiol.222612 5 US FDA. Priority Review. Available at: . Accessed August 22, 2022 SOURCE Guerbet

ELUCIREM™ (gadopiclenol) Injection Safety Data Poster Presentation First Place "Image of the Year" Winner of Applied Radiology and Guerbet 'Elucirem | The Reveal Image Challenge' to be Announced PRINCETON, N.J., Nov. 2, 2023 /PRNewswire/ -- Guerbet, a global leader in medical imaging with more than 30 years of experience in MRI, announced today its schedule of activities at the 2023 Radiological Society of North America (RSNA) Scientific Assembly and Annual Meeting from November 26-30 in Chicago, IL. In addition to the Guerbet exhibit (booth #1711), the company will be presenting safety data in an abstract titled "Safety of gadopiclenol for magnetic resonance imaging (MRI): a pooled analysis of eight studies." The session number W3-STCE1, will be presented as a scientific session on Wednesday, November 29 at 10:00-10:30 a.m. CST. Additionally, the "Elucirem | The Reveal Image Challenge" "Image of the Year" winner will be announced and unveiled at the Guerbet booth at RSNA on Monday, November 27th at 11:00 a.m. CST. The challenge, which was developed in partnership with Applied Radiology, provided MR imaging professionals with an opportunity to reveal their MR imaging potential and to share their MRI images using Elucirem™ (gadopiclenol) injection. A series of winning images were selected each month starting in May 2023, having been evaluated by a review committee, including MRI thought leaders and educators, Applied Radiology board members and Guerbet associates. Winning images were featured on the Applied Radiology website and social media platforms. All winning images will be available for viewing at the Guerbet RSNA booth. Poster Presentations Spotlight at the RSNA Innovation Theater Jeffrey H Maki, MD, PhD, Professor of Radiology and Director of MRI at the University of Colorado in Denver will be presenting "Relaxation properties of GBCAs In Vitro, in human blood – their unique behavior might surprise you" at 1:00 p.m. CST on Monday, November 27th. This presentation, which will take place in the RSNA Innovation Theater Exhibitor Pavillion in the South Hall, is based on a study done to measure T1 and T2 relaxivity In Vitro, in human blood. Digital Solutions Featured at Booth #1711 In addition to showcasing diagnostic and interventional solutions, Guerbet will also feature its digital and AI software-based products that help to close the loop with the smart connectivity between monitoring and reporting. Products that will be featured include: Dose & Care®, a state-of-the-art digital solution for monitoring patient exposure to X-rays that is compatible with all types of ionizing modalities and collects data to provide a record of patient exposure Contrast & Care®, an injection data management solution that enables imaging centers to collect, archive, examine, and share injection data, including data on contrast products, adverse events, injector activity, information on estimated glomerular filtration rate, and other risk factors before a clinical exam Icobrain, a cloud-based AI solution designed to quantify disease specific brain structures on MR and CT Galileo, an educational web-based case review platform to help train radiology residents Myrian®, a universal image processing solution that can be integrated into all healthcare information systems Optistar™ Elite, a dual head contrast delivery system with an ultrasonic motor that makes it non-magnetic, built for long lasting performance and now has the new Fractional Dosing capabilities About Elucirem™ This next generation GBCA from Guerbet, highly stable macrocyclic gadolinium-based contrast agent (GBCA), gadopiclenol has the highest relaxivity in its class for magnetic resonance imaging (MRI) and is indicated for use in adults and children aged 2 years and older.1,2 Elucirem™ requires only half the gadolinium dose of conventional non-specific GBCAs, addressing practitioners' concerns about gadolinium exposure.3,4 Elucirem™ (Gadopiclenol) injection 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).1 Guerbet received FDA approval of Elucirem™ (NDA 216986) on September 21, 2022 after priority review, a designation assigned to applications for drugs that provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions compared to available therapies.5 GBCAs improve the contrast between lesions and surrounding tissues by accelerating the relaxation of protons thanks to interaction with gadolinium atoms. Gadopiclenol, the active drug substance of Elucirem™, has been designed to enable twice as much interaction, resulting in the highest relaxivity among all non-specific GBCAs.2 This allows use at half the conventional gadolinium dose to reveal high quality images. Elucirem is manufactured by Liebel-Flarsheim™ Company LLC, a Guerbet Group company, in Raleigh, North Carolina. About Guerbet At Guerbet, we build lasting relationships so that we enable people to live better. That is our purpose. We are a global leader in medical imaging, offering a comprehensive range of pharmaceutical products, medical devices, and digital and AI solutions for diagnostic and interventional imaging. As pioneers in contrast products for over 95 years, with more than 2,600 employees worldwide, we continuously innovate and devote 10% of our revenue to research and development in four centers in France, Israel, and the United States. Guerbet (GBT) is listed on Euronext Paris (segment B – mid caps) and generated 753 million euros in revenue in 2022. For more information, please visit . About Gadopiclenol Gadopiclenol, initially invented by Guerbet with subsequent contribution of Bracco intellectual property, is a macrocyclic gadolinium-based contrast agent (GBCA) with high relaxivity. The efficacy and safety of Gadopiclenol have been evaluated in MRI of the central nervous system (brain, spine, and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system) in adult and pediatric patients aged 2 years and older. (refer to the approved USPI for full information). Details on Phase III clinical trials are available on : Efficacy and Safety of Gadopiclenol for Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) Full Text View - ClinicalTrials.gov Efficacy and Safety of Gadopiclenol for Body Magnetic Resonance Imaging (MRI) - Full Text View - ClinicalTrials.gov Gadopiclenol is currently in the process of examination by the European Medicines Agency. ELUCIREM™ (gadopiclenol) injection Important Safety Information Indications and Usage ELUCIREM™ (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 Nephrogenic Systemic Fibrosis: GBCAs increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease as well as patients with acute kidney injury. 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 excreted 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 or call 1-800-FDA-1088. Please see the full Prescribing Information, including the Medication Guide, for additional important safety information. 1Elucirem [package insert]. Princeton, NJ: Guerbet LLC; 2022 2 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. 3 Loevner LA, Kolumban B, Hutóczki G, et al. Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System: The PICTURE Randomized Clinical Trial. Invest Radiol. 2023;58(5):307-313. doi:10.1097/RLI.0000000000000944 4 Kuhl C, Csőszi T, Piskorski W, et al. Efficacy and safety of half-dose gadopiclenol versus full-dose gadobutrol for contrast-enhanced body MRI. Radiology. 2023; 308(1). doi:10.1148/radiol.222612 5 US FDA. Priority Review. Available at: . Accessed August 22, 2022 SOURCE Guerbet