FDA approves Bayer’s Ultravist® (iopromide) injection for contrast-enhanced mammography

• Ultravist™-300, -370 is now the only contrast agent in the U.S. indicated to visualize known or suspected lesions of the breast in adults, as an adjunct to mammography and/or ultrasound
• Contrast-enhanced mammography (CEM) is an emerging modality combining digital mammography with the administration of a contrast agent¹
• Strategically expands Bayer’s portfolio in breast imaging, including contrast agents and injectors

Bayer announced today that Ultravist^® (iopromide)-300, -370, its iodine-based contrast agent, has been approved by the U.S. Food and Drug Administration (FDA) for contrast-enhanced mammography (CEM) – making it the only contrast agent approved for this indication. The product can be used to visualize known or suspected lesions of the breast in adults, as an adjunct to mammography and/or ultrasound. CEM is an emerging modality that combines digital mammography with the administration of a contrast agent, such as Ultravist, to help identify breast lesions.1

The new FDA approved indication aligns with the recent increased focus on supplemental imaging needs for women at a higher risk for breast cancer, which may include the 40-50% of U.S. women older than 40 with dense breasts.²

“The approval of Ultravist-300 and -370 in contrast-enhanced mammography gives physicians a new imaging option where conventional mammography might not be enough,” said Dr. Konstanze Diefenbach, Head of Radiology Research and Development, Bayer. “We are pleased to be able to offer additional options for breast imaging to healthcare professionals, as we aim to support them in their role of providing clear answers from diagnosis to care for patients.”

The approval expands upon Bayer's focus on breast imaging, with a portfolio that also includes Gadavist ^® (gadobutrol) injection, a gadolinium-based contrast agent approved for use with MRI (Magnetic Resonance Imaging) to assess the presence and extent of malignant breast disease in adult patients. In 2019, the MEDRAD^® Stellant FLEX Computed Tomography (CT) Injection System with Certegra^® Workstation was also cleared in the U.S. for use in CEM. Through the use of iodine-based x-ray contrast agents, CEM can allow for better visualization of abnormalities in breast tissue that may not be visible with standard mammography.³

About breast cancer and contrast-enhanced mammography

In 2020, there were 2.3 million women diagnosed with breast cancer globally, according to the World Health Organization (WHO).⁴ Contrast-enhanced mammography (CEM) has been demonstrated to help with visualization of lesions in breast tissue and is a relatively low-cost breast imaging examination. CEM is easy to perform in everyday clinical practice and can be used in various clinical settings, such as when routine imaging produces inconclusive findings. It can also be a helpful tool when breast MRI is unavailable or contraindicated.⁵

About Ultravist

INDICATIONS and IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE

Intra‐arterial Procedures*: Ultravist® is indicated for: • Cerebral arteriography and peripheral arteriography in adults; • Coronary arteriography and left ventriculography, visceral angiography, and aortography in adults; • Radiographic evaluation of cardiac chambers and related arteries in pediatric patients aged 2 years and older.

Intravenous Procedures*: Ultravist® is indicated for: • Excretory urography in adults and pediatric patients aged 2 years and older; • Contrast Computed Tomography (CT) of the head and body (intrathoracic, intra-abdominal, and retroperitoneal regions) for the evaluation of neoplastic and non-neoplastic lesions in adults and pediatric patients aged 2 years and older; • Contrast mammography to visualize known or suspected lesions of the breast in adults, as an adjunct following mammography and/or ultrasound.

*Specific concentrations and presentations of Ultravist® are recommended for each type of imaging procedure [see Dosage and Administration (2.2, 2.3, 2.4)] in the Full Prescribing Information]

IMPORTANT SAFETY INFORMATION

WARNING: RISK ASSOCIATED WITH INTRATHECAL USE

Intrathecal administration, even if inadvertent, may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. ULTRAVIST is not approved for intrathecal use.

Risks Associated with Intrathecal Use: Intrathecal administration, even if inadvertent, can cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Ultravist^® is for intra-arterial or intravenous use only. Ultravist^® is not approved for intrathecal use.

Hypersensitivity Reactions: Ultravist^® can cause life-threatening or fatal hypersensitivity reactions including anaphylaxis. Manifestations include respiratory arrest, laryngospasm, bronchospasm, angioedema, and shock. Most severe reactions develop shortly after the start of injection (e.g., within 1 to 3 minutes), but delayed reactions can also occur. There is increased risk of hypersensitivity reactions in patients with a history of previous reaction to a contrast agent and known allergic disorders, or other hypersensitivities. Premedication with antihistamines or corticosteroids does not prevent serious life-threatening reactions but may reduce both their incidence and severity. Obtain a history of allergy, hypersensitivity, or hypersensitivity reactions to iodinated contrast agents and have emergency resuscitation equipment and trained personnel available prior to Ultravist^® administration. Monitor all patients for hypersensitivity reactions.

Acute Kidney Injury: Acute kidney injury, including renal failure, may occur after administration. Risk factors include: pre-existing renal insufficiency, dehydration, diabetes mellitus, congestive heart failure, advanced vascular disease, elderly age, concomitant use of nephrotoxic or diuretic medications, multiple myeloma or other paraproteinemia, and repetitive and/or large doses of Ultravist® . Use the lowest necessary dose of Ultravist® in patients with renal impairment. Hydrate patients prior to and following Ultravist® administration. Do not use laxatives, diuretics, or preparatory dehydration prior to Ultravist® administration.

Cardiovascular Adverse Reactions: In patients with cardiac and / or renal disease, hemodynamic disturbances including shock and cardiac arrest may occur during or shortly after administration of Ultravist®. Hypotensive collapse and shock have occurred. Cardiac decompensation, serious arrhythmias, and myocardial ischemia or infarction can occur during coronary arteriography and ventriculography. Use the lowest necessary dose of ULTRAVIST in patients with congestive heart failure. Always have emergency resuscitation equipment and trained personnel available. Monitor all patients for severe cardiovascular reactions.

Thromboembolic Events: Serious, in some cases fatal, thromboembolic events causing myocardial infarction and stroke can occur during angiography procedures. During these procedures, increased thrombosis and activation of the complement system can occur. Risk of thromboembolic events can be influenced by: length of procedure, catheter and syringe material, underlying disease state, and concomitant medications. To decrease thromboembolic events, use meticulous angiographic techniques and minimize the length of the procedure. Avoid blood remaining in contact with syringes containing iodinated contrast agents, which increases the risk of clotting. Avoid angiography in patients with homocystinuria because of the risk of inducing thrombosis and embolism.

Extravasation and Injection Site Reactions: Extravasation can occur, particularly in patients with severe arterial or venous disease. In addition, injection site reactions such as pain and swelling at the injection site can also occur. Ensure intravascular placement of catheters prior to injection. Monitor patients for extravasation and advise patients to seek medical care for progression of symptoms.

Thyroid Storm in Patients with Hyperthyroidism: Thyroid storm has occurred after the intravascular use of iodinated contrast agents in patients with hyperthyroidism or with an autonomously functioning thyroid nodule. Evaluate the risk in such patients before use of Ultravist®.

Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age: Thyroid dysfunction characterized by hypothyroidism or transient thyroid suppression has been reported after both single exposure and multiple exposures to iodinated contrast media (ICM) in pediatric patients 0 to 3 years of age. Younger age, very low birth weight, prematurity, underlying medical conditions affecting thyroid function, admission to neonatal or pediatric intensive care units, and congenital cardiac conditions are associated with an increased risk of hypothyroidism after ICM exposure. After exposure to ICM, individualize thyroid function monitoring based on underlying risk factors, especially in term and preterm neonates. The safety and effectiveness of Ultravist® in pediatric patients younger than 2 years of age have not been established, and Ultravist® is not approved for use in pediatric patients younger than 2 years of age.

Hypertensive Crisis in Patients with Pheochromocytoma: Hypertensive crisis in patients with pheochromocytoma has occurred with iodinated contrast agents. Closely monitor patients when administering Ultravist® if pheochromocytoma or catecholamine-secreting paragangliomas are suspected. Inject the minimum amount of Ultravist® necessary and have measures for treatment of a hypertensive crisis readily available.

Sickle Cell Crisis in Patients with Sickle Cell Disease: Iodinated contrast agents may promote sickling in individuals who are homozygous for sickle cell disease. Hydrate patients prior to and following administration and use only if the necessary imaging information cannot be obtained with alternative imaging modalities.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Ultravist® to patients with a history of a severe cutaneous adverse reaction to Ultravist®.

Interference with Laboratory Tests: Ultravist® can interfere with protein-bound iodine test.

Common Adverse Reactions: Common adverse reactions (>1%) are headache, nausea, injection site and infusion site reactions, vasodilatation, vomiting, back pain, urinary urgency, chest pain, pain, dysgeusia, and abnormal vision.

Please see Full Prescribing Information for Ultravist®.

About Gadavist

INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

Gadavist^® (gadobutrol) injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI):

• To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients including term neonates.
• To assess the presence and extent of malignant breast disease in adult patients.
• To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).

Gadavist^® is indicated for use in magnetic resonance angiography (MRA):

• To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients including term neonates.

IMPORTANT SAFETY INFORMATION

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

Gadolinium-based contrast agents (GBCAs) increase the risk for 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. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs.

• The risk of NSF appears highest among patients with:
  • Chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or
  • Acute kidney injury
• Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing.
• For patients at highest risk for NSF, do not exceed the recommended GADAVIST dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration.

Contraindication and Important Information about Hypersensitivity Reactions: Gadavist^® is contraindicated in patients with history of severe hypersensitivity reactions to Gadavist^®. Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist^® administration. Before Gadavist^® 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 Gadavist^®.

Gadolinium Retention: Gadolinium is retained for months or years in several organs. Linear GBCAs cause more retention than macrocyclic GBCAs. At equivalent doses, retention varies among the linear agents. Retention is lowest and similar among the macrocyclic GBCAs. Consequences of gadolinium retention in the brain have not been established, but they have been established in the skin and other organs 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 and minimize repetitive GBCA studies, when possible.

Acute Kidney Injury: In patients with chronic renal impairment, acute kidney injury sometimes requiring dialysis has been observed with the use of GBCAs. Do not exceed the recommended dose; the risk of acute kidney injury may increase with higher than recommended doses.

Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of Gadavist^®. Extravasation into tissues during Gadavist^® administration may result in moderate irritation.

Overestimation of Extent of Malignant Disease in MRI of the Breast: Gadavist^® MRI of the breast overestimated the histologically confirmed extent of malignancy in the diseased breast in up to 50% of the patients.

Low Sensitivity for Significant Arterial Stenosis: The performance of Gadavist^® MRA for detecting arterial segments with significant stenosis (>50% renal, >70% supra-aortic) has not been shown to exceed 55%. Therefore, a negative MRA study alone should not be used to rule out significant stenosis.

Adverse Reactions: The most frequent (≥0.5%) adverse reactions associated with Gadavist^® in clinical studies were headache (1.7%), nausea (1.2%) and dizziness (0.5%).

Please see Full Prescribing Information for Gadavist^® (Vials and Syringes).

Please see Full Prescribing Information for Gadavist^® (Imaging Bulk Package).

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com.

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Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

PP-ULT-US-0096-1 June 2023

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