New data presented at RSNA on use of Bayer's Gadavist® (gadobutrol) injection in children less than 2 years of age

- Pharmacokinetic profile and safety of gadobutrol in pediatric population less than 2 years of age was evaluated

- Study data found that the pharmacokinetic profile and safety of Gadavist® (gadobutrol) at standard dose (0.1 mmol/kg) was similar to adults and children 2 years of age and older

- Gadavist is not FDA approved for use in children less than 2 years of age; This investigational use is currently under FDA review

News provided by

Bayer HealthCare

Dec 03, 2014, 04:00 ET

WHIPPANY, N.J., Dec. 3, 2014 /PRNewswire/ -- Data from a Bayer study in children (infants) less than 2 years of age will be presented today at the 2014 Radiological Society of North America (RSNA) Scientific Assembly and Annual Meeting.¹ The primary endpoint of the study was the evaluation of the pharmacokinetics of Gadavist^® (gadobutrol) injection in plasma at the standard dose of 0.1 mmol/kg body weight.¹ Safety was a secondary endpoint and the study also included a qualitative assessment of efficacy.¹

Pharmacokinetics (PK) is the evaluation of the time required for a drug, once administered, to be distributed in the body and excreted, for example in the urine, and depends on patient-related factors as well as the drug's chemical properties.

The data showed that the gadobutrol PK profile was similar to the PK profile in older children and adults and investigators also observed similar safety of gadobutrol in this pediatric population.¹

Dr. Ravi Bhargava, study investigator and pediatric radiologist, University of Alberta, Edmonton, Canada said, "Our study found that gadobutrol is distributed and eliminated from the body in children under the age of 2 in a similar way to adults and older children."

"Use of Gadavist in children less than 2 years of age to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system is currently under FDA review and FDA has designated this a priority review. Currently there are no gadolinium-based contrast agents, including Gadavist, approved for use in pediatric patients younger than 2 years of age in the U.S.," said Christiane Pering, Chief Medical Officer (CMO) and Head of Innovation, Bayer Medical Care.

About the Study
The study enrolled 47 children with ages spanning from term newborn infants to 23 months with normal renal function from nine centers across the U.S., Canada and Europe. Forty-four children were evaluated for safety and efficacy and 43 were eligible for a PK profile, including nine term newborns less than 2 months of age.^1,2

The study found that the gadobutrol adverse event (AE) profile was consistent with what has been seen in older populations.¹ The most common non-serious AEs unrelated to gadobutrol were cough, nasopharyngitis, rhinitis, pyrexia and vomiting.² In one patient, vomiting was reported as a mild adverse drug reaction (ADR) to gadobutrol. Serious AEs were unrelated to gadobutrol and were reported in three out of 44 subjects.¹

The study abstract, "Open-label, multicenter, pharmacokinetic and safety study in children below 2 years of age undergoing a contrast-enhanced MRI with an intravenous injection of a single standard dose of gadobutrol" is being presented December 3, at 3:30 p.m. CST at the RSNA congress.¹

About Gadavist
Gadavist (gadobutrol) injection was first approved in the U.S. in March 2011 for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system. Gadavist was further approved in June 2014 in the U.S. for intravenous use with MRI of the breast to assess the presence and extent of malignant breast disease.

Gadavist, also known as Gadovist^® and Gadovist^® 1.0 in other regions, is the U.S. brand name of the aqueous 1.0M solution of gadobutrol, a gadolinium (Gd)-based extracellular contrast agent with a macro-molecular structure for magnetic resonance imaging (MRI). The safety profile of Gadavist has been established in clinical trials involving 5,748 patients. Please see Important Safety Information, including Boxed Warning below.

IMPORTANT SAFETY INFORMATION³

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<30mL/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. Analphylactoid and anaphylactic reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist administration. Patients with any history of a reaction to contrast media, bronchial asthma, and/or allergic disorders may have an increased risk for a hypersensitivity reaction to Gadavist.

Acute Kidney Injury: In patients with chronic renal impairment, acute kidney injury sometimes requiring dialysis has been observed with the use of some 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. Avoid intramuscular administration of Gadavist.

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.

Adverse reactions: The most frequent adverse reactions (>0.5%) associated with Gadavist in clinical studies were headache (1.5%), nausea (1.1%), and dizziness (0.5%).

Please see full prescribing information at
http://labeling.bayerhealthcare.com/html/products/pi/gadavist_PI.pdf

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.9 billion (2013), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare's aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 56,000 employees (Dec. 31, 2013) and is represented in more than 100 countries. More information at www.healthcare.bayer.com.

Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup 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

References:

Hahn G et al. Open-label, Multicenter, Pharmacokinetic and Safety Study in Children Below 2 Years of Age Undergoing a Contrast-enhanced MRI with an Intravenous Injection of a Single Standard Dose of Gadobutrol. Abstract #SSM20-04. 2014 Radiological Society of North America (RNSA) Scientific Assembly and Annual Meeting, November 30 - December 5, 2014, Chicago, IL, USA. rsna2014.rsna.org/program/details/?emID=14008140 Accessed October 16, 2014.
Bayer AG data on file - clinical overview and study synopsis.
Gadavist^® (gadobutrol) Prescribing Information. Whippany, New Jersey, USA: Bayer Healthcare Pharmaceuticals, Inc.; October 2014.