Bayer HealthCare Pharmaceuticals
Inc., a leader in diagnostic imaging, announced that the U.S. Food
and Drug Administration (FDA) has approved EOVIST(R) (Gadoxetate Disodium)
Injection, a gadolinium-based contrast agent, for intravenous use in
T1-weighted magnetic resonance imaging (MRI) of the liver to detect and
characterize lesions in adults with known or suspected focal liver disease.
The approval makes EOVIST the first organ-specific MRI contrast agent
approved in the United States in more than a decade.
"The approval of EOVIST in the United States marks a significant
achievement in advancing the accurate diagnosis of liver disease," said
Douglas Stefanelli, Vice President and General Manager, Diagnostic Imaging,
Bayer HealthCare Pharmaceuticals. "This milestone demonstrates Bayer
HealthCare Pharmaceuticals' commitment to providing innovative imaging
products that can help improve the lives of patients."
EOVIST is a paramagnetic MRI contrast agent that combines features of
both an extracellular contrast agent and a hepatocyte-specific agent.
EOVIST is administered via an intravenous, bolus injection and has a dual
route of excretion with approximately 50 percent eliminated through the
liver and 50 percent eliminated through the kidney. Detection and
characterization of malignant and benign focal liver lesions with EOVIST
may help enhance diagnostic accuracy and increase diagnostic confidence.
"EOVIST-enhanced images can provide more comprehensive information
about focal liver lesions in a single, short imaging session than was
previously available," said Jeffrey Brown, MD, Professor of Radiology,
Washington University School of Medicine, St. Louis. "With the availability
of EOVIST, our ability to evaluate patients with benign and malignant focal
hepatic lesions will be improved."
The American Cancer Society estimates that 21,370 new cases of primary
liver cancer and intrahepatic bile duct cancer will be diagnosed in the
United States during 2008, and the incidence of liver cancer continues to
increase.(1) Earlier staging of primary tumors with metastases in the
liver, such as colon cancer, may improve treatment decisions and, hence,
the survival rate. This year, approximately 110,000 new cases of colon
cancer will be diagnosed in the United States.(2)
Stefanelli continued, "With EOVIST and Nexavar, Bayer HealthCare
Pharmaceuticals is uniquely positioned to help healthcare professionals
detect and treat liver cancer." Nexavar(R) (sorafenib), an oral anticancer
medicine called a kinase inhibitor, is approved for use in patients with
unresectable hepatocellular carcinoma (HCC).
EOVIST is marketed by Bayer HealthCare affiliates outside the United
States as Primovist and in Japan as EOB Primovist. It was first approved in
2004 in Europe, and with this FDA approval, is now approved in more than 40
countries.
Clinical Trials Summary
Eight-hundred sixteen (816) patients with suspected or known focal
liver lesions were enrolled in two of four non-randomized,
intrapatient-controlled studies that evaluated predominantly the detection
(Studies one and two) or morphological characterization (Studies three and
four) of liver lesions. Studies one and two ("detection" studies) enrolled
patients who were scheduled for liver surgery. MRI results were compared to
a reference standard that consisted of surgical histopathology and the
results from intra-operative ultrasound of the liver. The studies assessed
the sensitivity of pre-contrast MRI and EOVIST-contrasted MRI for the
detection of liver lesions when each set of images was compared to the
reference.
Studies three and four ("characterization" studies) enrolled patients
with known or suspected focal liver lesions, including patients who were
not scheduled for liver surgery. MRI results were compared to a reference
standard that consisted of surgical histopathology and other prospectively
defined criteria. The studies assessed the correctness of liver lesion
characterization by pre-contrast MRI and EOVIST-contrasted MRI when each
set of images was compared to the reference. Lesions were characterized as
one of the following choices: hepatocellular carcinoma, cholangiocarcinoma,
metastasis, focal lymphoma, adenoma, focal nodular hyperplasia, hemangioma,
abscess, focal liver fibrosis, regenerative nodule, focal fat, hydatid
cyst, liver cyst, "not assessable," normal, no lesion or "other."
In all four studies, patients underwent a baseline, pre-contrast MRI
followed by the administration of EOVIST at a dose of 0.025 mmol/kg body
weight, with MRI performed immediately (the "dynamic" phase) and at 10 to
20 minutes following EOVIST administration (the "hepatocyte" phase).
Patients also underwent computerized tomography with contrast examinations
of the liver. Pre-contrast MRI and EOVIST-contrasted MR images were
evaluated in a systematic, randomized, paired and unpaired fashion by three
radiologists who were blinded to clinical information. Computed tomography
(CT) images were also evaluated by the radiologists in a separate reading
session.
EOVIST was generally well-tolerated during the trials. The safety
database was based on EOVIST exposure in 1,755 adult subjects who received
a dose that ranged from 0.003 to 0.5 mmol/kg body weight; the majority
(N=1,365) received the recommended dose of 0.025 mmol/kg body weight.
Overall, 4.3% of subjects reported one or more drug-related adverse
reactions during a follow-up period that, for most subjects, extended more
than 24 hours after EOVIST administration. These adverse reactions were
predominantly of mild to moderate severity. Serious adverse events were
reported among six patients and were attributed to underlying conditions or
non-MRI procedures. All serious events occurred more than 10 hours
following EOVIST administration. The most common adverse reactions at the
recommended dose were feeling hot, nausea, headache, injection site
reaction (pain, burning, coldness, extravasation), dysgeusia (taste
abnormality), flushing, parosmia (smell abnormality), dizziness and
vomiting.
About EOVIST(R)
EOVIST is the first gadolinium-based, liver-specific MRI contrast agent
approved in the United States. EOVIST enhances the T1-weighted signal.
Compared to other extracellular fluid gadolinium-chelate contrast agents,
EOVIST exhibits a low-level binding to plasma proteins. The resulting
higher relaxivity accounts for the lower dose. The recommended dose of
EOVIST is 0.1 mL/kg body weight (0.025 mmol/kg body weight). Based on its
structural properties, EOVIST is partially taken up by liver cells, thus
enhancing healthy liver tissue (parenchymal enhancement). Lesions with no
or minimal hepatocyte function (e.g., cysts, metastases, the majority of
hepatocellular carcinomas) will remain unenhanced and will therefore be
more readily detected and localized. EOVIST provides useful diagnostic
information at the time immediately after contrast administration (dynamic
imaging) and, thus, also supports lesion characterization (i.e.,
distinction of malignant and benign types of liver lesions). EOVIST is
marketed by Bayer HealthCare affiliates outside the United States as
Primovist(R) and in Japan as EOB Primovist, and is approved in more than 40
countries, including the United States.
WARNING: NEPHROGENIC SYSTEMIC FIBROSIS
Gadolinium-based contrast agents increase the risk of Nephrogenic
Systemic Fibrosis in patients with:
-- acute or chronic severe renal insufficiency (glomerular filtration)
rate