Pharmaceutical and life sciences giant Bayer AG scored another indication for its MRI contrast agent, Gadavist (gadobutrol) injection, this time in adults with suspected coronary artery disease. The FDA nod makes Gadavist the first and only contrast agent approved for use in cardiac magnetic resonance (CMR) imaging.
An estimated 16.5 million Americans have coronary artery disease (CAD), and about 370,000 die each year. The condition occurs when the arteries feeding blood, oxygen and nutrients to the heart become damaged or diseased, often as a result of plaque buildup on the artery walls or inflammation. Multiple modalities are used to diagnose CAD, from ultrasound and CT scans to positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scans. Gadavist's approval for CMR gives physicians another tool in the toolbox.
Validated in two clinical trials
The approval was based on two multinational, nonrandomized, blinded-read phase III studies of nearly 1,000 adults with suspected or known CAD, based on signs and symptoms. Nearly 800 patients were evaluated for efficacy. The results showed that, when compared with the gold standard of invasive coronary angiography, CMR has a high accuracy in patients with greater than 70% stenosis of a coronary artery. That is the cut point generally used by cardiologists to indicate the presence of a significant narrowing that would reduce blood flow.
The studies validate what cardiologists have known for years, said Daniel Berman, chief of cardiac imaging and nuclear cardiology at the Cedars-Sinai Heart Institute and the S. Mark Taper Foundation Imaging Center and a large enroller in the one of the trials. "Cardiovascular magnetic resonance perfusion imaging is highly accurate for detecting patients who have too little blood flow potential through their coronaries or ischemia that would be called a stress-induced ischemia," he told BioWorld. "And it has been shown to be similar in accuracy to the other very highly accurate noninvasive study [modality], which is PET scanning."
Having Gadavist as an approved MR contrast agent "allows us to use what was already being widely used off-label, and that should allow a broader dissemination of CMR perfusion studies in the [cardiology] community," he added.
Berman pointed to another study published June 20 in The New England Journal of Medicine that compares rest-and-stress MR perfusion studies with a fractional flow reserve, a technique used in coronary catheterization to measure pressure differences across a coronary artery stenosis. The procedure is used to assess the likelihood that stenosis is hindering oxygen supply to the heart and identify patients who might benefit from revascularization. In the multicenter MR-INFORM study, patients randomized to MRI underwent fewer revascularizations, yet had similar outcomes to the fractional flow reserve group.
The study provides further evidence that MRI is "an accurate tool for detecting significant coronary artery disease that might need intervention with angioplasty or bypass surgery, and one that appears to be equally effective to an approach using fractional flow reserve," Berman said.
"It's an exciting time for us," Dennis Durmis, senior vice president and head of the Americas region at Bayer Radiology, told BioWorld. "Being able to provide another diagnostic tool for physicians to use to look for the disease and understand what treatment paths could be appropriate for patients is critical."
CAD is one of the larger disease areas for which Gadavist is indicated and, as such, could translate to a sizeable new market for the drug. Last year, Bayer reported global sales of €366 million (US$410.6 million) from Gadavist applications in the brain, spine, breast, liver and kidneys.
"We would expect that in the MR environment, we would be looking at a couple of percentage points of growth year over year as a result of the indication and the ability for physicians to now leverage Gadavist for those [CMR] procedures," Durmis said.
Fourth U.S. indication
Gadavist was first approved in the U.S. in 2011 for intravenous MR imaging of adults and children ages 2 and older to detect and visualize areas with disrupted blood-brain barrier or abnormal vascularity of the central nervous system (CNS). That was followed by FDA approvals in 2014 to assess breast malignancies and for the CNS indication in children younger than 2. In 2016, Bayer won a further U.S. indication for Gadavist with magnetic resonance angiography to assess known or suspected supra-aortic or renal artery disease in adults and children, including full-term neonates.
The new CMR approval underscores the importance of investing in multiple indications for contrast agency, as each indication contributes to diagnostic information available for doctors, imagers and patients.
"There are plenty of markets that provide whole body indications. The FDA made a choice not to go there, and so, in order for radiologists to use the product on label, we needed to continue to invest in that space," Durmis said. "This is the largest one we've done in the last seven or eight years, and it is part of our ongoing strategy." He said Bayer is spending "tens of millions a year in the contrast media space" and will continue to invest heavily to expand indications or develop new agents.