King Pharmaceuticals Announces Submission Of New Drug Application For CorVue™

Main Category: Cardiovascular / Cardiology
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 27 Dec 2008 - 1:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

King Pharmaceuticals, Inc. (NYSE: KG) announced it has submitted a New Drug Application (NDA) for CorVue™ (binodenoson) for injection to the U.S. Food and Drug Administration (FDA). CorVue™ is a cardiac pharmacologic stress SPECT (single-photon-emission computed tomographic) imaging agent intended for use in patients with or at risk for coronary artery disease (CAD) who are unable to perform a cardiac exercise stress test.

In the NDA, King is requesting FDA approval of CorVue™ as an adjunct to non-invasive myocardial perfusion imaging (MPI) tests to detect perfusion abnormalities in patients with known or suspected CAD. The NDA includes two Phase III clinical studies that compared CorVue™, a coronary vasodilator that is a selective agonist at the adenosine A2A receptor subtype, to adenosine, a current agent of choice for pharmacologic stress testing. The studies showed that CorVue™ achieved the primary endpoints for efficacy and tolerability, and has an improved side effect profile compared to adenosine.

"Use of currently available agents for pharmacologic cardiac stress testing may be limited by side effects. Unlike some of these agents, CorVue™ targets a singular adenosine receptor subtype. As a result, CorVue™ was shown to produce fewer and less severe side effects than adenosine, including the risk of AV heart block, a rare but potentially serious side effect associated with adenosine-based agents," said Dr. Eric Carter, Chief Science Officer of King. "We are confident that, if approved, CorVue™ will provide physicians and patients with a safe and effective option to diagnose a disease that affects about one in three adults and is the leading cause of death in the U.S."

Vasodilator pharmacologic stress agents work by stimulating adenosine receptors in the coronary vasculature (the network of blood vessels in the heart). Of the four adenosine receptor subtypes - A1, A2A, A2B, and A3 - only the A2A receptor appears to promote coronary vasodilation; stimulation of the other three receptor subtypes may cause side effects, such as shortness of breath, chest pain, nausea and flushing (redness of the skin coupled with warming or burning on the face and neck). CorVue™ targets the A2A receptor, a relative specificity that may result in fewer side effects. In contrast, adenosine stimulates all four adenosine receptor subtypes.

In patients with ischemia (insufficient blood supply to the heart resulting from narrowed or blocked coronary arteries), physicians often use MPI stress testing to view blood flow throughout the heart. For the tests to yield the best possible images, blood flow needs to be significantly increased - usually accomplished through exercise on a treadmill - prior to the injection of an imaging agent. However, as many as 40% of patients cannot perform the level of exercise typically required for disease diagnosis in a cardiac stress test, either due to physical limitations or underlying cardiac or pulmonary disease. For these patients - representing an estimated 4.3 million procedures annually - vasodilator pharmacological stress agents can be used to dilate the blood vessels and increase blood flow to allow physicians to accurately detect the presence and severity of CAD.

About the NDA

The NDA for CorVue™ is based on two Phase III, randomized, multicenter, double-blind, crossover trials (VISION-302 and -305) that compared CorVue™ to adenosine for efficacy, safety and tolerability. King selected this analytical approach to provide the most robust and clinically relevant measure of efficacy between CorVue™ and adenosine. In addition, the crossover design provided the most rigorous comparison of the safety of CorVue™ and adenosine among the same patients.

In the studies, a total of 852 patients in 39 U.S. sites were referred for pharmacologic stress tests and SPECT imaging for myocardial perfusion (MP). Patients completed two double-blinded MP procedures within seven days in random order. In one procedure, patients received an IV bolus of CorVue™ (1.5 mcg/kg) plus a six-minute placebo infusion matching adenosine. In the other procedure, patients received an IV bolus placebo matching CorVue™ plus the clinically indicated six-minute adenosine infusion. A cohort of 138 patients in one study completed two double-blinded adenosine procedures. Blinded readers independently scored rest-stress images.

The efficacy analyses were based on comparison of the extent and severity of myocardial ischemia detected by the CorVue™ and adenosine images in the same patients. The results showed that the images acquired with CorVue™ were equivalent to those acquired with adenosine. In the safety analyses of both studies, no patient experienced 2nd- or 3rd-degree atrioventricular (AV) block after dosing with CorVue™, whereas 3% and 1% of the same patients experienced 2nd- or 3rd-degree AV block following adenosine (p≤0.04). In both studies, the frequency and intensity of chest pain, dyspnea and flushing were significantly lower with CorVue™ compared with adenosine. The frequency and intensity of nausea were significantly lower in one study. Both agents produced comparable changes in blood pressure and heart rate.

About Coronary Artery Disease

Coronary artery disease (CAD) is a condition in which plaque builds up inside the coronary arteries, thereby narrowing or blocking the arteries and reducing blood flow to the heart. CAD is one of the most common forms of cardiovascular disease and is the leading cause of death globally. In the United States, it is estimated that CAD affects 16 million adults and kills more than 450,000 people annually - about one out of every five deaths.

About CorVue™

CorVue™, a selective adenosine A2A receptor agonist, is being developed as an alternative to exercise prior to cardiac perfusion imaging for the diagnosis of coronary artery disease. CorVue™ is designed to minimize side effects such as dyspnea, flushing, heart block, and chest pain. For ease of administration, CorVue™ is being developed for dosing as a single IV injection. CorVue™ has a fast onset while providing a sufficient duration of coronary blood vessel dilation for flexibility in diagnostic imaging.

About King Pharmaceuticals

King, headquartered in Bristol, Tennessee, is a vertically integrated branded pharmaceutical company. King, an S&P 500 Index company, seeks to capitalize on opportunities in the pharmaceutical industry through the development, including through in-licensing arrangements and acquisitions, of novel branded prescription pharmaceutical products and technologies that complement the Company's focus in specialty-driven markets, particularly neuroscience, hospital and acute care. King strives to be a leader and partner of choice in bringing innovative, clinically-differentiated medicines and technologies to market.

http://www.kingpharm.com

Forward-looking Statements

This release contains forward-looking statements which reflect management's current views of future events and operations, including, but not limited to, statements pertaining to the potential benefits of CorVue™ if approved. These forward-looking statements involve certain significant risks and uncertainties, and actual results may differ materially from the forward-looking statements. Some important factors which may cause actual results to differ materially from the forward-looking statements include dependence on the unpredictability of the duration and results of the FDA's review of the CorVue™ NDA. Other important factors that may cause actual results to differ materially from the forward-looking statements are discussed in the "Risk Factors" section and other sections of King's Form 10-K for the year ended December 31, 2007 and Form 10-Q for the quarter ended September 30, 2008, which are on file with the U.S. Securities and Exchange Commission ("SEC"). King does not undertake to publicly update or revise any of its forward-looking statements even if experience or future changes show that the indicated results or events will not be realized.

King Pharmaceuticals