CV Therapeutics, Inc. and Astellas Pharma US, Inc. announced that CV Therapeutics has submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) seeking approval of regadenoson for use in myocardial perfusion imaging (MPI) studies. The NDA submission triggers a $7 million milestone payment from Astellas to CV Therapeutics.
Regadenoson is a selective A2A-adenosine receptor agonist under development for use as a pharmacologic stress agent in MPI studies. Regadenoson has been designed to be delivered as a rapid bolus with no dose adjustment required by weight, and to selectively stimulate the A2A-adenosine receptor, the receptor responsible for coronary vasodilation.
"We are very pleased to have submitted an NDA for regadenoson, which, if approved in 2008, would represent the second innovative cardiovascular product CV Therapeutics will have brought to market in a two year period," said Louis G. Lange, M.D., Ph.D., chairman and chief executive officer of CV Therapeutics.
"As the market leader in pharmacologic stress testing, we look forward to the market introduction of regadenoson. We are seeing a continued increase in demand for myocardial perfusion imaging tests in the United States and, upon approval, we believe both patients and physicians will benefit from the clinical profile of regadenoson," said Yoshihiko Hatanaka, president and chief executive officer of Astellas Pharma US, Inc.
If regadenoson is approved by the FDA, Astellas Pharma US, Inc. will be responsible for all commercial activities for regadenoson in the United States. CV Therapeutics retains all rights to regadenoson outside of North America.
The NDA contains data from two identically designed Phase 3 clinical trials. In both Phase 3 trials, regadenoson met the primary endpoint by showing with 95 percent confidence that MPI studies conducted with regadenoson were comparable to MPI studies conducted with Adenoscan (adenosine injection).
Regadenoson was generally well tolerated in both Phase 3 studies. The most common adverse events reported in patients who received regadenoson were shortness of breath, headache, flushing, chest discomfort and dizziness.
Patients 18 years or older with the clinical need for an MPI study were eligible to participate in the Phase 3 clinical trials. Individuals who had an acute myocardial infarction or unstable angina within three months, or coronary revascularization within six months, were not permitted to participate in the study.
All study participants received a clinically indicated baseline MPI study using Adenoscan (adenosine injection). Participants then were randomized to receive either regadenoson or Adenoscan (adenosine injection) in a double blinded fashion during a second MPI study. Each patient's scans were classified as indicating normal, moderate or severe ischemia. Baseline and blinded scans then were evaluated to determine if the scans were comparable.
Under a license and collaboration agreement providing Astellas with exclusive North American rights to regadenoson, CV Therapeutics manages the development program and Astellas is responsible for all commercial activities for regadenoson in North America, if the product is approved for marketing. Under the arrangement, Astellas owes CV Therapeutics a $7 million milestone upon NDA submission and a $12 million milestone upon FDA approval, and reimburses CV Therapeutics for 75 per cent of development costs. CV Therapeutics will receive a royalty on product sales of regadenoson, if approved, and may receive a royalty on another product. CV Therapeutics owns the rights for regadenoson outside of North America.