|POZEN Announces FDA Acceptance of Filing of New Drug Application for PA32540/PA8140 Tablets|
The NDA submission is based on data from a comprehensive clinical trials
Aspirin therapy has become the standard of care for reducing an
individual’s risk of a second heart attack or stroke. Studies have found
that a daily aspirin regimen for people who have experienced a previous
heart attack reduces the risk of a second heart attack by about
one-third. Aspirin has been incorporated into the American Heart
Association’s (AHA) clinical guidelines for the secondary prevention of
cardiovascular events. In accordance with these guidelines,
approximately 24 million Americans should be taking aspirin for
secondary prevention of cardiovascular events. Although the
cardiovascular disease (CVD) benefits of aspirin are well established,
the use of aspirin is associated with the risk of upper gastrointestinal
bleeding (UGIB). The use of aspirin is associated with a 2- to 4- fold
increased risk of UGIB. In addition, aspirin use for CVD is an important
cause of gastrointestinal bleeding-related death. The use of the proton
pump inhibitors, such as omeprazole can significantly reduce the risk of
upper gastrointestinal bleeding.
About the Phase 3 Studies
The two Phase 3, double-blind, randomized, multicenter studies enrolled 1,049 subjects who had been prescribed daily aspirin (325 mg) for greater than or equal to three months for secondary prevention of cardiovascular events. The primary endpoint was the cumulative observed incidence of gastric ulcers over six months. Secondary endpoints included cumulative incidence of gastric and duodenal ulcers, discontinuation due to pre-specified upper gastrointestinal (UGI) adverse events and heartburn resolution.
Subjects were randomly assigned to once-daily treatment with PA32540 or 325 mg of enteric-coated aspirin. Endoscopic assessments were performed at screening and at one, three and six months. Major adverse cardiac events (MACE) were reviewed and adjudicated by an independent, blinded endpoint committee composed of Cardiologists.
Each study achieved its individual primary endpoint, and also met all secondary endpoints. Results from the combined data from the two studies demonstrated that patients on PA32540, compared to those on enteric-coated aspirin (325 mg), were able to stay on therapy longer due to fewer discontinuations due to any adverse events (6.7% vs. 11.2%). Discontinuations due to pre-specified UGI events were lower in subjects taking PA32540 compared to subjects taking enteric-coated aspirin (1.5% vs. 8.2%, p<0.001).
In the combined data from the two trials, 85.1% of subjects on enteric-coated aspirin (325 mg) reported adverse events compared to 71.8% of subjects on PA32540. The most commonly reported adverse events with PA32540 and enteric-coated aspirin (325 mg) were of the GI tract and include dyspepsia (11.3% vs. 30.2%), erosive gastritis (11.5% vs. 26.3%), and gastritis (17.5% vs. 16.0%), respectively. The incidence and nature of adjudicated MACE such as heart attacks was similar between the two treatment arms: 9 subjects (1.7%) on PA32540 experienced adjudicated MACE compared to 13 subjects (2.5%) on aspirin (325 mg).
The first candidates are PA32540, containing 325 mg of aspirin, and PA8140, containing 81 mg of aspirin. Both products are a coordinated-delivery tablet combining immediate-release omeprazole (40 mg), a proton pump inhibitor, layered around a pH-sensitive coating of an aspirin core. This novel, patented product is administered orally once a day and an indication will be sought for use for the secondary prevention of cardiovascular disease in patients at risk for aspirin-induced gastric ulcers.
Proposed PA Indications and Usage
PA8140/PA32540 Tablets contain 81 mg or 325 mg delayed release aspirin and 40 mg immediate-release omeprazole and are indicated for patients who require aspirin (1) to reduce the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli, (2) to reduce the combined risk of death and nonfatal MI in patients with a previous MI or unstable angina pectoris, (3) to reduce the combined risk of MI and sudden death in patients with chronic stable angina pectoris, (4) in patients who have undergone revascularization procedures (CABG, PTCA) when there is a pre-existing condition for which aspirin is already indicated, and to decrease the risk of developing gastric ulcers in patients at risk for developing aspirin-associated gastric ulcers.
Controlled studies with PA8140/PA32540 Tablets do not extend beyond 6 months.
About Cardiovascular Disease
Patients with established coronary heart disease or cerebrovascular
disease have a high risk of a subsequent cardiovascular event including
myocardial infarction (MI), stroke and death from cardiovascular
disease. For such patients, lifestyle changes and drug therapy are of
proven benefit and will improve outcomes. Coronary artery disease is
caused by atherosclerosis and often develops into angina pectoris and
MI. The condition caused about 445,000 deaths in 2005 and remains the
leading single cause of death in America today. Roughly 16.8 million
people have a history of MI and/or angina. An estimated 24 million have
been identified as secondary prevention patients (post-event). It is
estimated that cardiovascular disease causes one in every three deaths
The Company's common stock is traded under the symbol “POZN” on The
Statements included in this press release that are not historical in
nature are “forward-looking statements” within the meaning of the “safe
harbor” provisions of the Private Securities Litigation Reform Act of
1995. You should be aware that our actual results could differ
materially from those contained in the forward-looking statements, which
are based on current market data and research (including third party and