POZEN Inc. (NASDAQ: POZN), a pharmaceutical company committed to transforming medicine that transforms lives, today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the marketing approval of PA32540/PA8140. Both products are a coordinated-delivery tablet combining immediate-release omeprazole (40 mg), a proton pump inhibitor (PPI), layered around a pH-sensitive coating of an aspirin core. Pending regulatory approval, an indication is sought for the use of PA tablets for the secondary prevention of cardiovascular disease in patients at risk for aspirin-induced ulcers. “The NDA submission for PA32540/PA8140 represents an important milestone for PA,” said John R. Plachetka, Pharm.D., Chairman, President and Chief Executive Officer of POZEN. “Although this PA NDA is focused on patients who need the beneficial lifesaving cardiovascular properties of aspirin but are at risk for developing gastric ulcers, it is our hope that sometime in the future additional research will confirm the promise of aspirin as an important drug in the war against cancer, and perhaps other diseases. In discussions with potential partners, we believe we have seen the same commitment from them to transform the benefit/risk profile of aspirin that has driven our team at POZEN over the past several years. We look forward to completing a commercial deal in the upcoming months with a partner that shares our passion for this product, our values, and is capable of making PA reach its fullest potential in the marketplace.” The NDA submission is based on data from a comprehensive clinical trials program that POZEN conducted. This program included two pivotal Phase 3 studies (PA32540 – 301/PA32540 – 302) for PA32540, conducted under special protocol assessment (SPA) agreed with the FDA, which met their primary and secondary endpoints, as well as extensive Phase 1 studies for both PA32540 and PA8140. In the 301 and 302 studies, significantly fewer subjects taking PA32540 experienced endoscopically confirmed gastric ulcers compared to subjects receiving enteric-coated (EC) aspirin alone (Study 301: 3.8% vs. 8.7%, p=0.02; Study 302: 2.7% vs. 8.5%, p=0.005, respectively).
About Cardiovascular DiseasePatients 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 in the United States. Every 25 seconds, someone in the United States will suffer a coronary event. About every minute, someone will die from one. 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. The American College of Cardiology with the AHA issued a Clinical Expert Consensus in 2008 recommending PPIs as preferred agents for the therapy and prophylaxis of aspirin-associated gastrointestinal injury.
About the Phase 3 StudiesThe 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% respectively, 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). About PA POZEN is creating a portfolio of integrated aspirin therapies - the PA product platform. The products in the PA portfolio are intended to significantly reduce gastrointestinal (GI) ulcers and other GI complications compared to taking enteric-coated or plain aspirin alone.
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 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 ulcers.About POZEN POZEN Inc. is a small pharmaceutical company that specializes in developing novel therapeutics for unmet medical needs and licensing those products to other pharmaceutical companies for commercialization. By utilizing a unique in-source model and focusing on integrated therapies, POZEN has successfully developed and obtained FDA approval of two self-invented products in two years. Funded by these milestones/royalty streams, POZEN is creating a portfolio of cost-effective, evidence-based integrated aspirin therapies designed to enable the full power of aspirin by reducing its GI damage. POZEN is currently seeking strategic partners to help maximize the opportunities for its portfolio assets. The Company's common stock is traded under the symbol “POZN” on The NASDAQ Global Market. For more detailed company information, including copies of this and other press releases, please visit www.pozen.com. Forward-Looking Statements 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 POZEN sponsored market studies and reports), management’s current expectations and are subject to a number of risks and uncertainties, including, but not limited to, our inability to license our PA product candidates on terms and timing acceptable to us, our inability to file a new drug application with the FDA for our PA product candidates in the timeframe we anticipate, our failure to successfully commercialize our product candidates; costs and delays in the development and/or FDA approval of our product candidates, including as a result of the need to conduct additional studies, or the failure to obtain such approval of our product candidates, including as a result of changes in regulatory standards or the regulatory environment during the development period of any of our product candidates; uncertainties in clinical trial results or the timing of such trials, resulting in, among other things, an extension in the period over which we recognize deferred revenue or our failure to achieve milestones that would have provided us with revenue; our inability to maintain or enter into, and the risks resulting from our dependence upon, collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing, sales and distribution of any products, including our dependence on AstraZeneca for the sales and marketing of VIMOVO ® ; competitive factors; our inability to protect our patents or proprietary rights and obtain necessary rights to third party patents and intellectual property to operate our business; our inability to operate our business without infringing the patents and proprietary rights of others; general economic conditions; the failure of any products to gain market acceptance; our inability to obtain any additional required financing; technological changes; government regulation; changes in industry practice; and one-time events, including those discussed herein and in our Annual Report on Form 10-K for the period ended December 31, 2012. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements.