Presence of Gastric Erosions in Patients Taking Low-Dose Aspirin for Secondary Cardiovascular Preven
May 21st 2013 7:43AM
Updated May 21st 2013 8:35AM
Presence of Gastric Erosions in Patients Taking Low-Dose Aspirin for Secondary Cardiovascular Prevention May Result in a 2-Fold Increase in Future Gastric Ulcers
Results of a PA32540 Phase 3 Post-Hoc Analysis Presented at DDW 2013 Also Revealed That Over 4% of These Patients May Have Gastric Ulcers Without Knowing It
CHAPEL HILL, N.C.--(BUSINESS WIRE)-- POZEN Inc.
In patients with gastric erosions at baseline, PA32540, a coordinated-delivery tablet combining immediate-release omeprazole (40 mg), layered around a pH-sensitive coating of a 325 mg ASA core, resulted in significantly fewer gastric ulcers at six months vs. EC-ASA (325 mg) (4.2% vs. 13.0%; p=0.001) These data were presented for the first time at Digestive Disease Week (DDW) 2013 in Orlando, Florida at the Orange County Convention Center on May 20,2013.
"These study findings better define the gastromucosal protective effects of PA32540 in patients with underlying cardiovascular disease," said Jay L. Goldstein, M.D., Chief of Gastroenterology, Northshore University Health System. "Identifying and appropriately managing cardiovascular patients who are at risk for gastric ulcers is an important therapeutic and safety goal. Known risk factors for upper gastrointestinal complications include age and previous peptic ulcer disease, amongst others. Patients on long-term aspirin should be regularly questioned about UGI symptoms that may impact long-term adherence to aspirin."
Key Findings of Post-Hoc Analysis
- The baseline rate of gastric ulcers in the screening of the general population of adults using ASA (325 mg) for ≥3 months for secondary cardiovascular prevention was 4.4%, and was 5.7% for both gastric or duodenal ulcers.
- In the post-hoc analysis of subjects with and without gastric erosion at baseline endoscopy, the presence of gastric erosion at baseline was:
- Predictive of a higher rate of subsequent gastric erosions for both EC-ASA (325 mg) and PA32540.
- Associated with a significant propensity toward future gastric ulcer development in subjects treated with EC-ASA (325 mg), but not in those treated with PA32540.
- In patients with baseline gastric erosions, a significantly higher percentage of patients taking EC-ASA (325 mg) developed a gastric ulcer over the six month study period than patients taking PA32540 (13% vs. 4.2%; p=0.001).
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).
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 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.
POZEN is creating a portfolio of integrated aspirin therapies - the PA product platform. The products in the PA portfolio are intended to significantly reduce 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 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.
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 now 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.
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 Quarterly Report on Form 10-Q for the period ended March 31, 2013. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements.
Bill Hodges, 919-913-1030
Chief Financial Officer
Stephanie Bonestell, 919-913-1030
Manager, Investor Relations & Public Relations
KEYWORDS: United States North America North Carolina
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