TARRYTOWN, N.Y., Nov. 7 /PRNewswire-FirstCall/ -- Emisphere Technologies, Inc. today announced that it has received written guidance from the U.S. Food and Drug Administration (the “FDA”) regarding the Company’s planned Phase III trial with oral heparin. The planned trial is designed to determine the safety and efficacy of oral heparin versus titrated Coumadin(R) (sodium warfarin) for the prevention of venous thromboembolism (“VTE”) following elective total hip replacement.
The trial will be a randomized double blind, non-inferiority, multi-center study with the primary endpoint to prevent VTE, which consists of deep venous thrombosis (“DVT”), objectively confirmed by ultrasound, pulmonary embolism and death. The two arm study will compare 30 days of dosing, three times per day, of two Emisphere oral heparin capsules, to 30 days of dosing, once per day, of oral titrated Coumadin(R). The expected enrollment for the trial is approximately 2100 patients (including an allowance for non-evaluable patients), with 1050 patients per arm. An independent Data and Safety Monitoring Committee (“DSMC”) will be charged with periodically reviewing the trial for safety. Emisphere plans to initiate the study in the first half of 2006.
“We believe we have made important progress with the FDA in terms of defining a Phase III clinical strategy with our oral heparin program. Based on discussions and correspondence with the FDA over the past year, we are confident that our trial design will assist us in demonstrating the safety and efficacy of our oral heparin product. Our trial design incorporates the use of ultrasound as the primary event detection technique, which should enable rapid enrollment in the trial at high quality U.S. clinical sites,” said Michael M. Goldberg, M.D., Chairman and Chief Executive Officer. “We have worked with our Steering Committee on the trial design and the members of that committee - Samuel Z. Goldhaber, MD, Cardiovascular Division, Brigham and Women’s Hospital; Professor Ajay Kakkar, BSc, MBBS (Hons), PhD, FRCS, Institute of Cancer, Barts, The London School of Medicine, and Professor Russel D. Hull, MBBS, MSc, FRCPC, University of Calgary - will remain closely involved with us throughout the trial.”
“Also, we have been working with the FDA to demonstrate our belief that heparin, when given orally using our technology, is unaltered as compared to heparin delivered by injection. Those results will be available shortly. Once available, we will discuss the data with the FDA to determine if these data can accelerate our product registration. In addition, we intend to pursue a Special Protocol Assessment with the FDA for the Phase III trial, further decreasing the regulatory and clinical development risk associated with late stage drug development,” Goldberg concluded.
Dr. Goldhaber remarked: “Prevention and treatment of VTE will be well served by the introduction of a safe and effective, fixed dose, oral agent, and I am delighted to be working with Emisphere on this study.”
Patients undergoing hip replacement surgery are treated prophylactically with heparin, low molecular weight heparin, pneumatic compression devices in combination with aspirin, or oral anticoagulants like Coumadin(R). Warfarin is used by many physicians as it is the only approved oral agent in the U.S. for the indication of DVT prophylaxis. Various injected heparins are also used by many physicians due to their fixed dose, no monitoring dosing regimen. We believe that there is an unmet medical need for a safe and effective fixed- dose, oral anticoagulant that can be administered without monitoring and that, therefore, such an anticoagulant would be clinically beneficial, patient friendly and potentially cost-effective.
Currently, heparin is not administered orally because it is not absorbed from the gastrointestinal tract due to its size, poor lipid solubility, and ionic repulsion from the negatively charged epithelial tissue. Emisphere’s proprietary compound Sodium N-[8(-2-hydroxybenzoy l) amino] caprylate (SNAC) is a delivery agent that can be combined with heparin to mediate its gastrointestinal absorption by a passive transcellular process, without apparent damage to intestinal epithelium.
About Deep Vein Thrombosis
Deep vein thrombosis is a condition in which a blood clot (thrombus) develops in deep veins of the body, most often in the deep veins of the legs, either above the knee or below it. While this condition itself is not life- threatening, the blood clot can break free (called emboli) and become lodged in the blood vessels of the lung causing pulmonary embolism.
Thromboembolic events kill more people in the U.S. than AIDS, breast cancer, and highway fatalities combined. Every year, approximately 2 million Americans are affected by deep vein thrombosis, and approximately 600,000 experience pulmonary embolisms. For up to 200,000 of those with PE, the blood clot in the lung proves fatal. Approximately 600,000 people with DVT are hospitalized and about 60,000 die each year in the U.S. as a result of VTE.
There are approximately 350,000 patients who undergo total hip replacement surgery in the U.S. each year. In addition, anticoagulant therapy is prescribed for total knee replacement (estimates are U.S. 350,000 patients), DVT treatment (estimates are U.S. 600,000 patients), atrial fibrillation (estimates are U.S. 1.5 million patients), and a number of other indications. The prevalence of DVT and PE in knee and hip replacement patients has been well documented. Patients who undergo total hip replacement are at a high risk of developing VTE which includes DVT and PE.
About Emisphere Technologies, Inc.
Emisphere Technologies, Inc. is a biopharmaceutical company pioneering the oral delivery of otherwise injectable drugs. Emisphere’s business strategy is to develop oral forms of injectable drugs, either alone or with corporate partners, by applying its proprietary eligen(R) technology to those drugs or licensing its eligen(R) technology to partners who typically apply it directly to their marketed drugs. Emisphere’s eligen(R) technology has enabled the oral delivery of proteins, peptides, macromolecules and charged organics. Emisphere and its partners have advanced oral formulations or prototypes of salmon calcitonin, heparin, insulin, parathyroid hormone, human growth hormone and cromolyn sodium into clinical trials. Emisphere has strategic alliances with world-leading pharmaceutical companies. For further information, please visit http://www.emisphere.com.
Safe Harbor Statement Regarding Forward-looking Statements
The statements in this release and oral statements made by representatives of Emisphere relating to matters that are not historical facts (including without limitation those regarding the timing or potential outcomes of research collaborations or clinical trials, any market that might develop for any of Emisphere’s product candidates and the sufficiency of Emisphere’s cash and other capital resources) are forward-looking statements that involve risks and uncertainties, including, but not limited to, the likelihood that future research will prove successful, the likelihood that any product in the research pipeline will receive regulatory approval in the United States or abroad, the ability of Emisphere and/or its partners to develop, manufacture and commercialize products using Emisphere’s drug delivery technology, Emisphere’s ability to fund such efforts with or without partners, and other risks and uncertainties detailed in Emisphere’s filings with the Securities and Exchange Commission, including those factors discussed under the caption “Risk Factors” in Emisphere’s Annual Report on Form 10-K (file no. 1-10615) filed on March 29, 2004.
Emisphere Technologies, Inc.
CONTACT: Gillian Racine, Investor Relations of Emisphere Technologies,Inc., +1-914-785-4742; or Media, Dan Budwick of BMC Communications forEmisphere Technologies, Inc., +1-212-477-9007 ext. 14
Web site: http://www.emisphere.com//
