Contact: Scarlett L. Foster, Monsanto [Financial Inquiries] (314) 694-2883
Kristin R. Fayer, Searle [Product Inquiries)] (847) 470-6728
Leslie Sweeney, Edelman [Product Inquiries] (312) 240-2697
Hypertension, Angina Treated By Verapamil Formulation Delivered by Patented "Controlled-Onset Extended-Release" Technology
FEBRUARY 27, 1996 -- Skokie, IL -- Searle, the pharmaceutical subsidiary of Monsanto Company, announced today that it received U.S. Food and Drug Administration (FDA) approval for Covera-HS (verapamil hydrochloride).
Covera-HS is the first once-daily formulation of an antihypertensive/anti-anginal agent that uses an advanced tablet coating and a novel drug delivery system to mimic the body's typical 24-hour circadian variations in blood pressure and heart rate. This unique delivery technology, called COER-24[TM] (Controlled-Onset Extended-Release), was developed in conjunction with ALZA Corporation.
Covera-HS is the only controlled-release verapamil formulation that is currently approved with an indication for the management of both hypertension (high blood pressure) and angina pectoris (chest pain). Available in both 180 mg and 240 mg tablets, Covera-HS is designed for oral dosing at bedtime. Peak concentration of Covera-HS is delivered in the early waking hours when blood pressure and heart rate are rising at their highest rate. There is minimal drug delivery during sleep when blood pressure and heart rate are at their physiologic lowest.
"Covera-HS represents a significant introduction from our research and development pipeline, which comes at a pivotal time in Searle's long-standing history in cardiovascular medicine. We believe that a once-daily formulation that follows the body's circadian rhythms will offer physicians and their patients an important treatment option that is not completely filled by existing antihypertensive therapies," said Searle Chairman annd Chief Executive Officer Richard U. De Schutter.
Blood pressure and heart rate -- physiologic processes that affect vital cardiovascular functions -- are influenced by these natural, 24-hour circadian rhythm patterns. The science of treating diseases that follow these circadian patterns is known as "chronotherapeutics" and is a well-established practice in medicine for the management of certain medical conditions including asthma, sleep, gastric and peptic ulcer diseases, arthritis and now, hypertension and angina.
According to Michael Smolensky, Ph.D., University of Texas-Houston School of Public Health, "Covera-HS is a major medical advance because this is the first attempt at managing cardiovascular functions in conjunction with the body's circadian variations. The application of new chronotherapeutic treatments may help address the links between variations in body functions and the risk of potential adverse events as outcomes."
COER-24 Delivery System Provides Reliable 24-Hour Coverage
Covera-HS' advanced COER-24 delivery system consists of two stages. First, it provides for a four- to five-hour delay in drug release after bedtime administration. At approximately three hours before awakening, drug release occurs so that peak levels of medication coincide with waking and the first hours of activity. Second, the extended release of drug in the gastrointestinal tract provides 24-hour control of blood pressure and symptoms of angina pectoris.
In two double-blind, randomized, placebo-controlled studies of 382 patients with mild to moderate hypertension, clinically significant 24-hour blood pressure control was demonstrated with once-daily, evening doses of Covera-HS (180 mg/day to 540 mg/day), with peak effects between 6 a.m. and noon.
Angina control with Covera-HS has been evaluated through exercise testing performed in the evening prior to the next day's dose, and in the morning. The drug's efficacy was measured by the period of time before symptom onset in patients with moderate to severe angina. In two, double-blind randomized studies of 453 patients, Covera-HS was shown to extend the duration of exercise before onset of symptoms compared to placebo.
Proven Therapeutics Aligned with Innovative Technology
Covera-HS is a delayed sustained-release version of verapamil hydrochloride, a non-dihydropyridine type compound that is a proven therapeutic agent with a 30-year worldwide history of safety and efficacy in the treatment of hypertension and angina. The innovative technology of the COER-24 delivery system of Covera-HS, which is under patent protection until the year 2011, offers beneficial timing so that the distinct pharmacologic properties of verapamil hydrochloride are enhanced.
The unique features of Covera-HS will be further compared to the first-line "standard-of-care" regimen (diuretic, beta blocker) for hypertension in Searle's $50 million, 15,000-patient, prospective, randomized hypertension study called CONVINCE (Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints). More than 300 institutions worldwide will follow patients for a four- to-six year period to compare Covera-HS with the current standard-of-care therapies, as recommended by the Joint National Committee on the Detection, Evaluation and Treatment of Hypertension (JNC V) in preventing heart attacks, strokes and death.
CONVINCE will also evaluate the ability of Covera-HS and its advanced COER-24 delivery system to effectively reduce the incidence of these adverse cardiovascular events in the early waking, or morning, hours when patients are considered to be at highest risk due to a rapid rise in blood pressure and heart rate.
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Searle, a wholly owned subsidiary of Monsanto Company, is a research-based corporation that develops, manufactures and markets pharmaceutical products and other healthcare solutions worldwide.
ALZA Corporation, headquartered in Palo Alto, CA, is a leader in the development and commercialization of innovative pharmaceutical products using advanced drug delivery technologies to add medical and economical value to drug therapies.
Verapamil should be administered cautiously to patients with impaired renal function. For complete prescribing information for Covera-HS, including contraindications and adverse side effects, please call 1-800-323-4204.
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