New Blood Pressure Medication Testing To Start Soon
By:Susan M. Pietropaolo, Alteon Inc.
St. Paul, MN, May 16, 2002
The St. Paul Heart Clinic announced that it is recruiting patients for two trials of ALT-711, an investigational drug that has demonstrated a broad beneficial effect in reversing the stiffening of vessels that causes systolic hypertension. The Phase IIb trials are building upon positive data from a Phase IIa human trial that demonstrated ALT-711's ability to increase the elasticity of the vessels, lowering pulse pressure in aging and diabetic patients.
ALT-711, an orally active compound, is being tested in over 630 patients at approximately 60 clinical sites in the United States, including St. Paul Heart Clinic. Recruited patients will receive ALT-711 tablets or placebo once a day for six months, in addition to their existing medications. Patients enrolled in the trials must be 50 years of age or older and have systolic blood pressure (top number) of at least (higher than) 150 mmHg and diastolic blood pressure (bottom number) of less than (lower than) 90 mmHg. Both trials will include male and females, non-diabetic and diabetic patients.
Systolic hypertension is a consequence of the age-related stiffening of the large arteries, and is the most common form of hypertension in people over age 50. Yet it is the type of hypertension least likely to be well treated, according to a study published in the March 16, 2001 edition of Hypertension, a journal of the American Heart Association. No approved drug for high blood pressure directly targets the underlying age-related stiffening that results in systolic hypertension, and thus this condition represents a major unmet medical need.
"Currently available cardiovascular treatments do not directly target vascular stiffening and, as a result, are not optimal for the treatment of systolic hypertension," said Alan Bank, M.D. of St. Paul Heart Clinic, the investigator in this study. "ALT-711 Phase IIa results demonstrated the compound's ability to reverse the stiffening of the arteries that occurs in aging patients, bringing them approximately 30% back to normal. We look forward to the results from these Phase IIb trials, and are pleased to be a part of this important program. ALT-711 may provide a novel approach for a nationwide problem."
An Unmet Medical Need of Aging
Systolic hypertension is the most common form of hypertension in people over age 50, with an estimated prevalence of 15-20 million people in the U.S. alone. Yet it is the type of hypertension least likely to be well treated, according to a recent study published in the March 16, 2001 edition of Hypertension, a journal of the American Heart Association.
Systolic hypertension is a consequence of the age-related stiffening of the large arteries, and it is defined as elevated systolic blood pressure (above 140 mmHg) in conjunction with normal diastolic blood pressure (below 90 mmHg). It is characterized by an increased pulse pressure, defined as the difference between systolic and diastolic blood pressures. The prevalence of hypertension increases with age, with systolic hypertension becoming far more common than diastolic hypertension.
Traditionally, treatment of hypertension has focused on controlling diastolic pressure. Current hypertension therapies, including diuretics, ACE inhibitors, beta blockers, calcium channel blockers and angiotensin receptor blockers have an effect on lowering both systolic and diastolic pressures. Treatment is therefore limited, as a patient may become hypotensive with too low a diastolic pressure.
A recent editorial in The New England Journal of Medicine [August 16, 2001] stated that the control of hypertension is an important national priority, and that clinical practice needs to shift focus to the management of systolic rather than diastolic hypertension. As documented in this issue of the Journal, most cases of uncontrolled hypertension are in persons with elevated systolic blood pressure, particularly in elderly adults. The epidemiological data indicate that systolic blood pressure is significantly more important than diastolic blood pressure as a determinant of cardiovascular risk in this group of patients.
The focus on systolic pressure began to increase in the 1990's with the results from the Systolic Hypertension in the Elderly Program (SHEP) trial and other epidemiological data that demonstrated that the level of systolic blood pressure is a better predictor of cardiovascular events including stroke, coronary heart disease, and heart failure. A systolic blood pressure higher than 160 mmHg has been shown to double all-cause mortality, triple cardiovascular mortality, particularly in women, and more than double cardiovascular morbidity in both sexes. Similarly, elevated pulse pressure is increasingly being recognized as a risk factor for cardiovascular disease. The Framingham Study and others have demonstrated that a reduction in pulse pressure is associated with a significant risk reduction in cardiovascular death.
However, these findings have not yet been reflected in clinical practice, due in part to the fact that there are no approved agents that selectively lower systolic blood pressure. The NEJM editorial states that physicians are often reluctant to treat systolic hypertension for fear of doing harm.
Alteon's proprietary class of A.G.E. Crosslink Breakers, and lead compound ALT-711, may specifically address this treatment issue by directly targeting the stiffening of the arteries that contributes to systolic hypertension. ALT-711 is currently two Phase IIb trials, the SAPPHIRE (Systolic And Pulse Pressure Hemodynamic Improvement by Restoring Elasticity) and SILVER (Systolic Hypertension Interaction with Left VEntricular Remodeling) trials in patients with systolic hypertension, with data expected near year-end 2002.