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Clinical Development - Veletri™ |
THE ACTELION ANNUAL REPORT 2003 |
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| Clinical Development - Veletri™ |
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| Veletri™ in Acute Heart Failure |
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Acute heart failure (AHF) is the leading cause of emergency admission to hospitals, affecting approximately 2 million patients per year. Although current treatments can ameliorate the symptoms, none of these therapies have been shown to improve mortality and morbidity. Veletri™ (tezosentan) is a potent intravenous dual endothelin antagonist that has been shown in previous trials to improve cardiac hemodynamics.
In 2001, Actelion evaluated Veletri™ in AHF for the first time with the RITZ-1 and RITZ-2 (Randomized Intravenous TeZosentan) studies. Although RITZ-2 showed that Veletri™ improves cardiac hemodynamics in AHF patients, both studies were concluded unsuccessfully because treatment with 50 and 100 mg/h was associated with excess dose-related vasodilatory adverse events, which could have masked clinical benefit. In 2002, a dose-optimization study confirmed the clinical benefit of Veletri™ in AHF and defined the best dosing regimen (5mg/h for a short period followed by 1mg/h) with minor vasodilatory side effects. The results of the dose optimization trial showed improvements in important hemodynamic parameters such as cardiac index (CI) and pulmonary capillary wedge pressure (PCWP). These improvements were not associated with clinically relevant side effects.
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In late 2003, Actelion initiated trials to evaluate Veletri™ in improving clinical endpoints in patients with AHF, which is known as the VERITAS program (Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study). Two similar Phase III trials, VERITAS 1 and VERITAS 2, were initiated using doses identified in the dose optimization trial. A total of 1,760 patients are expected to participate, making it the largest clinical trial in this indication. Results are expected in early 2005.
In addition, Veletri™ is being evaluated in a complication of liver cirrhosis known as hepatorenal syndrome (HRS), a disease in which functional vasospasm leads to renal failure and death. HRS is usually not responsive to standard vasodilators. Endothelin is thought to play a major role in this intense vasoconstriction within the kidney. Two exploratory Phase II studies, one in HRS and the other in patients with cirrhosis who have severe portal hypertension, have been initiated. The study in HRS evaluates the renal dynamic response to an infusion of Veletri™. The study in portal hypertension assesses the effects of an infusion of Veletri™ on the pressure within the portal vein. Results are expected in the second quarter of 2004.
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