Scios Announces Results of ASCEND Heart Failure Study at the Scientific Sessions of the American Heart Association

Study Provides Valuable Safety Information; Demonstrates No Additional Efficacy Beyond Existing Label

Chicago, -- Scios Inc. announced today that the landmark investigational study of NATRECOR® (nesiritide) for the treatment of acutely decompensated heart failure (ADHF), ASCEND-HF, demonstrated no statistically significant difference from placebo in the co-primary endpoints of dyspnea, measured at six and 24 hours, or in the composite of heart failure re-hospitalizations and death during the first 30 days following treatment. Importantly, the study reinforced the safety profile of NATRECOR®, revealing no excess adverse effects on renal function or mortality.

NATRECOR® is approved for use by the U.S. Food and Drug Administration (FDA) for the treatment of patients with acutely decompensated heart failure who experience dyspnea (shortness of breath) at rest or with minimal activity with proven efficacy impact at three hours.1 Scios initiated the 7,141 patient ASCEND-HF study (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) in 2007 after first seeking the guidance of an expert panel of cardiology and heart failure clinicians chaired by Eugene Braunwald, M.D., Harvard Medical School, in response to questions raised in the medical literature about mortality and impaired renal function of patients treated with NATRECOR®.

“The ASCEND-HF trial has answered many scientific questions and has increased our understanding of the safety profile of NATRECOR®,” said Peter M. DiBattiste, M.D., Vice President of Cardiovascular Development at Johnson & Johnson Pharmaceutical Research and Development, L.L.C. “This is the largest trial ever conducted in patients with ADHF, and affirms our commitment to patients and physicians who have limited treatment options to fight this life threatening disorder.”

The results from ASCEND-HF will be submitted to the FDA as part of the standard collection of post-marketing drug experience.

Adrian F. Hernandez, M.D. MHS, Associate Professor, Duke Clinical Research Institute, presented the results during a late-breaking clinical trial presentation during the Scientific Sessions of the American Heart Association.


Review of Clinical Trial Results
In ASCEND-HF, NATRECOR® did not show a statistically significant reduction in either of the composite co-primary endpoint measures: reduction of re-hospitalization due to heart failure or all-cause mortality during the first 30 days following treatment compared to placebo plus standard of care, (9.4% vs. 10.1%, respectively, p=0.313), or a reduction of heart failure symptoms as measured by subject self-assessment on a dyspnea scale at six and 24 hours after initiation, (p=0.030 at 6 hours and p=0.007 at 24 hours).

Safety measures from ASCEND-HF showed that patients treated with NATRECOR® plus standard care had a comparable mortality rate to patients treated with placebo plus standard of care at 30 days (3.6% vs. 4.0%, p=NS). Furthermore, there was no statistically significant or clinically relevant evidence of kidney function impairment in NATRECOR®-treated patients with ADHF during the first 30 days based on a 25% decrease in glomerular filtration rate (31.4% vs. 29.5%, p=NS). Incidence of a known side effect, hypotension (a decrease in blood pressure), was statistically significantly increased with the use of NATRECOR® compared to placebo (26.6% vs. 15.3%); however, the majority of these episodes were asymptomatic.


About ADHF
An estimated 5.7 million people around the globe are diagnosed with heart failure each year, and for most causes there is no known cure.2 The condition can worsen over time, or decompensate, to the point where hospitalization is required, a change that physicians refer to as ADHF. Symptoms and signs of ADHF include extreme fatigue and shortness of breath, worsening kidney function, severe swelling, sudden weight gain and a distended jugular vein along the side of the neck.3 It is the leading cause of hospitalization in Americans over age 65.4


About NATRECOR® (nesiritide)
NATRECOR® is the only approved treatment for ADHF that has shown improvement in breathing and a reduction of elevated pressures in the lungs and heart in controlled clinical trials. NATRECOR® has previously been studied in 16 prospective clinical trials involving 2,012 patients treated with the drug, and has been used to treat more than 800,000 acutely decompensated heart failure patients. NATRECOR® is indicated for the intravenous treatment of patients with ADHF who have dyspnea at rest or with minimal activity. In this population, the use of NATRECOR® reduced pulmonary capillary wedge pressure and improved patient reported dyspnea.



IMPORTANT SAFETY INFORMATION

HYPOTENSION
NATRECOR® may cause hypotension and should be administered only in settings where blood pressure can be monitored closely. If hypotension occurs during administration of NATRECOR® the dose should be reduced or discontinued. At the recommended dose of NATRECOR®, the incidence of symptomatic hypotension (4%) was similar to that of IV nitroglycerin (5%). Asymptomatic hypotension occurred in 8% of patients treated with either drug. In some cases, hypotension that occurs with NATRECOR® may be prolonged. The mean duration of symptomatic hypotension was longer with NATRECOR® than IV nitroglycerin (2.2 versus 0.7 hours, respectively). NATRECOR® should not be used in patients with systolic blood pressure less than 90 mm Hg or as primary therapy in patients with cardiogenic shock. The rate of symptomatic hypotension may be increased with a baseline blood pressure less than 100 mm Hg, and NATRECOR® should be used cautiously in these patients. In earlier trials, when NATRECOR® was initiated at doses higher than the 2 mcg/kg bolus followed by a 0.010 mcg/kg/min infusion, the frequency, duration, and intensity of hypotension was increased. The hypotensive episodes were also more often symptomatic and/or more likely to require medical intervention. NATRECOR® is not recommended for patients for whom vasodilating agents are not appropriate and should be avoided in patients with low cardiac filling pressures.

RENAL
NATRECOR® may affect renal function in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with NATRECOR® may be associated with azotemia. In the VMAC trial, through day 30, the incidence of elevations in creatinine to more than 0.5 mg/dL above baseline was 28% and 21% in the NATRECOR® and nitroglycerin groups, respectively. When NATRECOR® was initiated at doses higher than 0.010 mcg/kg/min, there was an increased rate of elevated serum creatinine over baseline compared with standard therapies, although the rate of acute renal failure and need for dialysis was not increased.

MORTALITY
In the prior seven clinical trials, through 30 days, 5.5% in the NATRECOR® treatment group died as compared with 4.3% in the group treated with other standard medications. In five clinical trials, through 180 days, 21.5% in the NATRECOR® treatment group died as compared with 20.7% in the group treated with other medications.