Scios Announces Results From Exploratory Nesiritide Study Providing Important New Renal and Mortality Safety Data with a Neutral Effect on the Primary Endpoint
- Category: Proteins and Peptides
- Published on Monday, 26 March 2007 03:00
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MOUNTAIN VIEW, CA, USA and NEW ORLEANS, LA USA | Mar 25, 2007 | Scios Inc. announced today that an exploratory, 920-patient, Phase 2 study of nesiritide (NATRECOR(R)) showed a neutral effect on the primary endpoint, a composite of death and cardiorenal hospitalization at 12 weeks, and provides important renal and mortality safety data on nesiritide in patients with advanced chronic decompensated heart failure (CDHF) receiving serial outpatient infusions.
Data from the study, known as FUSION II (Follow-Up Serial InfusiOns of NATRECOR(R) in Advanced Heart Failure), were presented during a late-breaking clinical trial session at the American College of Cardiology's 56th Annual Scientific Session in New Orleans (presentation #402-9). Scios also announced that it plans to submit the safety data from this and other recent trials to the U.S. Food and Drug Administration (FDA).
NATRECOR(R) is the only FDA-approved intravenous treatment for patients with acutely decompensated congestive heart failure (ADHF) who have dyspnea (shortness of breath) at rest or with minimal activity.
FUSION II was designed to assess the long-term safety and outcomes at six months of once- or twice-weekly infusions of nesiritide compared to placebo in persistently symptomatic CDHF patients. All patients received ongoing intensive heart failure disease management, including optimization of standard heart failure medications and once or twice weekly outpatient clinic visits. Patients who participated in this trial had to have two prior recent hospitalizations, either NYHA class III or IV heart failure and had to have been out of the hospital for at least five days prior to enrollment in the trial.
The study demonstrated comparable renal and mortality effects in both study arms. In addition, there was no statistically significant difference in the primary endpoint between patients receiving nesiritide compared to patients receiving placebo infusions when each was added to optimal heart failure medications, significant use of indicated heart failure devices and intensive disease management.
"The safety findings from the FUSION II trial and other recent clinical studies should be reassuring for physicians who use nesiritide to treat patients according to its currently labeled indication and who are evaluating the drug in ongoing investigations," said Clyde W. Yancy, M.D., Principal Investigator of FUSION II and Medical Director of the Baylor Heart and Vascular Institute at Baylor University Medical Center at Dallas. "The relatively low clinical event rates observed in both treatment groups are consistent with previous investigations that have demonstrated the utility of rigorous disease management employing optimal medical and device therapies in the improvement of patient outcomes. This is an important message for practitioners."
In multiple rigorously-controlled clinical trials published in peer- reviewed medical journals, NATRECOR(R) was shown to significantly reduce pulmonary capillary wedge pressure and improve patient-reported dyspnea, an important symptom to relieve in patients with exacerbations of heart failure. Since NATRECOR(R) was approved by the FDA in August 2001, more than 800,000 ADHF patients in the United States have been treated with the drug.
FUSION II Study Design and Results
As a follow-up to the FUSION I study, which showed promising initial results in the advanced CDHF patient population, in March 2004 investigators began the prospective, randomized, placebo-controlled, double-blind, multicenter FUSION II trial to further assess the long-term outcomes in this patient group. The study enrolled 920 patients with advanced CDHF at more than 150 sites in the United States and abroad and followed study participants for a minimum of six months.
This Phase 2 trial was designed to further assess the safety, outcomes and optimal dosing frequency of nesiritide in an outpatient setting compared to placebo as a post-hospitalization treatment strategy in patients with advanced CDHF. The primary endpoint was a composite of all-cause mortality and/or cardiorenal hospitalization at 12 weeks. The study also measured numerous safety parameters, including effect on renal function and mortality.
Primary Composite Endpoint
Nesiritide Placebo *P-value
hospitalization+ 36.7 % 36.8 % 0.79
mortality 9.5 % 9.6 % 0.98
hospitalization 32.9 % 33.9 % 0.95
*P-value: Nesiritide vs. placebo stratified by dose group
+Modified intent-to-treat (ITT): all treated ITT patients
The intensive disease management provided in this study is not the current standard of care for patients with advanced CDHF. Patients saw a health care provider once or twice weekly for four to six hours per visit, allowing opportunity for optimization of evidence-based therapies for heart failure.
"This trial provides another important element in the evidence base about chronic decompensated heart failure," said Robert M. Califf, M.D., Vice Chancellor for Clinical Research and Professor of Medicine in the Division of Cardiology at Duke University Medical Center. "Although nesiritide did not show additional benefit compared to placebo when given serially in CDHF outpatients, these data are reassuring with regard to previous concerns about renal toxicity and mortality outcomes. Now that we have this important safety information from FUSION II, we can move forward with excitement into the largest ever global trial in ADHF to assess the impact of nesiritide on health outcomes in the acute phase of the illness."
The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) study, chaired by Dr. Califf at the Duke Clinical Research Institute, is a well-controlled, global, multi-center outcomes study of approximately 7,000 ADHF patients, conducted under the guidance of an independent executive committee and data safety monitoring board.
"We are pleased with the growing body of renal- and mortality-related safety information collected from well-controlled clinical trials of NATRECOR(R), most recently with NAPA results and these new data," said Roger Mills, M.D., Vice President, Medical Affairs at Scios. "We remain confident in the ability of NATRECOR(R) to safely relieve symptoms for acute heart failure patients. We will continue to support the robust clinical development program of this important therapy."
About NATRECOR(R) (nesiritide)
NATRECOR(R) is the only approved treatment for ADHF that has shown improvement in difficulty breathing and reduction of elevated wedge pressures in the lungs in controlled clinical trials. NATRECOR(R) has 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(R) 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(R) reduced pulmonary capillary wedge pressure and improved patient reported dyspnea. For full Prescribing Information, visit http://www.natrecor.com. See Important Safety Information below.
About Scios Inc.
Scios Inc., a wholly-owned subsidiary of Johnson & Johnson, is a biopharmaceutical company headquartered in Mountain View, California. Scios is developing novel treatments for cardiovascular disease. The company's disease- based technology platform integrates expertise in protein biology with computational and medicinal chemistry to identify novel targets and rationally design small molecule compounds and peptides for markets with unmet medical needs. For more information, visit http://www.sciosinc.com.
IMPORTANT SAFETY INFORMATION
NATRECOR(R) (nesiritide) may cause hypotension and should be administered only in settings where blood pressure can be monitored closely. If hypotension occurs during administration of NATRECOR(R) the dose should be reduced or discontinued. At the recommended dose of NATRECOR(R), 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(R) may be prolonged. The mean duration of symptomatic hypotension was longer with NATRECOR(R) than IV nitroglycerin (2.2 versus 0.7 hours, respectively). NATRECOR(R) should not be used in patients with systolic blood pressure <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 <100 mm Hg, and NATRECOR(R) should be used cautiously in these patients. In earlier trials, when NATRECOR(R) 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(R) is not recommended for patients for whom vasodilating agents are not appropriate and should be avoided in patients with low cardiac filling pressures.
NATRECOR(R) 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(R) may be associated with azotemia. In the VMAC trial, through day 30, the incidence of elevations in creatinine to >0.5 mg/dL above baseline was 28% and 21% in the NATRECOR(R) and nitroglycerin groups, respectively. When NATRECOR(R) 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.
In the seven NATRECOR(R) clinical trials, through 30 days, 5.5% in the NATRECOR(R) 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(R) treatment group died as compared with 20.7% in the group treated with other medications. There is not enough information to know about the effect of NATRECOR(R) on mortality. See full Prescribing Information at http://www.natrecor.com.
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson 's Annual Report on Form 10-K for the fiscal year ended January 1, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov or on request from Johnson & Johnson. Johnson & Johnson assumes no obligation to update any forward-looking statements as a result of new information or future events or development.
SOURCE: Scios Inc.