HAMBURG, Germany, June 11 /PRNewswire/ -- NovaCardia, Inc. today presented preliminary results from a pilot Phase 3 trial of KW-3902, an adenosine A1 receptor antagonist in development for the treatment of patients with acute congestive heart failure (CHF), that indicate a strong trend toward efficacy for the 30 milligram dose. Patients treated with KW-3902 experienced a higher rate of improvement in dyspnea, or shortness of breath, which is a common symptom of CHF, compared to the placebo group, and the results also show that KW-3902 enhances diuresis and mitigates deterioration of renal function that is often experienced by patients undergoing standard treatment. The findings were summarized by Marco Metra, M.D., University of Brescia, Italy and Gadi Cotter, M.D., Duke University School of Medicine, in a Late-Breaking Trials Session at the European Society of Cardiology's Heart Failure Congress 2007 in Hamburg, Germany.
Drs. Metra and Cotter presented preliminary 14-day data from 276 patients out of 304 total patients enrolled in the pilot Phase 3 trial. Hospitalized patients with acute CHF with renal impairment, which was defined as having creatinine clearance of 20 to 80 milliliters per minute, were randomized to placebo or 10, 20 or 30 milligram doses of intravenous KW-3902 administered daily for up to three days. All patients also received intravenous furosemide. In the double-blind trial, 225 patients received KW-3902 and 79 patients received placebo. The trial was not designed to assess the statistical significance of effects.
The primary endpoint for the pilot Phase 3 trial was the proportion of patients in the categories of treatment failure, success or no change. Treatment success was defined as:
-- improvement in patient-reported dyspnea within 48 hours;
-- physician determination of patient improvement resulting in conversion
from intravenous to oral diuretics; and
-- the absence of treatment failure.
Treatment failure was defined as:
-- readmission to the hospital for heart failure within seven days of the
first dose of KW-3902 or placebo;
-- worsening of heart failure; or
-- worsening renal function.
Patients treated with 30 milligrams of KW-3902 showed higher rates of treatment success and lower rates of treatment failure compared to the placebo group.
The pilot study also showed that 24-hours after treatment, self-reported marked or moderate improvement in dyspnea was observed in 66 percent of the patients who received the 30 milligram dose of KW-3902 as compared to 51 percent in the placebo group.
There were no statistical differences or trends in adverse events observed in the pilot study. The results of the study confirmed that 30 milligrams of KW-3902 is an appropriate dose for NovaCardia's two 600-patient pivotal Phase 3 trials, PROTECT 1 and PROTECT 2, which are currently enrolling participants in the United States, Canada, Europe, Israel and Russia.
KW-3902 is believed to block adenosine-mediated constriction of blood flow to the kidneys and inhibit reabsorption of salt and water by the kidney, thereby increasing urine volume and maintaining renal function in patients with CHF. As renal function deteriorates in patients with CHF, higher doses of diuretics are required in order to reduce fluid overload.
Multiple studies have demonstrated that renal dysfunction is a strong independent predictor of worse short- and long-term outcomes in patients with CHF. In the NovaCardia pilot study, the 30 milligram dose of KW-3902 also showed a positive effect on patients' renal function over time compared to placebo. Although KW-3902 was administered for only the first three days of the trial, an apparent dose response was seen in serum creatinine, a commonly used marker of worsening renal function, at day 14. The study showed no mean change in serum creatinine in patients treated with the highest dose of KW-3902 compared to a 0.2 milligram per deciliter mean increase, or worsening, in participants receiving placebo. These data are consistent with prior findings and indicate that KW-3902 appears to have a persistent effect on renal function. To date, no other vasodilator has demonstrated the selective renal vasodilation attribute of KW-3902 that is critical for preserving renal function.
About Congestive Heart Failure
Congestive heart failure (CHF) is a widespread and debilitating disease most often caused by a weakening or stiffening of the heart muscle, which leads to a progressive loss in the heart's ability to pump blood effectively throughout the body. There are nearly five million people in the United States with CHF, according to the American Heart Association (AHA). With the aging population and more patients surviving the early stages of cardiovascular diseases, the prevalence of CHF is increasing. Approximately 550,000 new cases of CHF are reported in the United States each year, according to the AHA.
NovaCardia is a clinical-stage pharmaceutical company focused on developing drugs to treat major cardiovascular diseases that are underserved by existing therapies. The company has two compounds in clinical development, KW-3902 for congestive heart failure and K-201 (JTV-519) for atrial fibrillation.
NovaCardia cautions you that statements included in this press release that are not a description of historical facts, including implied statements relating to future outcomes of clinical trials, may be forward-looking statements that are subject to risks and uncertainties. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in NovaCardia's business including, without limitation, risks related to difficulties or delays in, testing, obtaining regulatory approval, producing and marketing its products; unexpected adverse side effects or inadequate therapeutic efficacy of its products that could delay or prevent product development or commercialization, or that could result in recalls or product liability claims; the risk that prior clinical trial results may include statistical anomalies and may not be predictive of the outcome of later-stage trials; the scope and validity of patent protection for its products; competition from other pharmaceutical or biotechnology companies; and its ability to obtain additional financing to support its operations. All forward-looking statements are qualified in their entirety by this cautionary statement and NovaCardia undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof.