Report on first patients to receive investigational treatment for CHF on sustained basis
SEATTLE -- Continued treatment with the TNF inhibitor ENBREL® (etanercept) was generally well-tolerated by the first twelve patients with advanced heart failure treated with the drug for nine months. In addition, there was evidence of sustained improvement in the New York Health Assessment (NYHA) class in these patients, according to results of a follow-up study presented today at the American College of Cardiology 49th Annual Scientific Sessions in Anaheim. ENBREL currently is under clinical development for chronic heart failure by Immunex (NASDAQ: IMNX) and Wyeth Ayerst, a division of American Home Products Corporation (NYSE: AHP).
In the another arm of the study, 31 patients (placebo = 10; etanercept = 21) discontinued their study drug and were followed for three months to evaluate what happened when treatment was stopped. Consistent with expected loss of drug effect, patients lost the improvement they had experienced while on treatment. Importantly, however, they experienced no rebound of their disease and did not get acutely worse from baseline.
Today's presentation by Biykem Bozkurt, MD, of Baylor College of Medicine, was based on results of a six-month follow-up study designed to look at the continued tolerability of ENBREL after an initial three-month placebo-controlled trial with the drug.
"We are further encouraged by these follow-up results of ENBREL in chronic heart failure patients," said Peggy Phillips, chief operating officer at Immunex. "This is our first data from patients with chronic heart failure who have nine months of experience being treated with ENBREL."
In the original study, 47 patients with advanced heart failure were studied for 3 months in a randomized, double-blind, placebo-controlled trial comparing twice-weekly injections of ENBREL at either 5mg/m2 or 12mg/m2, to placebo. In that study, measurements of clinical activity at three months suggested improvement for patients receiving ENBREL in NYHA classification, left ventricular ejection fraction, quality of life (physical dimension), and in a clinical composite score. In addition, there appeared to be a dose response in each of the categories above.
Forty-three patients continued in the follow-up study in two open-label arms. Twelve patients were assigned to continue to receive ENBREL in twice-weekly subcutaneous injections of 12 mg/m2 for six months.
Results indicated that continued treatment with ENBREL for nine months was generally well-tolerated, with no increase in frequency of adverse events. In the original study, the incidence of adverse events was similar in all treatment groups. Chest pain was reported in 19 percent of patients receiving placebo, 19 percent of patients receiving ENBREL 5mg/m2, and 7 percent of patients receiving ENBREL 12 mg/m2. Diarrhea was reported by 13 percent, 7 percent and 19 percent of patients receiving placebo, ENBREL 5mg/m2 and ENBREL 12mg/m2, respectively.
The potential of ENBREL in the treatment of moderate to severe heart failure (NYHA class II-V) will be further evaluated in two large-scale, ongoing, Phase II/III trials. Immunex is enrolling 900 patients for the RENAISSANCE trial (Randomized Etanercept North American Strategy to Study Antagonism of Cytokines). A companion trial named RECOVER (Research into ENBREL: Cytokine Antagonism in Ventricular Dysfunction) is being conducted in Europe, Australia and New Zealand by Wyeth-Ayerst Global Pharmaceuticals. The two studies will be combined to analyze morbidity and mortality. The combined studies will be known as the RENEWAL (Randomized Etanercept Worldwide Evaluation) trial. If you are interested in enrolling in the RENAISSANCE trial, call 1-800-IMMUNEX.
Nearly five million Americans have chronic heart failure today. Of these, about 1.5 million have NYHA class III-IV chronic heart failure. Chronic heart failure is one form of heart disease that results when the heart is damaged from diseases such as high blood pressure, a heart attack, poor blood supply to the heart, a defective heart valve, atherosclerosis, rheumatic fever or heart muscle disease. The failing heart keeps working, but becomes inefficient, resulting in fluid retention and shortness of breath, fatigue and exercise intolerance. The condition often progresses and becomes irreversible.
The Role of TNF in Chronic Heart Failure
Research has shown that (TNF), an immune system protein, is present in increased amounts in damaged heart tissue. TNF exerts its effects by interacting with specific TNF receptors that are on the surface of cells. When TNF binds with TNF receptors, it sets off a chain of events within the cell that may lead to further damage to the heart.
ENBREL is a genetically engineered soluble cytokine receptor, based on the naturally occurring soluble TNF receptor, that works by binding to TNF and preventing it from interacting with cell surface receptors that are on the cells in the heart and circulatory system.
About ENBREL
ENBREL has been approved by the U.S. Food and Drug Administration for the reduction in signs and symptoms of moderately to severely active rheumatoid arthritis (RA) in juvenile (JRA) and adult patients who have an inadequate response to one or more disease modifying anti-rheumatic drugs.
IN POSTMARKETING USE, SERIOUS INFECTIONS AND SEPSIS, INCLUDING FATALITIES, HAVE BEEN REPORTED. MANY OF THESE EVENTS OCCURRED IN PATIENTS PREDISPOSED TO INFECTIONS, SUCH AS THOSE WITH ADVANCED OR POORLY CONTROLLED DIABETES. DISCONTINUE ENBREL IN PATIENTS WITH SERIOUS INFECTIONS OR SEPSIS. DO NOT START ENBREL IN THE PRESENCE OF SEPSIS, INFECTION (INCLUDING CHRONIC OR LOCALIZED), OR ALLERGY TO ENBREL OR ITS COMPONENTS. USE CAUTION IN PATIENTS PREDISPOSED TO INFECTION. The most frequent adverse events in adult clinical trials (n=349) were injection site reactions (ISR) (37%), infections (35%), and headache (17%). Malignancies were rare (<1%). Only the rate of ISR was higher than placebo. In a JRA study (n=69), infections (62%), headache (19%), abdominal pain (19%), vomiting (13%) and nausea (9%) occurred more frequently than in adults. The types of infections reported in JRA patients were generally mild and consistent with those commonly seen in outpatient pediatric populations. Serious adverse events were reported rarely were varicella (3%), gastroenteritis (3%), depression/personality disorder (1%), cutaneous ulcer (1%), and esophagitis/gastritis (1%).
Immunex manufactures ENBREL. Immunex and Wyeth-Ayerst market ENBREL in North America. Other Wyeth-Ayerst affiliates will market ENBREL outside of North America. Additional information about ENBREL, including full prescribing information, can be found on the company-sponsored web site at (www.ENBREL.com) or by calling toll-free 1-888-4ENBREL (1-888-436-2735).
Immunex is a biopharmaceutical company dedicated to developing immune system science to protect human health. The company's products offer hope to patients with cancer, inflammatory and infectious diseases.
American Home Products Corporation's Wyeth-Ayerst division is a major research-oriented pharmaceutical company with leading products in the areas of women's health care, cardiovascular disease therapies, central nervous system drugs, anti-inflammatory agents, vaccines and generic pharmaceuticals.
American Home Products owns a majority interest in Immunex. AHP is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of prescription drugs and over-the-counter medications. It is also a leader in vaccines, biotechnology, agricultural products and animal health care.
NOTE: This release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development, regulatory approvals, patent litigation, product commercialization and other risks described from time to time in the SEC filings by Immunex and American Home Products respectively, including the most recently filed 10-K and 10-Q forms. For more information, please refer to www.immunex.com.