Tracleer and PPH News Long-Term Survival Using Tracleer for PH Faces Scrutiny
by John C. Martin
03-04-05 - A new, oral medication approved as a therapy for primary pulmonary hypertension (PPH) was tested recently in a large study, and the physicians who participated concluded the Tracleer drug improved survival for PPH patients as compared to the odds they might have faced with no treatment.1
3-Year Survival Odds Using Bosentan
Vallerie McLaughlin, MD, an associate professor of Internal Medicine at the University of Michigan and a team of investigators assessed the long-term benefit of bosentan, marketed as Tracleer (Actelion Pharmaceuticals) in a group of 169 primary pulmonary hypertension patients who had taken part in two placebo-controlled clinical trials. The patients were followed for more than 3 years, beginning at the start of the first placebo-controlled trial. The investigators compared the survival chances of each PPH patient taking bosentan versus those of each PPH patient if they had not taken any treatment, based on clinical experience and National Institutes of Health (NIH) data. "Survival estimates [with bosentan] were 96% at 12 months and 89% at 24 months, respectively" wrote McLaughlin and her team. "In contrast, predicted survival [without treatment] was 69% and 57%, respectively." After 2 years of follow-up, 70 percent of primary pulmonary hypertension patients were still taking bosentan alone, without the need for additional therapies. Treatment with the oral drug was well tolerated, the researchers reported, although they did note a 10% increased incidence of elevated liver enzymes, thereby requiring monthly liver enzyme monitoring. (Increased liver enzymes are indicators that liver damage may have occurred.) McLaughlin's group found that indicators of the worse prognosis in any one primary pulmonary hypertension patient were end-stage PH (NYHA functional class IV) and a reduced walking distance in a standard 6-minute test. Bosentan was approved by the FDA in 2001 to improve exercise ability and reduce disease progression in people with pulmonary hypertension. It is an oral medication, classified as a endothelin receptor antagonist (ERA). ERAs work by blocking endothelin-1, a hormone that plays a role in narrowing blood vessels. Researchers have found increased levels of endothelin-1 in the lung tissue and plasma of PH patients, suggesting it plays a role in the pathology of the disease.2 'Longer Information Will Be of Interest'
In an editorial related to the study,3 Marc Humbert, MD, in the Service de Pneumologie at Hôpital Antoine-Béclère in Clamart, France notes several limitations of this study admitted by the authors. "Presumably, subjects selected for randomized studies have a better general condition and standard of care than patients treated 20 years ago," Humbert wrote. "Therefore, survival estimated in the 1980s with the NIH [data used in this study] is certainly a pessimistic comparator." "Nevertheless, the NIH equation has been validated and still represents the best available tool for comparative studies," he added. Humbert also noted that the exposure to the drug was relatively short in this study, "and longer information will be of interest to determine whether add-on or switch to another class of drug is required in the long term, and what the exact prognosis of these patients is." Other Trials Needed
Finally, Humbert emphasized that there is a significant need for long-term observational studies of all the medications currently available for PH (Flolan/GlaxoSmithKline, Remodulin/United Therapeutics and bosentan) in terms of their effects on survival and quality of life, their side effects, and their costs. "As head-to-head comparisons of currently approved therapies are not available, the choice of optimal treatment will be dictated by clinical experience and drug availability, as well as patient preference." 1. McLaughlin VV, Sitbon O, Badesch DB et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005 Feb;25(2):244-9.
2. Popa A. Center for Continuing Education. The Cleveland Clinic. Bosentan (Tracleer), a new agent for the treatment of pulmonary arterial hypertension. Available at: https://www.clevelandclinicmeded.com/medical_info
/pharmacy/marapr2002/bosentan.htm. Accessed March 3, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
Myogen Vaults Higher on Trial Data
By TSC Staff
12/12/2005 - Myogen (MYOG:Nasdaq - commentary - research - Cramer's Take) said a late-stage trial of ambrisentan, a proposed treatment for pulmonary arterial hypertension, met its primary goal, its main secondary target and several other marks, sending its shares rocketing higher in premarket trading.
The Colorado-based biopharmaceutical company saw its shares jump $9.74, or 50.5%, to $29.01 on the news.
Myogen said the trial's primary effectiveness endpoint was to improve the patients' capacity for exercise, while the key secondary aim was to increase the length of time until clinical worsening was observed.
Pulmonary arterial hypertension is characterized by severe constriction of the blood vessels in the lungs. The condition leads to very high pulmonary arterial pressure, making it difficult for the heart to pump blood through the lungs. Patients with this type of hypertension suffer from extreme shortness of breath, and those who have it can ultimately die of heart failure.
The disease can occur with no known underlying cause, or it can result from connective tissue disorders, congenital heart defects, cirrhosis of the liver or HIV infection. About 200,000 people worldwide have pulmonary arterial hypertension.
Ambrisentan is what's called a selective endothelin receptor antagonist. Endothelin is a hormone that plays a critical role in controlling blood flow and cell growth. Myogen believes agents that block the detrimental effects of endothelin may provide beneficial treatments for conditions like pulmonary arterial hypertension.
The drug has received the orphan designation in the U.S. and European Union nations. Orphan-drug status is granted to products that treat rare diseases, and it provides companies with seven years of marketing exclusivity.
Myogen said headaches were the most frequent adverse event reported in the trial.
Research Provides Promising Evidence of New Drug Therapies in Lethal Lung Disease
MADRID, Spain, April 7 /PRNewswire/ -- Several promising new treatments may prolong lives as well as improve the quality of life for people living with pulmonary arterial hypertension. Research showing benefits of these novel drug therapies for lethal lung disease will be discussed today at the 26th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT).
Pulmonary arterial hypertension (PAH), high blood pressure in the pulmonary arteries in the lungs, is a life-threatening disease. Therapeutic options have, until recently, been limited and many patients with PAH faced lung transplantation. In recent years, research has identified a number of novel drug therapies that have shown to improve both quality and quantity of life in patients with this very serious illness.
During the ISHLT Meeting, researchers will discuss the results of new trial evidence of drugs including the endothelin antagonists Sitaxentan and Bosentan, prostenoids including Trepostenil and Prostacyclin, and Viagra(R) (sildenafil citrate), marketed as Revatio(TM) for PAH, used as single agents and in combination.
PAH is caused when the smaller blood vessels in the lungs become more resistant to blood flow forcing the right ventricle of the heart to work harder to pump enough blood through the lungs. For example, Revatio (Viagra) helps patients by causing the pulmonary arteries to dilate which lessens the lungs resistance to blood flow and reduces the workload of the heart.
"It is an extremely exciting time for physicians involved in the care of patients with pulmonary arterial hypertension because of the explosion of novel drugs within the last few years," commented Paul A. Corris, Professor of Thoracic Medicine at the University of Newcastle upon Tyne, UK and Director, North of England Pulmonary Vascular Service. "Although these drugs cannot yet be considered a cure for pulmonary arterial hypertension, results of medical therapy are extremely encouraging for patients who have this serious disease and there is good evidence to show that patients who otherwise would have required urgent listing for lung transplantation may be treated satisfactorily in the interim with these drugs."
Contact: Melissa Aguillon
Phone: +1-210-745-2611
E-mail: maguillon@masonpr.com
|
