Healthcare Industry News: TRACLEER
News Release - March 26, 2007
Bosentan -- Tracleer -- Receives Positive EU Opinion for Reduction of New Digital Ulcerations in Systemic Sclerosis PatientsALLSCHWIL, Switzerland, March 26, 2007 (Healthcare Sales & Marketing Network) -- Actelion Ltd (Swiss:ATLN.SW ) announced today that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), has issued a positive opinion on bosentan (TRACLEER(r)) to extend the use of this dual endothelin receptor antagonist beyond Pulmonary Arterial Hypertension.
The CHMP has recommended that the European Commission approve bosentan (TRACLEER(r)) for the reduction of the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease. The European Commission is expected to make a final decision within two months.
TRACLEER(r) is an oral dual endothelin receptor antagonist, which is currently licensed for the treatment of pulmonary arterial hypertension (PAH Functional Class III and IV in the United States, Class III in Europe) to improve exercise ability and decrease the rate of clinical worsening.(1)
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: ``Actelion has been committed to fully exploring the benefits of dual endothelin receptor antagonism. This indication in Digital Ulceration is the first application outside of pulmonary arterial hypertension. In the coming months, we will ask for regulatory review of the recently generated bosentan data in chronic thromboembolic pulmonary hypertension. Other clinical programs are underway, such as the pivotal BUILD-3 program evaluating the safety and efficacy of bosentan in patients with idiopathic pulmonary fibrosis.''
As vasculopathy is a pivotal feature of many of the complications of systemic sclerosis, patients suffering from the condition are at high risk to develop digital ulcerations and pulmonary arterial hypertension. Digital ulcers are an important and painful complication of systemic sclerosis with approximately 50 percent of people with systemic sclerosis developing digital ulcers during their lifetime.(2) Recent scientific publications estimate that the prevalence of PAH in patients with systemic sclerosis is approximately 12-16%.(3,4)
Regulatory proceedings to extend the label for TRACLEER(r) to also include digital ulcerations are ongoing on a worldwide basis, including the United States.
About Systemic Sclerosis and Digital Ulcerations
Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease characterised by excessive collagen deposition in the skin and internal organs, such as the gastrointestinal tract, kidney, heart and lungs. Symptoms result from vascular dysfunction, inflammation and progressive fibrosis, which lead to occlusion of the microvasculature.
As a result of the vascular injury, complications such as pulmonary arterial hypertension (PAH) (200,000 patients worldwide) and digital ulcers (approx. 5,000 severe cases worldwide every year) can occur. Approximately 50 percent of systemic sclerosis patients suffer from DUs at least once in their disease history. DUs are very painful and result in difficult-to-heal open sores, occurring on fingers and toes, leaving depressed scars and adversely impact the ability to perform work and daily activities, particularly those associated with fingertip function. In severe cases, infection can complicate the course, leading to osteomyelitis and gangrene, where surgery and even amputation may be required.
DUs are caused by a reduction in the lumen of small blood vessels (obliterative vasculopathy as observed in the lung in PAH) that diminishes the blood flow to the fingers and toes. Endothelin, a pathogenic mediator, is implicated in vascular damage in SSc. In addition to causing vasoconstriction, endothelin also has direct deleterious effects, which cause fibrosis, vascular hypertrophy, and inflammation. TRACLEER(r), an endothelin receptor antagonist, is effective in treating PAH in scleroderma patients by blocking the detrimental effects of increased endothelin levels.
RAPIDS-1 (Randomized Placebo-controlled Investigation of Digital ulcers in Scleroderma) was a placebo controlled double-blind clinical trial evaluating the prevention of ischemic digital ulcers in 122 patients with systemic sclerosis at 17 centres in Europe and North America. It was the first specifically designed study to look at prevention of ulcer formation. Furthermore the study is among a very few to demonstrate clinical efficacy in systemic sclerosis.(5)
Patients with systemic sclerosis, who had either a history of at least one digital ulcer over the past 12 months or active digital ulcerations at the time of enrollment, were treated with either bosentan (62.5mg bid for four weeks, then 125mg bid for the next 12 weeks) or placebo. The total number of new ulcers during the treatment period was 1.4 for patients on bosentan versus 2.7 for patients on placebo (p=0.0083) representing a 48% reduction in the number of new digital ulcers.(5)
In late 2003, Actelion initiated a second pivotal Phase III clinical trial, RAPIDS-2 (Randomized Placebo-controlled Investigation of Digital ulcers in Scleroderma) regarding TRACLEER(r) in ischemic digital ulcers secondary to systemic sclerosis. In contrast to the earlier RAPIDS-1 trial, this trial evaluated prevention and healing in a population with more severe forms of the disease at the time of enrollment. The treatment duration was longer and a withdrawal period was implemented in order to assess the evolution of digital ulcerations after treatment interruption. The study enrolled a total of 188 patients in 41 centers worldwide.(6)
Patients with systemic sclerosis and at least one digital ulcer were treated with either bosentan (62.5mg bid for four weeks, then 125mg bid for at least 20 weeks and up to 32 weeks) or placebo. The total number of new ulcers over 24 weeks was 1.9 plus or minus 0.2 for patients on bosentan versus 2.7 plus or minus 0.3 for patients on placebo (p=0.035) representing a 30% reduction in the number of new digital ulcers. The reduction in digital ulcers was more pronounced in patients with more than three active DUs at the start of the study.(6)
About Pulmonary Arterial Hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The function of the heart and lungs is severely compromised, manifested by a limited exercise capacity, and, ultimately, a reduced life expectancy. Approximately 100,000 people in Europe and the United States are afflicted with either primary or secondary forms of the disease related to conditions or tissue disorders that affect the lungs, such as scleroderma, lupus, HIV/AIDS or congenital heart disease.
About TRACLEER(r) in Pulmonary Arterial Hypertension (PAH)
TRACLEER(r), the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH) and made available by Actelion subsidiaries in the United States, the European Union, Japan, Australia, Canada, Switzerland and other markets worldwide.
In clinical trials leading to the marketing approval of the drug, approximately 11% of PAH patients receiving TRACLEER(r) experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or of childbearing age who do not use a reliable method of contraception, must not take TRACLEER(r).(1)
(1) TRACLEER(r) SPC
(2) Black C. Pulmonary arterial hypertension: are we doing enough to identify systemic sclerosis patients at high risk of this rare condition? Rheumatology 2005, 44: 141-142 (3) McGoon M. et al. Chest 2004, 126: 14-34
(4) Distler O. and Pignone A. Rheumatology (Oxford) 2006, 45 Suppl 4:iv22-iv25
(5) Korn J. et al. Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist Arthritis & Rheumatism 2004, Issue 12; 50: 3985-3993
(6) Seibold J. et al. Bosentan prevents occurrence but does not speed healing of digital ulcers in patients with systemic sclerosis (SSc). ACR 2005. Poster presentation L2: 552
Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion's first drug TRACLEER(r), an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets TRACLEER(r) through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan, Canada, Australia and Switzerland. At the end of September 2006, TRACLEER(r) was commercially available in 35 countries worldwide. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium -- the single layer of cells separating every blood vessel from the blood stream. Actelion's over 1,200 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (Swiss:ATLN.SW ).
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