Actelion Pharmaceuticals Ltd

Actelion Pharmaceuticals Ltd

September 22, 2009 07:00 ET

Tracleer Receives Label Extension in Canada for the Treatment of Patients With Mildly Symptomatic WHO Functional Class II Pulmonary Arterial Hypertension

LAVAL, QUEBEC--(Marketwire - Sept. 22, 2009) - Actelion Pharmaceuticals Canada Inc. announced today that Tracleer® (bosentan), a dual endothelin receptor antagonist, has been approved in Canada for the treatment of patients with mildly symptomatic WHO Functional Class II (FC II) pulmonary arterial hypertension (PAH).

Tracleer® has been available to Canadians since 2001, and was previously approved for the treatment of pulmonary arterial hypertension in patients with WHO Functional Class III and IV primary pulmonary hypertension, or pulmonary hypertension secondary to scleroderma or congenital heart disease or human immunodeficiency virus in patients who did not respond adequately to conventional therapy.

Tracleer® is the first PAH treatment ever to be investigated in a clinical study that exclusively enrolled patients with mildly symptomatic WHO FC II. This 185-patient randomized, double-blind, placebo-controlled study provided the basis for this Canadian approval. The indication is now extended to include a prolongation of time to clinical worsening in patients with WHO Functional Class II. (1)

Jacques Archambault, President, Actelion Canada, commented: "The EARLY study has demonstrated that even patients with mild symptoms are at risk of rapid deterioration. I am very proud that Actelion - together with the scientific community - has been able to demonstrate the important role of Tracleer® in delaying disease progression in these patients."

Jacques Archambault continued: "Our dual endothelin receptor antagonist Tracleer® is the only PAH medicine to have demonstrated a delay in disease progression in three independent placebo-controlled, randomized clinical studies. Actelion will now communicate these important clinical findings to the Canadian PAH community to encourage early diagnosis and intervention."

The results from EARLY (Endothelin Antagonist tRial in miLdlY symptomatic PAH patients) - published in "The Lancet" in June, 2008 (2) - document the relentlessly progressive nature of PAH, even in its early stages, and highlight the need for earlier treatment and intervention in PAH management. The PAH progression was evident from the deterioration in all evaluated parameters in the placebo group, including the rate of clinical worsening events. The primary endpoints for the EARLY trial were changes in pulmonary vascular resistance (PVR) and exercise capacity as measured by a 6-minute walk distance (6MWD). PAH progression was assessed by evaluating two secondary endpoints which were time to clinical worsening and change in WHO Functional Class.

The key results of the EARLY study were:

- Significant improvement in PVR, with a reduction of 22.6 percent (p less than 0.0001) after six months of Tracleer compared with placebo.

- 6MWD increased by a mean of 19 meters (p equals 0.0758). Although a positive trend was observed, statistical significance was not seen in the change in 6MWD.

- A significant 77 percent risk reduction in time to clinical worsening (p equals 0.011) was seen after six months of bosentan treatment compared with placebo. Time to clinical worsening was defined by symptomatic progression of PAH, hospitalization for PAH or death. Patients receiving bosentan had a lower incidence of worsening WHO functional class (3.4 percent compared to 13.2 percent when receiving placebo,# equals 0.0285), providing further evidence of delayed PAH progression.

- A subgroup of patients who received concomitant sildenafil also showed improvements in PVR and 6MWD, consistent with the overall results.

- The safety and tolerability profile of bosentan in the EARLY study was consistent with that observed in previous placebo-controlled clinical trials.(3,4)

Dr Sanjay Mehta, London Health Sciences Centre, Ontario, Canada, commented "The results from EARLY show the relentlessly progressive nature of PAH if left untreated, even in its early stages. It is of the utmost importance to screen high risk patients to establish a timely diagnosis of PAH, and then to treat these patients with an evidence-based approach. It is also crucial that all PAH patients, regardless of WHO functional class, are routinely monitored for the earliest signs and symptoms of PAH progression."

There are four WHO Functional Classes (FC) for PAH with Class I being the least severe and Class IV being the most advanced. These reflect the impact of PAH on a patient's life in terms of symptoms and physical limitation. WHO FC II patients are defined as patients with PAH resulting in a slight limitation of physical activity, they are comfortable at rest but ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. (5) Despite being mildly symptomatic, these patients still suffer from a severe and rapidly progressive disease.

Notes to the editor:

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.

PAH is associated with structural changes in both the pulmonary vasculature and the right ventricle. Recent advances (6) in the understanding of the pathogenic factors leading to the pulmonary vascular disease have led to the development of new therapies targeting specific pathways (the prostacyclin pathway; the endothelin pathway; and the nitric oxide pathway) (7). The available therapies have shown positive treatment effects in patients with PAH, but they do not provide a cure, and in many patients the disease will progress. PAH remains a serious life-threatening condition (7,8). Early recognition and an understanding of the selection and timing of therapeutic options remain critical elements in the optimal management of patients with this disorder.

About Tracleer® in Pulmonary Arterial Hypertension (PAH)

Tracleer® (bosentan), the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH); in the United States in PAH Functional Class III and IV to improve exercise capacity and decrease the rate of clinical worsening and in Europe in PAH Functional Class III to improve exercise capacity and symptoms as well as PAH Functional Class II where some improvements have also been shown. In the EU, Tracleer® is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.

Tracleer® has been made commercially available by Actelion subsidiaries in the United States, the European Union, Japan, Australia, Canada, Switzerland and other markets worldwide since 2001. In these seven years of clinical experience, more than 68,500 patients have been treated with Tracleer® (9).

Requires attention to two significant safety concerns: Potential for serious liver injury (including rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring) - Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter. High potential for major birth defects -Pregnancy must be excluded and prevented by two forms of birth control; monthly pregnancy tests should be obtained.


1. Tracleer® Product Monograph
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receptor antagonist bosentan in patients with pulmonary hypertension: a
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9. PSUR - 11th edition

Actelion Ltd

Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion's first drug Tracleer®, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer® 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. 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 2000 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI®).

Contact Information

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    Roland Haefeli
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