BREATHE-1

Tracleer reduces rate of clinical worsening and improves exercise capacity and functional class status¹

Design	Dosing and duration
Randomized, double-blind, placebo-controlled trial in adult patients with PAH WHO functional class III or IV (n=213)	Tracleer 62.5 mg BID first 4 weeks   Tracleer 125 mg BID or 250 mg BID following 12 weeks
Primary endpoints	Secondary endpoints
Change in exercise capacity at week 16 (6MWD)	Change in functional class status   Clinical worsening   Borg dyspnea index
PAH etiology (Tracleer treatment group)	Background therapies
IPAH: 102 (71%)  SLE: 9 (6%)  SSc: 33 (23%)   Baseline functional class status  FC III: 130 (90%)  FC IV: 14 (10%)	Anticoagulants   Calcium channel blockers   Diuretics   Supplemental oxygen
Results
Significant increase in walk distance at week 161-3
	Improvements in walk distance were apparent by week 4 and maintained for up to 7 months.2
71% relative risk reduction at week 281,2
	Clinical worsening defined as1:   Death   Hospitalization related to PAH   Discontinuation of therapy due to PAH   Initiation of epoprostenol therapy At week 281,2:   26% absolute risk reduction NNT = 4 (NNT = 1 ÷ absolute risk reduction)
100% of Tracleer patients maintained or improved functional class status by week 161,2
*Placebo corrected

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may preclude future use as their disease progresses.

Important safety information

Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.

Potential for serious liver injury (including, after prolonged treatment, 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 through the use of reliable forms of birth control; monthly pregnancy tests should be obtained.

Contraindicated for use with cyclosporine A and glyburide.

Please see full prescribing information including BOXED WARNING.

Review BREATHE-5 results

1. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.
2. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.
3. Data on file, Actelion Pharmaceuticals.