The first approved endothelin receptor antagonist (ETRA) for the treatment of pulmonary arterial hypertension (PAH) is bosentan (BOS), an oral, twice-daily, non-selective ETA/ETB ETRA. While a significant advance for PAH, BOS therapy has been complicated by abnormal liver function tests [>3X upper limit of normal (abLFT)] in a controlled trial setting (12% at the labeled dose) and in clinical practice, a finding that has been subsequently seen at varying rates with all ETRAs studied in PAH. Sitaxsentan (SITAX), is an oral, once-daily, highly selective (>6500:1) ETA ETRA in development for PAH which demonstrated lower abLFT rates with 100mg QD in STRIDE-1. These lower abLFT rates were confirmed in STRIDE-2: 6.5% of patients randomized to placebo, 3.2% for SITAX 100mg, 4.9% for SITAX 50mg, and 11.5% for BOS. Here, we report on the long-term LFT rates observed for patients (pts) treated for up to one year with BOS, in accordance with the product label, or SITAX.
STRIDE-2 was an 18 week, multi-center, placebo-controlled study that randomized 246 patients (pts) 1:1:1:1 to PBO, SITAX 100 mg, SITAX 50 mg or open label, efficacy-rater blinded, BOS followed by an extension with pts receiving either BOS or SITAX 100 mg. During the extension, pts on PBO in STRIDE-2 were randomized to SITAX 100mg or BOS; pts on SITAX 50mg received SITAX 100mg and pts on SITAX 100mg or BOS were continued on those treatments.
Kaplan-Meier estimates of time to abLFT at 1 year of exposure are 4.0% for SITAX 100mg and 18.7% for BOS (p = 0.0086).
Long-term treatment with SITAX 100mg QD results in significantly fewer liver function abnormalities than bosentan.
Sitaxsentan 100mg QD has been shown to be safe and effective in the treatment of PAH, with a lower rate of liver function abnormalities than bosentan.
Terrance Coyne, Shareholder Encysive Pharmaceuticals; Employee Encysive Pharmaceuticals; Product/procedure echnique that is considered research and is NOT yet approved for any purpose. Sitaxsentan.