Beraprost sodium MR for the treatment of pulmonary arterial hypertension

Introduction: Parenteral prostacyclins are considered the gold standard treatment of severe pulmonary arterial hypertension (PAH). However, the technical and clinical burden of their continuous parenteral administration has led to the development of long-acting oral analogs.Areas covered: Following suggestive uncontrolled studies, an initial 3-month randomized placebo-controlled trial of the oral prostacyclin analog beraprost sodium (BPS) was completed, demonstrating significant improvement in the primary endpoint, which was the six-minute walk test. However, a subgroup analysis revealed that only idiopathic PAH patients benefited from the drug, secondary end points were negative and dosing was limited by side effects. A second 1-year randomized trial with a primary end point combining clinical stability and exercise capacity was negative. A secondary analysis revealed significant improvement after BPS intake at 6 months. Recent open-label studies with a modified release BPS formulation (BPS-MR) suggested long-term improvement in exercise capacity and clinical state in PAH patients. Randomized controlled trials with BPS-MR are underway but have been slowed by regulatory requirements of single optical isomer reformulation of BPS-MR (BPS-414d-MR).Expert opinion: BPS is efficacious in PAH but has failed until now in randomized controlled trials mainly because of side effects limiting dosing. Successive reformulations will hopefully produce better tolerated, purer and longer-acting preparations.