Phase 2 results for Ralinepag, an investigational, long-acting, orally administered prostacyclin receptor agonist under development for the treatment of pulmonary arterial hypertension ( PAH ). In this 61-patient study, the primary efficacy analysis demonstrated a statistically significant absolute change from baseline in pulmonary vascular resistance ( PVR ) compared to placebo.
Ralinepag also demonstrated numerical improvement in 6-minute walk distance ( 6MWD ).
Ralinepag improved median pulmonary vascular resistance by 163.9 dyn.s.cm-5 from baseline compared to a 0.7 dyn.s.cm-5 worsening from baseline in the placebo arm ( P=0.02 ).
Patients treated with Ralinepag had a 29.8% improvement in pulmonary vascular resistance compared to the placebo arm ( P=0.03 ) and a 20.1% improvement in pulmonary vascular resistance compared to baseline.
Adverse events observed in the study were consistent with other prostacyclin treatments for the management of pulmonary arterial hypertension, with headache, nausea, diarrhea, jaw pain and flushing being the most commonly reported adverse events.
The phase 2 study was a randomized, double-blind, placebo-controlled, dose-ranging study in 61 adult patients with pulmonary arterial hypertension, WHO/NYHA functional class II-IV.
Study medication was titrated over 9 weeks, followed by a 13-week treatment period.
The primary efficacy analysis was absolute change from baseline in pulmonary vascular resistance at week 22.
Additional endpoints included change from baseline in 6-minute walk test, proportion of subjects who exhibit clinical worsening and safety and tolerability.
Patients who completed week 22 could transition to an open-label ralinepag extension study.
Ralinepag is an oral, next-generation, selective IP receptor agonist targeting the prostacyclin pathway and intended for the treatment of pulmonary arterial hypertension.
Ralinepag's potency on vasodilation, inhibition of proliferation of vascular smooth muscle cells, and inhibition of platelet aggregation, combined with an extended half-life support its application as a potentially best-in-class agent for the treatment of pulmonary arterial hypertension.
Pulmonary arterial hypertension is a rare, chronic, progressive, life-threatening disorder characterized by increased pressure in the arteries that carry blood from the heart to the lungs.
The increased pressure strains the heart, which can limit physical activity, result in heart failure and reduce life expectancy.
Current treatment of pulmonary arterial hypertension falls within four distinct therapeutic classes: endothelin receptor antagonists ( ERAs ), phosphodiesterase-5 ( PDE-5 ) inhibitors, prostacyclin analogues and soluble guanylate cyclase ( SGc ) stimulators.
The available therapies have positive effects in pulmonary arterial hypertension, but they do not provide a cure, and in many patients the disease will progress despite treatment. ( Xagena )
Source: Arena Pharmaceuticals, 2017