Arena Pharmaceuticals has announced positive 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 PVR 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 PVR compared to the placebo arm (P=0.03) and a 20.1% improvement in PVR compared to baseline. Additionally, adverse events observed in the study were consistent with other prostacyclin treatments for the management of PAH, with headache, nausea, diarrhea, jaw pain and flushing being the most commonly reported adverse events. The company plans to present full study results at future medical congresses.
"The positive outcome of this phase 2 trial in a contemporary PAH patient population is an important milestone in the development of ralinepag for the treatment of patients suffering from this grievous illness," stated Preston Klassen, M.D., MHS, Executive Vice President, Research and Development and Chief Medical Officer of Arena. "It is exciting to see the positive nonclinical pharmacological profile translating into potentially the first oral prostacyclin therapy that may approach consistent therapeutic levels without the complexity of parenteral (IV) therapy. These data give us confidence to move expeditiously toward a phase 3 clinical program."
Vallerie McLaughlin, M.D., Kim A. Eagle MD Endowed Professor of Cardiovascular Medicine at the University of Michigan and Director of the Pulmonary Hypertension Program, added, "PAH is a complex and serious disease, often with a poor prognosis despite the use of currently available treatments. New therapeutic options to manage patients with PAH are needed. The results of this phase 2 study of ralinepag, in patients already receiving, in most cases, multiple background therapies, showed a clinically meaningful improvement in PVR, a well-established indicator of treatment benefit, believed to be correlated with long-term clinical outcomes in patients with PAH."
The phase 2 study was a randomized, double-blind, placebo-controlled, dose-ranging study in 61 adult patients with PAH, 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 (PVR) 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 (APD811) is an oral, next-generation, selective IP receptor agonist targeting the prostacyclin pathway and intended for the treatment of pulmonary arterial hypertension (PAH). Arena discovered and developed this drug candidate internally. 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 PAH. Ralinepag is an investigational compound that is not approved for any use in any country.
Pulmonary Arterial Hypertension (PAH) 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 PAH 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 PAH, but they do not provide a cure, and in many patients the disease will progress despite treatment.