Actelion, Ltd., a biopharmaceutical company headquartered in Switzerland and focused on the discovery, development, and commercialization of innovative treatments for unmet medical needs, recently announced that additional important results from its pivotal Phase III GRIPHON clinical trial on pulmonary arterial hypertension (PAH) patients with its lead investigational drug selexipag (Uptravi®) will be presented in a poster at the American College of Chest Physicians’ CHEST Annual Meeting taking place in Montréal, Canada.
Dr. Richard Channick from Massachusetts General Hospital in Boston will present the poster entitled, “Individualized dosing of selexipag based on tolerability in the GRIPHON study shows consistent efficacy and safety in patients with pulmonary arterial hypertension” on October 28 at 1:30 p.m. The abstract can be found online.
In this pivotal, double-blind, placebo-controlled, event-driven trial, 1,156 patients suffering from PAH were randomized 1:1 to placebo or selexipag. Patients were treated for up to 4.3 years, with median exposure to study treatment of 63.1 weeks for patients on placebo (n=582), and 70.6 weeks for patients on selexipag (n=574).
At enrollment, 80% of patients were already receiving therapy for PAH, with 15% receiving endothelin receptor antagonist (ERA) mono therapy, 32% receiving phosphodiesterase-5 inhibitor (PDE-5i) monotherapy, and 33% receiving a combination of both an ERA and a PDE-5i. At baseline, 47% of patients were in WHO Functional Class I/II and 53% in Functional Class III/IV.
In March 2015, the company reported that selexipag significantly reduced the risk of a morbidity/mortality event by 40% versus placebo (p<0.0001). Furthermore, selexipag was found to improve the long-term outcomes in an investigational trial of patients already treated with ERA and PDE-5i combination therapy, with ERA or PDE-5i monotherapy, and in treatment-naïve patients.
Selexipag (Uptravi®), originally discovered and synthesized by Nippon Shinyaku, is a potent, orally available, selective prostacyclin IP receptor agonist. The therapy selectively targets the prostacyclin receptor (also called IP-receptor). The IP receptor is one of five types of prostanoid receptor. Prostacyclin activates the IP receptor inducing vasodilation and inhibiting proliferation of vascular smooth muscle cells. Selexipag, unlike prostacyclin analogs, is selective for the IP receptor over other prostanoid receptors.
Although Pulmonary arterial hypertension (PAH) is a rare disease, with an estimated prevalence of 15-50 cases per million, the prevalence of PAH in certain at-risk groups is substantially higher. In HIV-infected patients, for example, the prevalence is 0.5%; in patients with systemic sclerosis, it has been reported to be 7–12%; and in patients with sickle cell disease, the prevalence is around 2–3.75%.