Actelion, Ltd., recently announced the approval of Uptravi (selexipag) by the Therapeutic Goods Administration (TGA) of Australia and the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) for the treatment of pulmonary arterial hypertension (PAH).
Uptravi, an orally active selective IP prostacyclin receptor agonist, was approved to treat idiopathic PAH, heritable PAH, PAH associated with connective tissue disease, PAH associated with congenital heart disease with repaired shunts, and PAH associated with drugs and toxins, in patients with WHO functional class II, III, or IV symptoms.
The approval was partially based on the results of the Phase 3 GRIPHON trial, which were published in the New England Journal of Medicine in December 2015.
GRIPHON was a multicenter, double-blind, placebo-controlled trial evaluating the long-term efficacy and safety of oral selexipag in 1,156 patients with symptomatic PAH, and the largest study ever in PAH. The exposure to selexipag was up to 4.2 years and the mean duration of the treatment was 76.4 weeks for patients that received selexipag, versus 71.2 weeks for those on placebo. The findings established the effectiveness and safety of Uptravi in PAH patients with WHO functional class II-III symptoms.
The most frequently reported mild to moderate adverse events of Uptravi are jaw pain, arthralgia, extremity pain, headache, myalgia, diarrhea, nausea and vomiting, and flushing.
“The approval of Uptravi represents a major step forward in disease management for the PAH communities in both Australia and New Zealand. Until now the options for treatments targeting the prostacyclin pathway have been limited, and were burdensome for the patient. Uptravi offers patients an oral treatment that targets the prostacyclin pathway, opening the way for oral combination therapies with proven long-term outcome benefits,” Simon Eade, head of Actelion Asia Pacific Region, said in a press release. “We will now work to secure reimbursement and make Uptravi available to patients.”
Uptravi was approved for PAH treatment by the U.S. Food and Drug Administration in December 2015, and received a positive opinion from the Committee for Medicinal Products for Human Use, recommending marketing authorization in the European Union, in January 2016. That opinion is now under review by the European Commission.
PAH is a chronic disease characterized by an increase of blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature. It leads to shortness of breath, dizziness, fainting, leg swelling, and other symptoms.
Although 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. For example, the prevalence in HIV-infected patients is 0.5 percent, in patients with systemic sclerosis between 7 percent and 12 percent, and in patients with sickle cell disease around 2 percent and 3.75 percent.