Actelion recently announced in a press release that the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has reconsidered and re-adopted its positive opinion for the use of the oral selective IP prostacyclin receptor agonist Uptravi (selexipag) for the treatment of pulmonary arterial hypertension (PAH). Uptravi was originally discovered and developed by Nippon Shinyaku.
The re-adoption of this opinion is the result of several clarifications requested by the European Commission (EC) regarding Uptravi. An EC decision is expected in the coming months.
This opinion is based on the review of Uptravi’s efficacy and safety data from the GRIPHON study, a long-term, placebo-controlled, Phase 3 clinical trial in 1,156 PAH patients with WHO functional class (FC) I to IV symptoms. Patients received Uptravi in combination with an endothelin receptor antagonist (ERA), a phosphodiesterase type 5 (PDE-5) inhibitor, an ERA plus a PDE-5 inhibitor, or just Uptravi as a monotherapy.
Overall, participants were continuously exposed to selexipag for 4.2 years. In total, 58 percent of the trial’s participants had idiopathic PAH or heritable PAH; 29 percent of participants had connective tissue disorders-related PAH; and 10 percent had corrected simple congenital heart disease-related PAH.
The results showed that Uptravi reduced by 40 percent the risk ofcompared to the placebo. The most frequently reported adverse effects were headaches, diarrhea, nausea, vomiting, jaw pain, myalgia and pain in extremities, arthralgia, and flushing – all of which were more frequent during the up-titration phase, with mild to moderate intensities.
The CHMP recommendation moves Uptravi closer to EMA approval for the long-term treatment of PAH in adults either as a combination therapy in patients insufficiently controlled with an ERA and/or a PDE-5 inhibitor; or as monotherapy in patients who are not eligible for these therapies.
“The prostacyclin pathway is one of the fundamental pathways to be targeted in PAH. However, it has been underutilized, mainly because of the significant burden that the route of administration of existing treatments places on patients and their caregivers,” said Marius Hoeper, a GRIPHON Steering Committee member, in a previous press release.
“This positive opinion moves us a step closer to the EMA-approval of Uptravi (selexipag), with the promise of efficacious oral treatment, supported by excellent long-term outcome results, within reach,” Hoeper said.