PAH Drug Associated with Fewer Deaths, Disease Complications in Phase 3 Study
Data from a Phase 3 clinical trial showed that patients with pulmonary arterial hypertension (PAH) might benefit from selexipag treatment, as the drug was seen to lower the risk of death or PAH-related complications. The study, published in the New England Journal of Medicine, is titled “Selexipag for the Treatment of Pulmonary Arterial Hypertension.”
PAH management currently includes combination therapies that target the endothelin, nitric-oxide and prostacyclin pathways. Selexipag, an orally administered selective prostacyclin-receptor agonist, was evaluated in the GRIPHON trial (NCT01106014) – a multicenter, double-blinded, randomized, and event-driven study on the effects of selexipag in PAH patients. The trial started in December 2009 and finished in October 2014, and was conducted in 181 centers in 39 countries.
According to a press release, the GRIPHON trial involved 1,156 patients, ages 18 to 75, with acquired, heritable or idiopathic PAH. Patients receiving prostacyclin analogues were ineligible for participation. Selected participants were assigned at random in a 1:1 proportion to receive placebo (n=582) or selexipag (n=574). In the starting 12-week dose adjustment stage, selexipag was administered at 200 µg two times a day, with a regular increase until unmanageable side effects were developed or to a maximum tolerable dose of 1600 µg twice daily was reached.
The trial’s primary endpoint were PAH-related complications, including disease progression, death, hospitalization, initiation of parenteral prostanoid therapy or long-term oxygen supply, lung transplantation, and balloon atrial septostomy. Markers that included a decrease of 15% or more in the 6-minute walk distance or additional treatment needs were used to determine a worsening condition. The secondary endpoints were the drug’s effect on exercise capacity, as measure by the 6-minute walk distance and Borg dyspnea index.
The primary endpoint was reported in 397 patients, but death or worsening conditions were greater in the placebo group than the selexipag treatment group — 41.6% versus 27.0%, respectively. Hospitalization and disease progression accounted for 81.9% of these primary endpoint events. Specifically, PAH-related deaths were 23.5% in the placebo group and 17.8% in the selexipag group; death from any cause was 18% (placebo) and 17.4% (selexipag).
At week 26, the 6-minute walk distance had lowered by a median of 9 meters from baseline in the placebo group and increased 4 meters from baseline in the selexipag group.
The team also reported that 7.1% of placebo patients and 14.3% of selexipag patients had to discontinue their assigned regimen due to adverse events. The most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain.
The research team concluded that the risk of death or complications related to PAH was significantly lower in patients under selexipag treatment in comparison to those receiving placebo, supporting the clinical efficacy of the drug as a potential PAH therapy.