By Eleanor McDermid, Senior medwireNews Reporter
Selexipag, alone or in combination with other classes of pulmonary arterial hypertension (PAH) medication, reduced the composite rate of disease complications and deaths among patients in a phase III trial.
The significant 40% reduction in this primary endpoint was driven by a decreased rate of PAH complications among patients taking the oral selective IP prostacyclin-receptor agonist in the Prostacyclin (PGI2) Receptor Agonist In Pulmonary Arterial Hypertension (GRIPHON) study.
In all, 27.0% of the 574 patients randomly assigned to receive selexipag had a primary endpoint event, compared with 41.6% of the 582 assigned to the placebo group. But only 4.9% and 3.1% of patients in the respective groups died, with no significant difference between the two.
However, Olivier Sitbon (Hôpital de Bicêtre, Paris, France) and co-researchers note that clinical deterioration usually precedes death in PAH patients, and the study design allowed deteriorating patients to switch to open-label selexipag or another PAH treatment.
“The evaluation of death is subject to this limitation”, they write in The New England Journal of Medicine.
Almost 80% of the patients were already taking other PAH-specific medications at baseline, with a third taking more than one.
Disease progression and hospitalisation for worsening PAH accounted for 81.9% of all primary endpoint events, with other events being a need for parenteral prostanoid therapy, long-term oxygen therapy, lung transplantation or balloon atrial septostomy.
Patients receiving selexipag started at a dose of 200 μg twice daily, which was increased during a 12-week dose-adjustment period to the highest tolerated dose or a maximum of 1600 μg twice daily. Treatment continued until a prespecified number of primary endpoints had occurred; patients in the selexipag group received the drug for a median of 70.7 weeks and those taking placebo did so for a median of 63.7 weeks.
Among secondary endpoints, patients’ 6-minute walk distance increased by a median of 4.0 metres in the selexipag group but decreased by 9.0 metres in the placebo group – a significant 12.0 metre difference.
Adverse events were as expected for a prostacyclin therapy, with rates of headache, diarrhoea and nausea most likely to be elevated in the selexipag versus the placebo group.
“Overall, these adverse events were typically mild to moderate in severity and resulted in discontinuation in only a minority of cases”, say the researchers.
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