Evaluating oral selexipag in pulmonary arterial hypertension: Insights on survival, safety, and dosing patterns from the complete observation period of GRIPHON and its open-label extension

Background Selexipag, an oral prostacyclin receptor agonist, significantly reduced morbidity/mortality risk versus placebo for patients with pulmonary arterial hypertension (PAH) in GRIPHON. Five-year survival estimates in real-world clinical practice for PAH patients are 57%. With its open-label extension (OLE), GRIPHON presents the longest follow-up in a PAH trial to date. Methods Two main analysis sets were evaluated as follows: selexipag-treated patients i.e., those receiving selexipag in GRIPHON (NCT01106014) or OLE (NCT01112306) and selexipag-long term patients, i.e., those randomized to selexipag in GRIPHON, irrespective of entry into its OLE. Safety was analyzed in both. On-treatment survival was analyzed (Kaplan-Meier [KM] estimates; 95% confidence intervals [CI]) in the overall selexipag long-term patients and by subgroups (individualized maintenance dose, PAH-specific combination therapy and time from diagnosis, and 4-strata risk category), to end of treatment + 30 days. Results Overall, 953 selexipag-treated patients were identified; 574 were selexipag long-term patients. For the latter, median follow-up time from selexipag initiation was 54 months and median exposure duration was 35.8 months (total selexipag exposure: 2105.5 patient-years). KM (95% CI) survival estimates at 5 years were 74% (69-78) overall (n = 176) and 79% (67-87) when selexipag was initiated with an endothelin receptor antagonist and phosphodiesterase 5 inhibitor (n = 26). The most frequently reported adverse events (AEs) were related to known prostacyclin-related effects or underlying disease; AEs leading to selexipag discontinuation were reported in 223 (39%) patients. Conclusions These comprehensive, long-term safety and survival data for selexipag provide the longest follow-up period to date for a PAH therapy. Selexipag’s safety profile, up to 10 years in almost 1000 patients, was consistent with previous observations.