Long-Term Survival, Safety and Tolerability with Selexipag in Patients with Pulmonary Arterial Hypertension: Results from GRIPHON and its Open-Label Extension

Nazzareno Galiè, Sean Gaine, Richard Channick, J. Gerry Coghlan, Marius M. Hoeper, Irene M. Lang, Vallerie V. McLaughlin, Cheryl Lassen, Lewis J. Rubin, Shu Fang Hsu Schmitz, Olivier Sitbon, Victor F. Tapson, Kelly M. Chin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Introduction: In the event-driven GRIPHON randomised-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag. Methods: Patients randomised to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3 days and 30 days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019. Results: Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7 months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomised to selexipag in GRIPHON. Kaplan–Meier survival estimates (95%CI) at 1, 3, 5 and 7 years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively. Conclusions: These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen. Trial Registration: ClinicalTrials.gov Identifiers: NCT01106014 and NCT01112306.

Original languageEnglish (US)
Pages (from-to)796-810
Number of pages15
JournalAdvances in Therapy
Issue number1
StatePublished - Jan 2022


  • Combination therapy
  • Long-term outcomes
  • Open-label extension
  • PAH
  • Pulmonary arterial hypertension
  • Safety
  • Selexipag
  • Survival
  • Tolerability

ASJC Scopus subject areas

  • Pharmacology (medical)


Dive into the research topics of 'Long-Term Survival, Safety and Tolerability with Selexipag in Patients with Pulmonary Arterial Hypertension: Results from GRIPHON and its Open-Label Extension'. Together they form a unique fingerprint.

Cite this