GRIPHON Study on Selexipag

GRIPHON Study on Selexipag

Selexipag is an orally active IP prostacyclin receptor agonist. It is structurally different from prostacyclin. GRIPHON was a phase 3 double blind randomized, placebo controlled trial which randomized 1156 patients with pulmonary arterial hypertension [1]. Patients included those who were not on treatment for pulmonary arterial hypertension and those on stable dose of endothelin receptor antagonist, phosphodiesterase 5 inhibitor or both. 181 centers from 39 countries participated in the GRIPHON study.

Primary endpoint was a composite of death from any cause or complication related to pulmonary hypertension up to the end of treatment, which was defined as 7 days after last intake of trial medication. Primary endpoint event occurred in 41.6% of the placebo group and 27% of the selexipag group. 81.9% of the events were due to disease progression and hospitalization. Effect of selexipag was similar in those receiving baseline treatment and in those who were not receiving baseline treatment. Mortality was 105 in the placebo group and 100 in the selexipag group. The difference in mortality was not statistically significant.

18.9% of patients had discontinued study medication prematurely. But sensitivity analysis had shown that this did not affect the final conclusions. Subjective elements in the primary endpoints was another limitation of the study. Adjudication by a three person critical event committee was sought to reduce the bias from this aspect. The endpoints were decided based on the recommendations of the Task Force on End Points and Clinical Trial Design at the 4th World Symposium on Pulmonary Hypertension, 2008 [2].

80% of the patients in the GRIPHON study were already receiving therapy for pulmonary arterial hypertension at baseline. 33% of the enrolled patients were receiving two pulmonary arterial hypertension therapies at baseline. A remarkable feature of the study was that it was able to enroll a large number of patients from a large number of centres spread over 39 countries. Vast majority of patients were in World Health Organization functional class II and III. The study has shown that selexipag can be used either as a single agent or in combination endothelin receptor antagonist and/or phosphodiesterase inhibitor.


  1. Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galiè N, Ghofrani HA, Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV; GRIPHON Investigators. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015 Dec 24;373(26):2522-33. 
  2. McLaughlin VV, Badesch DB, Delcroix M, Fleming TR, Gaine SP, Galiè N, Gibbs JSR, Kim NH, Oudiz RJ, Peacock A, Provencher S, Sitbon O, Tapson VF, Seeger W. End points and clinical trial design in pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S97-S107. 

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