SUMMARY  

• The phase 3 GRIPHON trial evaluated the long-term efficacy and safety of UPTRAVI tablets in 1156 patients with pulmonary arterial hypertension (PAH).¹ 
• The GRIPHON safety analysis set included a total of 1152 patients.¹ 
  • Thrombocytopenia was identified as an adverse event (AE) of special interest.² 
  • Thrombocytopenia-related AEs were reported in 10 out of 575 patients in the UPTRAVI group and 11 patients out of 577 in the placebo group.³ 
  • Serious adverse events (SAEs) denoting thrombocytopenia were reported in 2 patients (<1%) on UPTRAVI compared with no patients on placebo during GRIPHON.⁴ 
  • There were no discontinuations or deaths due to thrombocytopenia-related AEs during GRIPHON.⁴ 
  • The proportion of patients who had a marked decrease in platelet count (defined as <75 GI/L) was similar between the UPTRAVI (2.2%) and the placebo (2.5%) groups.⁴ 
• The GRIPHON open-label (OL) extension study was an open-label, multicenter study that aimed to assess the long-term safety and tolerability of UPTRAVI in patients with PAH.⁵ 
  • Of the 709 patients on UPTRAVI, SAEs of thrombocytopenia and immune thrombocytopenic purpura were reported in 2 (0.28%) patients and 1 (0.14%) patient, respectively.⁶ 

CLINICAL DATA

GRIPHON Study

The Phase 3 study GRIPHON (Prostacyclin [PGI₂] Receptor agonist In Pulmonary arterial HypertensiON; AC-065A302) was a randomized, multicenter, double-blind, parallel group, placebocontrolled event-driven trial evaluating the efficacy and safety of UPTRAVI tablets in patients with symptomatic PAH. UPTRAVI or matching placebo was initiated at 200 mcg twice daily (BID) and up-titrated weekly in increments of 200 mcg BID until the individual highest tolerated dose was attained (ranging from 200-1600 mcg BID).¹ 

Safety Results

The GRIPHON safety analysis set included a total of 1152 patients across 181 centers and 39 countries who received either UPTRAVI (n=575) or placebo (n-577).¹  Thrombocytopenia was identified as an AE of special interest. Additionally, platelet count was monitored for the duration of the study.² 

The median duration of study treatment was 70.7 weeks and 63.7 weeks for subjects who received UPTRAVI or placebo, respectively.¹The Table: Frequency of Thrombocytopenia-related AEs, as Reported in GRIPHON provides safety data from GRIPHON relating to AEs denoting thrombocytopenia.³ 

SAEs denoting thrombocytopenia were reported in 2 patients (<1%) on UPTRAVI compared with no patients on placebo during GRIPHON. There were no discontinuations or deaths due to thrombocytopenia-related AEs during GRIPHON.⁴ 

Treatment-emergent platelet count abnormalities in hematology tests in GRIPHON

The proportion of patients who had either a marked decrease in platelet count (defined as <75 GI/L) or an alert decrease (defined as <50 GI/L) was similar for both groups.^2,4  Please see Table: Treatment-emergent Platelet Count Abnormalities in Hematology Tests in GRIPHON.^2,4 

Treatment-emergent Platelet Count Abnormalities in Hematology Tests in GRIPHON^2,4 

GRIPHON OL Study

GRIPHON OL (AC-065A303) was an open-label, multicenter study that aimed to assess the long-term safety and tolerability of UPTRAVI in patients with PAH. Patients enrolled in GRIPHON were eligible to enter the GRIPHON OL study either after experiencing a morbidity event during the double-blind treatment or at end of the study if they were still receiving the study treatment.⁵ 

Safety Results

Of the 709 patients on UPTRAVI during the OL period, SAEs of thrombocytopenia and immune thrombocytopenic purpura were reported in 2 (0.28%) patients and 1 (0.14%) patient, respectively.⁶ 

Literature Search

A literature search of MEDLINE^®, Embase, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on the 17 June 2025.