Post-hoc analysis of GRIPHON study for Uptravi

Actelion Pharmaceuticals has presented results of a post-hoc exploratory analysis of the GRIPHON study in patients with pulmonary arterial hypertension (PAH) showing that treatment with Uptravi (selexipag) versus placebo improved clinical outcomes regardless of the time from diagnosis to Uptravi initiation, and that the treatment effect was more pronounced in those receiving Uptravi soon after diagnosis. The GRIPHON study evaluated the long-term efficacy and safety of oral Uptravi in 1,156 patients with PAH across 181 centers from 39 countries. It is the largest randomized, controlled, outcome trial ever conducted in patients with PAH, and demonstrated a 40% reduction in the primary composite endpoint of morbidity/mortality, defined as disease progression, worsening of PAH resulting in hospitalization, initiation of intravenous [IV] prostanoid therapy or long-term oxygen therapy, or the need for lung transplantation or balloon atrial septostomy, or death from any cause. Overall, the most common adverse events for patients receiving Uptravi were headache, diarrhea, nausea, and jaw pain.

Patients were categorized at baseline based on their time from diagnosis using a six-month threshold. Patients treated earlier were defined as those who received treatment 6 months or less from diagnosis (N=404), and those who were treated later received treatment more than 6 months from diagnosis (N=752). Uptravi reduced the risk of morbidity/mortality, compared with placebo, in both groups with a risk reduction of 55% for those treated earlier (HR 0.45 [95% CI: 0.33–0.63]) and a risk reduction of 30% for those treated later (HR 0.70 [95% CI: 0.54–0.91]). The response was more pronounced in those treated earlier. This pattern was observed in all background PAH therapy subgroups. The data were presented at the annual American Thoracic Society International Conference.

Comment: In the US, Uptravi is indicated for the treatment of PAH to delay disease progression and reduce the risk of hospitalization. In Europe, Uptravi is indicated for the long-term treatment of PAH in adult patients with WHO functional class (FC) II–III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies.