Early initiation of selexipag results in more pronounced treatment effect: GRIPHON

DALLAS — In a post hoc exploratory analysis of the GRIPHON study, treatment with selexipag, compared with placebo, improved clinical outcomes in patients with peripheral artery hypertension regardless of time from diagnosis to treatment initiation, with a more pronounced treatment effect in patients who received selexipag soon after diagnosis.

The GRIPHON study evaluated long-term efficacy and safety of oral selexipag (Uptravi, Actelion Pharmaceuticals/Johnson & Johnson) in 1,156 patients with PAH in 39 countries. In the overall trial, the primary composite endpoint of morbidity and mortality was reduced by 40% with selexipag compared with placebo. The composite endpoint included progression or worsening of PAH leading to hospitalization, long-term oxygen therapy, initiation of IV prostanoid therapy, need for lung transplant or balloon atrial septostomy or death from any cause.

The new post hoc analysis, presented at the American Thoracic Society International Conference, evaluated the effect of time from diagnosis to initiation of selexipag based on treatment response with respect to the primary endpoint. At baseline, patients enrolled in GRIPHON were categorized based on time from diagnosis to treatment: within 6 months of PAH diagnosis (n = 404) or after 6 months of diagnosis (n = 752), according to a company press release.

Compared with placebo, selexipag reduced the risk for morbidity and mortality in both groups. The risk reduction was 55% among patients who received treatment within 6 months of a diagnosis (HR = 0.45; 95% CI, 0.33-0.63) and 30% among those who received treatment later (HR = 0.7; 95% CI, 0.54-0.91). Treatment response was more pronounced in patients who received earlier treatment, according to the ATS 2019 abstract.

This pattern was observed in all background PAH therapy subgroups, according to the researchers.

“The GRIPHON study firmly established the importance of the prostacyclin pathway in PAH treatment, which will, hopefully, benefit patients worldwide,” Richard Channick, MD, professor of medicine and director of the Acute and Chronic Thromboembolic Disease Program at UCLA Medical Center, stated in the release. “This new analysis clearly demonstrates that early treatment is crucial if we are to significantly improve long-term outcomes in this serious, progressive disease.”

Patients treated with selexipag within 6 months of a diagnosis were younger and more likely to be in WHO functional class II, treatment naive and live in Asia or Eastern Europe compared with patients treated later, according to the abstract.

“This new analysis reinforces the overall efficacy data for selexipag and provides compelling evidence of the benefits of initiating selexipag early,” Sean P. Gaine, MD, consultant respiratory physician and director of the National Pulmonary Hypertension Unit at Mater Misericordiae University Hospital in Dublin, stated in the release. “These data add to the growing evidence supporting early intensification of treatment, which is important when you consider that around a third of PAH patients currently die within 5 years of diagnosis. Early recognition and prompt treatment of the disease are key to achieving sustained long-term results.”

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Selexipag is an oral IP prostacyclin receptor agonist. In the United States, selexipag is FDA approved for the treatment of PAH to delay disease progression and reduce the risk for hospitalization. – by Katie Kalvaitis

Reference:

Gaine SP, et al. A2502/101. Glory Days: The Latest Clinical Research in PAH. Presented at: American Thoracic Society International Conference; May 17-22, 2019; Dallas.

Disclosures: Channick and Gaine have received research support and served as paid consultants to Actelion.