A new analysis of Actelion‘s GRIPHON clinical trial indicates that Uptravi (selexipag) tablets reduce the risk of disease complications or death in patients with pulmonary arterial hypertension (PAH), regardless of when treatment begins. However, its effectiveness was greater if started sooner after diagnosis.
The data was presented at the 2019 American Thoracic Society (ATS) International Conference, held May 17-22 in Dallas, Texas, in a poster titled “The Impact of Time from Diagnosis at Baseline on Long-Term Outcome in the GRIPHON Study: Selexipag in Pulmonary Arterial Hypertension.”
Uptravi is an oral prostacyclin receptor agonist — that is, a molecule that mimics the effects of prostacyclin. By working like prostacyclin, the medicine results in vasodilation, decreasing blood pressure and improving pulmonary blood circulation. In the U.S., Uptravi is indicated for the treatment of PAH (WHO, group 1) to delay disease progression and reduce the risk of hospitalization.
GRIPHON is a Phase 3, randomized, controlled clinical trial (NCT01106014) designed to assess Uptravi’s long-term safety and effectiveness, compared with placebo, for reducing the risk of death or PAH complications. According to Actelion, the trial was the largest randomized, controlled study ever done in PAH patients, enrolling 1,156 participants across 39 countries.
Previous trial data demonstrated that treatment with Uptravi reduced in 40% of participants the occurrence of a complication related to PAH or death, even though an effect over “all-cause” mortality alone was not demonstrated.
The latest post-hoc analysis, presented at the ATS conference, used GRIPHON’s trial data to see if the time from PAH diagnosis to beginning Uptravi had any effect on the patients’ response to the medicine.
Participants were categorized in two groups: patients treated earlier, who were defined as those who received treatment within six months from diagnosis (404 patients); and those who were treated later, who received treatment later than six months after their diagnosis (752 patients).
Results showed that, in both groups, taking Uptravi was associated with a reduction in the risk of complications or death, compared with placebo. However, the risk reduction was more pronounced in those treated earlier, than in those treated later — specifically 55% versus 30%.
This tendency was maintained irrespective of the background therapy (other PAH treatments) taken by patients.
“Consistent with other studies suggesting that earlier initiation of treatment for PAH results in a more pronounced treatment effect, this analysis shows that outcome was better in patients who were treated with selexipag [Uptravi] closer to the time of diagnosis,” researchers wrote.
Sean Gaine, MD, director of National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland, and the presenter of the data at ATS, said in a press release: “This new analysis reinforces the overall efficacy data for selexipag and provides compelling evidence of the benefits of initiating selexipag early. 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 five years of diagnosis.”
“Early recognition and prompt treatment of the disease are key to achieving sustained long-term benefits,” Gaine added.
According to Richard Channick, MD, professor and director of the acute and chronic thromboembolic disease program at UCLA Medical Center, who also was involved in the study, GRIPHON data “firmly established the importance of the prostacyclin pathway in PAH treatment which will, hopefully, benefit patients worldwide.”
“This post-hoc analysis of the GRIPHON study adds to the growing body of research which indicates that selexipag can have a significant impact on a patients’ morbidity and disease progression, irrespective of background therapy,” said Alessandro Maresta, MD, vice president and head of medical affairs at Actelion.