Patients with PAH show more benefit with seralutinib if deemed responders
Key takeaways:
- The classification of “responder” was earned by achieving a decrease in pulmonary vascular resistance greater than 15% by week 72 of seralutinib.
- This subgroup had larger changes from baseline in cardiac output.
Among patients with pulmonary arterial hypertension treated with 72-week seralutinib, those deemed responders had more improved measures, according to a poster presented at the Pulmonary Vascular Research Institute 2025 Annual Congress.
As Healio previously reported, the randomized, double-blind, placebo-controlled, multicenter phase 2 TORREY study showed that seralutinib (Gossamer Bio) reduced pulmonary vascular resistance (PVR) over 24 weeks in adults with PAH.
Further, PVR continued to go down with seralutinib between 24 weeks and 72 weeks in an open-label extension study of TORREY.
In this post-hoc analysis of the above open-label extension study, Raymond L. Benza, MD, professor and system director of pulmonary hypertension at Icahn School of Medicine at Mount Sinai, and colleagues evaluated 28 patients with PAH who received twice-daily 90 mg inhaled seralutinib for 72 weeks to gain additional insight on the impact of the treatment in this specific population.
In terms of PVR improvement, the poster reported that 20 patients experienced this outcome (median change in total cohort, –23.3%).
Within this cohort, 17 patients earned the classification of “responders” by achieving a decrease in PVR greater than 15% by the 72-week mark (median change, –32%; range, –17% to –62%), according to researchers.
Additionally, a change in PVR to less than 200 dyne*s/cm5 at week 72 was identified in three patients.
Between the total group and the responder subgroup, researchers observed larger median changes from baseline to week 72 among the responder patients when assessing cardiac output (19.6% vs. 1.8%) and mean pulmonary arterial pressure (–11.8% vs. –7.7%).
This pattern continued to be found during the evaluation of 6-minute walk distance, with a larger mean change from baseline reported in the responder subgroup vs. the total group (38.6 m vs. 29.8 m), according to the poster.
Based on treatment-emergent adverse event findings, researchers noted “no new safety signals emerging over the [open-label extension] treatment period to date.” Frequent treatment-emergent adverse events in both the total group and the responder subgroup included COVID-19 (28.6% vs. 23.5%), headache (25% vs. 29.4%), epistaxis (21.4% vs. 23.5%) and nausea (21.4% vs. 17.6%).
“Acknowledging the limitations of an open-label study and post-hoc analysis, longer-term treatment with seralutinib resulted in continued PVR improvement through 72 weeks of treatment in a low-risk, heavily treated population,” Benza and colleagues wrote.
Perspective
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In this study, Benza and colleagues present the findings of an open-label extension of the phase 2 TORREY study investigating the long-term effects of seralutinib in patients with PAH. Seralutinib, a novel inhaled agent targeting platelet-derived growth factor receptor and other key pathways, is currently in phase 3 clinical trials for treatment of PAH. The open-label extension examined the impact of seralutinib on hemodynamics and exercise capacity after 72 weeks of treatment.
Although the overall sample size of patients was small, 20 out of 28 patients showed improvements in PVR at 72 weeks and 17 out of 28 patients were classified as responders, defined by a greater than 15% reduction in PVR from baseline. Three patients, albeit a small subset, achieved near normalization of PVR (< 200 dynes), a remarkable degree of improvement that is not commonly achieved in clinical practice. Improvements in PVR were driven by improvements in both mean pulmonary arterial pressure and cardiac output and were also associated with improved exercise capacity.
For a progressive disease typically characterized by worsening over time, the fact that PVR improvements were sustained at 72 weeks, closely matching the results at 24 weeks, is impressive, particularly for patients already on background therapy, although details regarding escalation of other therapies are not reported. Reassuringly, there were also no new safety concerns in this long-term open-label extension study.
These results contribute valuable insights into the long-term effects of seralutinib and highlight its potential as a therapeutic option in PAH. The future of PAH treatment appears increasingly promising, with new agents targeting novel pathways on the horizon. As PAH therapeutic regimens become more complex and personalized medicine advances, further research is needed to better understand the subset of “responders.” The results of the ongoing phase 3 PROSERA study are also eagerly awaited by the PH community.
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Benza RL, et al. Sustained benefit with seralutinib treatment: A post-hoc analysis of the TORREY open-label extension. Presented at: Pulmonary Vascular Research Institute 2025 Annual Congress; Jan. 29-Feb. 1, 2025; Rio de Janeiro.