Inhaled seralutinib reduces vascular resistance in patients with PAH over 72 weeks
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Key takeaways:
- A previous study found that seralutinib lowered pulmonary vascular resistance over 24 weeks.
- Pulmonary vascular resistance continued to improve with seralutinib treatment between 24 weeks and 72 weeks.
SAN DIEGO — Among patients with pulmonary arterial hypertension, seralutinib lowered pulmonary vascular resistance over 72 weeks, according to research presented at the American Thoracic Society International Conference.
This study was led by Olivier Sitbon, MD, PhD, professor of respiratory medicine at Université Paris-Saclay and consultant at the French Referral Center for Pulmonary Hypertension in the department of respiratory and intensive care medicine at Hôpital Bicêtre in Le Kremlin-Bicêtre, France.
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 pulmonary arterial hypertension.
In an open-label extension study of TORREY, Sitbon and colleagues assessed 73 patients with PAH from the phase 2 study and one patient from a phase 1B study (total, n = 74; mean age, 50 years; 89.2% women) to see if twice-daily 90 mg inhaled seralutinib was safe and effective in terms of PVR over 72 weeks.
Notably, the cutoff date for these interim results was Oct. 26, 2023.
Although every patient in this extension study received seralutinib, 40 of the included patients received placebo during the TORREY study (placebo-to-seralutinib), whereas the remaining 34 patients received seralutinib (seralutinib-to-seralutinib).
Most of the patients in the continued seralutinib group belonged to WHO FC II (76.5%), followed by FC III (17.6%) and FC I (5.9%). In the placebo-to-seralutinib group, most patients either belonged to WHO FC II (45%) or FC III (40%), with fewer patients in FC I (7.5%) and FC IV (7.5%).
Between the two cohorts, researchers observed a greater proportion of patients on two of three PAH-specific background medications in the placebo-to-seralutinib group vs. the continued seralutinib group (56.8% vs. 37.8%).
In terms of treatment-emergent adverse events, patients frequently reported headaches (24.3%), COVID-19 and cough (both 21.6%).
At week 24 in the TORREY phase 2 study, 43.2% of those receiving seralutinib and 38.1% of those receiving placebo reported cough. Compared with these percentages, researchers noted that cough occurred less frequently in both the continued seralutinib group (20.6%) and the placebo-to-seralutinib group (22.5%) at week 72.
Of the total cohort, 18 patients discontinued seralutinib due to a treatment-emergent adverse event. Researchers found that cough was often the event behind discontinuation, but for one patient in each of the groups, the reason for discontinuation was heightened aspartate transaminase/alanine transaminase.
None of the reported deaths (n = 3) were related to the study drug, according to researchers.
By week 72, researchers had data for 26 patients in the continued seralutinib group and 24 patients in the placebo-to-seralutinib group.
Median PVR in the placebo-to-seralutinib group (644.5 dyne*s/cm5) was higher than the median in the continued seralutinib group (500 dyne*s/cm5) when assessed at the start of the extension study.
Researchers evaluated median changes in PVR from week 24 to week 72 and from the baseline of the TORREY study to week 72.
In the continued seralutinib group, PVR decreased by 47.5 dyne*s/cm5 (–9.1%) between week 24 and week 72. A similar reduction was observed in the placebo-to-seralutinib group during this 48-week timeframe (–47 dyne*s/cm5; –7.3%).
More patients in the continued seralutinib group vs. the placebo-to-seralutinib group had PVR that improved by at least 10% (n = 15; 57.7% vs. n = 11; 45.8%), according to researchers.
Considering a longer timeframe, researchers found a large reduction in PVR among patients in the continued seralutinib group between TORREY baseline and week 72 (143 dyne*s/cm5; –23.6%). For patients in the placebo-to-seralutinib group, PVR decreased by 71 dyne*s/cm5 (–10.5%) during this timeframe.
“Further reductions from week 24 to week 72 in PVR demonstrated by seralutinib-to-seralutinib patients suggest persistence of treatment effect,” Sitbon and colleagues wrote.
According to the abstract, further research on seralutinib is underway in the phase 3 PROSERA study.