Interim Results from the Phase 1B and Phase 2 TORREY Open-label Extension Study of Seralutinib in Pulmonary Arterial Hypertension (PAH)

Seralutinib is a highly potent inhibitor of PDGFRα/ß, CSF1R, and c-KIT kinase pathways driving vascular remodeling in PAH. The phase 2 TORREY study in PAH (NCT04456998) met its primary endpoint of reduction in pulmonary vascular resistance (PVR) from baseline (BL) to Week (W) 24 (-14.3%; p=0.0310). We present interim results (as of Oct 26, 2023) from an OLE study (NCT04816604) to evaluate seralutinib’s long-term safety, tolerability and efficacy.

73/80 patients from TORREY (WHO Group 1 PH on stable PAH-specific background medications) and 1/8 patients from a phase 1B study (NCT03926793) enrolled and received seralutinib 90mg BID by dry powder inhaler. The primary endpoint was safety and tolerability; treatment-emergent adverse events (TEAEs) were recorded. PVR was measured at TORREY BL and OLE W24 and W72. Analyses are descriptive.

At OLE entry (OE), 34 patients continued seralutinib (S–S) and 40 switched from placebo to seralutinib (P–S), mean age 50 years, 89.2% female. WHO FC I/II/III/IV for S–S, 5.9%/76.5%/17.6%/0; P–S, 7.5%/45%/40%/7.5%. 37.8%/56.8% had 2/3 background PAH medications. Most common TEAEs were headache (24.3%), COVID-19 (23%) and cough (21.6%). Cough was less frequent in the OLE (W72: S–S 20.6%; P–S 22.5%) than in TORREY: seralutinib 43.2%; placebo 38.1%). TEAEs led to study discontinuation in 18 (24.3%) patients, most due to cough. 2 patients discontinued seralutinib (1/group) for increased ALT/AST, resolving upon discontinuation. 3 deaths occurred, unrelated to seralutinib. At OE, median PVR was higher in the P–S vs S-S group (Table). From W24-W72, median PVR change was similar in both groups. Overall, 73% S-S and 75% P-S patients improved or maintained PVR at W72.

Seralutinib was well tolerated for up to 72 weeks. No new safety signals were identified. Further PVR reductions from W24-W72 with S–S suggest treatment effect persistence. PVR improved with P–S for≤48 weeks. A phase 3 study of seralutinib in PAH is enrolling (PROSERA, NCT05934526).

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Artikel online veröffentlicht:
18. März 2025