Dados do Trabalho

Título

INTERIM RESULTS FROM THE PHASE 1B AND PHASE 2 TORREY OPEN-LABEL EXTENSION (OLE) STUDY OF SERALUTINIB IN PULMONARY ARTERIAL HYPERTENSION (PAH)

Introdução

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 to Week 24 (-14.3%; p=0.0310).

Objetivo

We present interim results (as of Oct 26, 2023) from an OLE study (NCT04816604) to evaluate seralutinib’s long-term safety, tolerability and efficacy.

Método

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 Week 24 and Week 72. Analyses are descriptive.

Resultados

At OLE entry, 34 patients continued seralutinib (S–S) and 40 switched from placebo to seralutinib (P–S), average age 50 years, 89.2% female. WHO FC I/II/III/IV for S–S, 5.9%/76.5%/17.6%/0; for P–S, 7.5%/45%/40%/7.5%. 37.8%/56.8% were on 2/3 PAH-specific background medications, respectively.
Most common TEAEs were headache (24.3%), COVID-19 (21.6%), and cough (21.6%). Cough incidence was lower in the OLE (Week 72: S–S 20.6%, P–S 22.5%) than in the TORREY phase 2 study (Week 24: 43.2% seralutinib and 38.1% placebo). TEAEs led to study discontinuation in 18 (24.3%) patients, most due to cough. Two patients discontinued seralutinib (one/group) for increased ALT/AST, resolving upon discontinuation. Three deaths occurred, unrelated to seralutinib.
Fifty patients reached Week 72 (S–S, n=26; P–S, n=24). At OLE initiation, median PVRs were: S–S, 500.0 dyne*s/cm5 and P–S, 644.5 dyne*s/cm5. From Weeks 24 to 72, median change in the S–S group was -47.5 dyne*s/cm5 (-9.1%) and in the P–S group -47.0 dyne*s/cm5 (-7.3%), with 15 (57.7%) and 11 (45.8%), respectively, demonstrating PVR improvements ≥10%. From TORREY baseline to Week 72, median change for S–S was -143.0 dyne*s/cm5 (-23.6%) and for P–S, -71.0 dyne*s/cm5 (-10.5%).

Conclusão

Seralutinib was well tolerated for up to 72 weeks. No new safety signals were identified. Further PVR reductions from Week 24 to Week 72 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).