• Seralutinib’s inhalation-based delivery precisely targets deep lung tissues, tackling the root causes of pulmonary arterial hypertension (PAH) while minimizing systemic exposure. This method offers potent therapeutic effects directly to the affected area, potentially mitigating systemic side effects and enhancing treatment efficacy.
• Interim results from the TORREY open-label extension study demonstrate sustained improvements in pulmonary vascular resistance (PVR) and exercise capacity over 72 weeks with seralutinib treatment, highlighting its potential as a long-term therapy for pulmonary arterial hypertension (PAH).

Gossamer Bio presented promising updates on their drug candidate, seralutinib, at the American Thoracic Society 2024 International Conference in San Diego, California, held from May 17 to 22, 2024. The poster, titled “Interim Results from the Phase Ib and Phase II TORREY Open-label Extension Study of Seralutinib in Pulmonary Arterial Hypertension (PAH)”, featured interim results from the TORREY open-label extension study, highlighting the potential of seralutinib as a treatment for PAH.

Pulmonary Arterial Hypertension (PAH) is a rare and progressive disorder characterized by high blood pressure in the lungs’ arteries. According to the DelveInsight PAH forecast report, in 2023, over 53 million people across the 7MM are diagnosed with PAH, with a higher prevalence among females. While current treatments aim to dilate blood vessels and reduce pressure, they often fall short due to disease progression, side effects, and limited access, highlighting substantial unmet needs.

Seralutinib is a novel, potent tyrosine kinase inhibitor (TKI) targeting PDGFR, CSF1R, and c-KIT. Unlike oral imatinib, which faced safety concerns in the IMPRES PAH trial, seralutinib is specifically designed for inhalation, allowing direct delivery to deep lung tissues. This formulation aims to maximize therapeutic effects while minimizing systemic exposure and side effects. Seralutinib targets pathways contributing to proliferation, inflammation, and fibrosis, which are key drivers of pulmonary vascular remodeling in PAH.

In the Phase II TORREY study (NCT04456998), inhaled seralutinib met its primary endpoint by significantly reducing pulmonary vascular resistance (PVR). Patients completing TORREY had the option to enroll in an open-label extension (OLE) study (NCT04816604). The interim results as of March 4, 2024, included 73 (of 80) patients from the TORREY study and 1 (of 8) patient from a Phase Ib study (NCT03926793), all receiving 90 mg of inhaled seralutinib twice daily.

Study Methods and Patient Demographics: The primary aim of the OLE study was to evaluate long-term safety and tolerability, with efficacy parameters such as hemodynamics assessed at Week 72. PVR was measured via right heart catheterization. At OLE entry, 34 patients continued on seralutinib (continued-seralutinib group), while 40 switched from placebo to seralutinib (placebo-crossed group). Baseline characteristics showed a mean age of 42 years and varied durations since PAH diagnosis, with the majority on double or triple therapy.

Key Results: From Week 24 to Week 72, a notable decrease in median pulmonary vascular resistance (PVR) was observed in both the continued-seralutinib and placebo-crossed groups. In the continued-seralutinib group, the median PVR changed from 505.0 dynes sec/cm5 at Week 24 to 457 dynes sec/cm5 at Week 72, representing a reduction of 5.9%. Similarly, in the placebo-crossed group, the median PVR changed from 647 dynes sec/cm5 at Week 24 to 603 dynes sec/cm5 at Week 72, indicating a reduction of 6.8%. These reductions suggest sustained treatment effects and hint at the potential long-term benefits of seralutinib for patients with Pulmonary Arterial Hypertension (PAH).

Exercise capacity, measured by the 6-minute walk distance (6MWD), improved in both groups over the 72 weeks. The continued-seralutinib group and the placebo-crossed group showed favorable changes, underscoring the drug’s efficacy.

Safety and Tolerability: Seralutinib was well-tolerated, with no new safety signals identified during the OLE treatment period, which extended up to 2.4 years. The incidence of treatment-emergent adverse events (TEAEs) was consistent with previous findings, with the most common TEAEs being headache (25.7%), cough (24.3%), and COVID-19 (23.0%). The frequency of hepatic enzyme elevations was similar between the OLE and TORREY studies.

Conclusion: The open-label extension data for seralutinib demonstrate a promising long-term efficacy profile, with continued improvements in PVR and exercise capacity up to 72 weeks. 

Seralutinib’s targeted inhalation delivery system presents a significant advantage in the treatment of Pulmonary Arterial Hypertension (PAH), effectively addressing the underlying pathological mechanisms while maintaining a favorable safety profile. These findings underscore the importance of further advancing seralutinib as a novel anti-proliferative therapy for PAH. The ongoing Phase III PROSERA study (NCT05934526) is actively enrolling participants to comprehensively assess the efficacy and safety of seralutinib in PAH patients.

Furthermore, Seralutinib’s unique ability to penetrate deep lung tissues via dry powder inhalation offers a convenient and potentially transformative approach to PAH treatment. By directly targeting the underlying pathological remodeling mechanisms of the disease, it distinguishes itself from current vasodilatory therapies. These characteristics position seralutinib as a promising candidate for addressing the complex needs of PAH patients, providing hope for improved outcomes and enhanced quality of life.