The treatment landscape of pulmonary arterial hypertension (PAH) continues to evolve rapidly with the recent international approval of sotatercept in the USA for treatment of adults with PAH. Sotatercept is a fusion protein that traps activins and growth differentiation factors, which has potential anti-remodelling properties on the pulmonary vasculature relevant to PAH pathogenesis. Concerns over systemic side-effects of PAH therapies have increased efforts towards more direct lung delivery of treatments via the inhalational route. This approach may be more favourable mechanistically by allowing for a lower administered dose direct to the pulmonary mucosa with less systemic absorption. Inhaled PAH therapies may also be more patient-friendly if accompanied by an acceptable administration schedule and side-effect profile. To this end, the phase 2 INSIGNIA-PAH trial, reported in this month's issue of the European Respiratory Journal, is a dose-finding study evaluating the efficacy of MK-5475, an inhaled soluble guanylate cyclase (sGC) stimulator, for the treatment of PAH with emphasis on the drug's safety and systemic side-effect profile [1].

随着最近美国国际批准 sotatercept 用于治疗成人 PAH 患者，肺动脉高压 （PAH） 的治疗前景继续迅速发展。Sotatercept 是一种捕获激活素和生长分化因子的融合蛋白，对与 PAH 发病机制相关的肺血管系统具有潜在的抗重塑特性。对 PAH 疗法的全身副作用的担忧增加了通过吸入途径更直接地肺部给药治疗的努力。这种方法在机制上可能更有利，因为它允许直接作用于肺粘膜的较低剂量，而全身吸收较少。如果附有可接受的给药时间表和副作用特征，吸入 PAH 疗法也可能对患者更友好。为此，本月出版的《欧洲呼吸杂志》报道的 2 期 INSIGNIA-PAH 试验是一项剂量探索研究，评估吸入性可溶性鸟苷酸环化酶 （sGC） 刺激剂 MK-5475 治疗 PAH 的疗效，重点是药物的安全性和全身副作用 [1]。