The following is a summary of “Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH),” published in the January 2023 issue of Pulmonology by Bajwa, et al.
For a study, researchers sought to address the persistently high rates of morbidity and death, novel treatments for pulmonary arterial hypertension (PAH) are required with improved safety/tolerability profiles.
Using a dry-powder inhaler device, the novel small-molecule activator of soluble guanylate cyclase MK-5475 was tested in Phase 1 research to determine its effectiveness and safety in PAH patients. Participants with a PAH diagnosis, a BMI of ≤35 kg/m2, and an age range of 18 to 70 were eligible (Group 1 pulmonary hypertension). Participants in Part 1 underwent double-blind safety testing with MK-5475 or a placebo (primary outcome). Four panels took part in ≤3 open-label periods in Part 2. Safety/tolerability was evaluated in Part 2/Period 1. Functional respiratory imaging was used to measure the pulmonary blood volume (a secondary outcome), and right cardiac catheterization was used to measure the pulmonary vascular resistance in Part 2/Periods 2 and 3, respectively (primary outcome).
Up to 24 hours after the dosage, MK-5475 was typically well tolerated with no systemic adverse effects on blood pressure or heart rate. Regarding the main pharmacodynamic result, mean decreases in pulmonary vascular resistance between 120 μg and 360 μg dosages varied from 21% to 30%.
Pulmonary vascular resistance was rapidly and persistently reduced after treatment with inhaled single-dose MK-5475, and pulmonary blood volume was increased. MK-5475 was usually well tolerated compared to the placebo and had no vasodilatory systemic adverse effects. The basis for continued clinical development is laid by MK-5475’s encouraging pulmonary selectivity and acceptable safety/tolerability profile, as seen in the research of adult patients with PAH.