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Efficacy, Safety, and Pharmacokinetics of Macitentan in Japanese Pediatric Patients With Pulmonary Arterial
Ryo Inuzuka1, Taku Ishii2, Toru Iwasa3
1Department of Pediatrics, The University of Tokyo Tokyo Japan.
Insights
Macitentan effectively reduced pulmonary vascular resistance and improved hemodynamics in pediatric pulmonary arterial hypertension (PAH) patients. The study demonstrated a favorable safety profile over 52 weeks in this young population.
Area of Science:
- Pediatric Cardiology
- Pulmonary Hypertension Research
- Pharmacology
Background:
- Pulmonary arterial hypertension (PAH) involves elevated pulmonary arterial pressure and resistance, straining the right ventricle and potentially causing heart failure.
- Macitentan, a dual endothelin receptor antagonist, is approved for adult PAH but has limited data in pediatric cases.
Purpose of the Study:
- To evaluate the efficacy and safety of macitentan in Japanese pediatric patients with PAH.
- To assess the impact of macitentan on pulmonary hemodynamics and functional outcomes in children with PAH.
Main Methods:
- An open-label, multicenter, Phase III study included 7 Japanese pediatric PAH patients (3 months to <15 years).
- Efficacy was measured by pulmonary hemodynamics at 24 weeks; safety was monitored over 52 weeks.
Main Results:
- The primary endpoint, a reduction in pulmonary vascular resistance index (PVRI) by 59.43% at 24 weeks, met the success criterion.
- Improvements were observed in other hemodynamic parameters, including mean pulmonary arterial pressure and total pulmonary resistance.
- Functional outcomes showed a trend toward improvement, and macitentan exhibited a favorable safety profile with no unexpected adverse events.
Conclusions:
- Macitentan demonstrated clinically significant PVRI reduction and improved pulmonary hemodynamics in pediatric PAH patients.
- The drug was well-tolerated over 52 weeks, indicating a favorable safety profile for this population.
Background:
Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), imposing an increased workload on the right ventricle and ultimately leading to right heart failure. Macitentan is a potent dual endothelin receptor antagonist that blocks both endothelin receptor subtypes A and B, and is approved for adult patients with PAH, but evidence in pediatric PAH patients is limited.
Methods And Results:
This was an open-label, multicenter, Phase III study enrolling Japanese pediatric PAH patients aged ≥3 months to <15 years. A total of 7 patients were enrolled. Efficacy was evaluated by assessing pulmonary hemodynamics after 24 weeks of treatment, and safety was assessed over a 52-week period. The geometric mean fold change in PVR index (PVRI) at Week 24 was 59.43%, which met the prespecified success criterion of ≤81.6% (primary endpoint). Other pulmonary hemodynamic parameters, including mean PAP, mean right atrial pressure, and total pulmonary resistance, also showed improvement. Additionally, at Week 52, functional outcomes such as 6-minute walk test performance and quality-of-life reports, demonstrated a trend toward improvement. Safety findings were favorable, with no unexpected concerns among the 7 treated participants. Most adverse events were mild to moderate in severity, and none were considered related to macitentan.
Conclusions:
Macitentan showed clinically meaningful reduction in PVRI and improved pulmonary hemodynamics in Japanese pediatric patients with PAH, with a favorable safety profile over 52 weeks of treatment.
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