In patients with pulmonary arterial hypertension (PAH), treatment with a fixed-dose combination of macitentan and tadalafil was associated with significant improvements in pulmonary hemodynamics compared to monotherapy, according to study results presented at the American College of Cardiology’s 72nd Annual Scientific Session & Expo Together With World Congress of Cardiology, held March 4-6, 2023, in New Orleans, Louisiana.

The phase 3 A DUE study (NCT03904693) was conducted to evaluate treatment with an investigational, once-daily, single-tablet combination of macitentan (10 mg) and tadalafil (40 mg) (M/T STCT), compared with macitentan and tadalafil monotherapies, in patients with PAH and World Health Organization (WHO) functional class (FC) II or III.

Recently updated guidelines from the European Society of Cardiology/European Respiratory Society (ESC/ERS) have reinforced recommendations on the use of initial dual combination therapy in patients with PAH who have no cardiopulmonary comorbidities. M/T STCT is the first single tablet to target 2 or more PAH-specific pathways.

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“Targeting different pathways in the treatment of PAH has demonstrated clear clinical benefits, yet current treatment regimens are cumbersome and create a significant pill burden for patients, many of whom take a large number of pills each day to treat their PAH and various comorbidities,” said Kelly Chin, MD, professor of internal medicine and director of the Pulmonary Hypertension Program at the University of Texas Southwestern Medical Center in Dallas and an investigator in the A DUE study.

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Reductions in pill/tablet count and frequency of administration can have a major impact on adherence to treatment, which, in turn, can influence clinical outcomes.

The investigators of the multicenter, double-blind, randomized, active-controlled, adaptive parallel-group A DUE study sought to compare the efficacy and safety of investigational M/T STCT with those of macitentan and tadalafil monotherapies in individuals with PAH.

A DUE enrolled 187 adults with PAH from 148 sites in 19 countries who were in WHO FC II or III and were treatment- naïve or being treated with a stable dose of an endothelin receptor antagonist (ie, macitentan) or a phosphodiesterase type 5 inhibitor (ie, tadalafil) for 3 months or longer.

The primary endpoint was pulmonary vascular resistance, which was measured at 16 weeks following treatment initiation. Among the secondary endpoints was change from baseline in exercise capacity, as determined by the change in 6-minute walk distance (6MWD) from baseline at week 16. After the double-blind treatment phase, participants transitioned to the open-label treatment period for 24 months.

The A DUE study fulfilled its coprimary endpoint, with statistically significant improvements in pulmonary hemodynamics demonstrated (P <.0001) over both monotherapies. Although not statistically significant, a clinically relevant improvement in 6MWD was reported with M/T STCT vs monotherapy.

“The guiding light of our [pulmonary hypertension] research is the goal of transforming PAH into a manageable condition, so we’re constantly looking for ways to improve both clinical outcomes and the treatment experience,” said James List, MD, PhD, global therapeutic area head of cardiovascular, metabolism, retina, and pulmonary hypertension at Janssen Research & Development, the pharmaceutical company developing the fixed-dose combination therapy.


Late-breaking phase 3 A DUE data show investigational single-tablet combination therapy of macitentan and tadalafil significantly improves pulmonary haemodynamics versus monotherapy in patients with pulmonary arterial hypertension (PAH). News release. Janssen Pharmaceutica NV; March 6, 2023.