24-Month Findings on Macitentan, Tadalafil for Pulmonary Arterial Hypertension, with Kelly Chin, MD

Positive findings have been released from the 24-month open-label extension of the A DUE trial, evaluating a macitentan and tadalafil fixed-dose combination treatment (OPSYNVI) in a single-tablet for patients with pulmonary arterial hypertension (PAH).1

These long-term, late-breaking findings were presented at the American Thoracic Society (ATS) International Conference. Kelly Chin, MD, lead investigator and professor of Internal Medicine and Director of Pulmonary Hypertension Clinical Research at UT Southwestern Medical Center, spoke with HCPLive about the findings and their significance for PAH.

“Pulmonary hypertension is a deadly disease, and these were fairly large improvements that we were seeing for the study, and I think that's something that we are seeing with combination therapy in general,” Chin said. “And there has been a move towards giving the vast majority of patients upfront combination therapy, from the get-go, and we're seeing reductions in hospitalizations, reductions in mortality, and observational data, and so on. From a single tablet standpoint, I think it improves adherence.”

In looking at the long-term impact of a macitentan and tadalafil fixed-dose combination on overall drug survival, reduction of cardiac biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP), hospitalizations, exercise capacity, and safety, several key findings were uncovered.

Specifically, patients being treated with the macitentan/tadalafil fixed-dose combination (M/T FDC) therapy were shown to have a 91% survival rate at 24 months and there were sustained clinical improvements in exercise capacity and NT-proBNP levels.1 Rates of hospitalization also remained low, and the medication showed a consistent safety profile with no new safety concerns over the long term.

Chin was asked about her perspective on safety and side effects in using the treatment.

“Both medications have potential side effects, and we have to watch for those,” Chin explained. “When you have two tablets together, the potential for side effects is increased. Most of the adverse effects happen early on, up front, and so there's a period of time, no matter how you do it, whether it's one tablet or multiple tablets, you're going to want to be seeing patients pretty closely. Watching for things like fluid overload and checking lab results.”

Chin noted that watching for anemia is often needed and that some patients report headaches that interfere with tolerability. She also touched on the significance of achieving these long-term results in an open-label extension period following a double-blind trial, especially in a progressive disease such as PAH.

For additional information from this interview, view the full video segment posted above.

The quotes contained in this summary were edited for the purposes of clarity.

References

1. Chin K, et al. Long-term Treatment of Single-tablet Combination of Macitentan and Tadalafil in Pulmonary Arterial Hypertension (PAH): Final Results From the A DUE Open-label Extension. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.