Janssen’s single tablet combination shows promise in phase 3 PAH study

The Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) have announced positive results from a phase 3 trial of an investigational single tablet combination therapy of macitentan and tadalafil in pulmonary arterial hypertension (PAH) patients.

PAH is a rare, progressive and life-threatening blood vessel disorder characterised by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation, resulting in a significant strain on the heart.

An estimated 500 to 1,000 new cases of PAH are diagnosed each year in the US, with the condition most common in women between the ages of 30 and 60.

A dual combination therapy with macitentan and tadalafil has recently been recommended for patients without cardiopulmonary comorbidities, but this currently requires patients to take multiple pills.

“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,” explained Kelly Chin, professor of internal medicine and director of the pulmonary hypertension programme at UT Southwestern Medical Center, and an investigator in the A DUE study.

The results from Janssen’s A DUE study, presented at the American College of Cardiology, demonstrate significant improvements with the company’s single tablet combination compared to macitentan and tadalafil monotherapies.

A total of 187 adult PAH patients worldwide, in World Health Organization functional class two or three who were treatment naïve or on a stable dose of an endothelin receptor antagonist or a phosphodiesterase type 5 inhibitor for at least three months, were enrolled in the study.

The co-primary endpoint of the trial was met, demonstrating marked pulmonary haemodynamic improvement as shown by the highly statistically significant, consistent and robust pulmonary vascular resistance reduction in patients treated with the single table combination.

Secondary efficacy outcome measures included change from baseline in exercise capacity, as measured by change in six-minute walk distance (6MWD). Despite treatment effect not being statistically significant at week 16, a clinically relevant improvement in 6MWD in favour of Janssen’s single tablet combination was observed.

“The results from this study demonstrate that a single tablet combination has the potential to support initial dual combination therapy and rapid escalation from monotherapy, which may improve functional outcomes and help close the gap from guideline recommendations to clinical practice,” Chin added.