Fact checked byKristen Dowd

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June 03, 2024
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Combination macitentan, tadalafil tablet improves exercise capacity in PAH

Fact checked byKristen Dowd
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Key takeaways:

  • A prior study found that a combination macitentan and tadalafil tablet increased 6-minute walk distance at 16 weeks.
  • As time progressed, the improvement in exercise capacity from baseline grew larger.

SAN DIEGO — Exercise capacity improved among adults with pulmonary arterial hypertension taking a macitentan-tadalafil tablet over 68 weeks, according to research presented at the American Thoracic Society International Conference.

Opsynvi (Johnson & Johnson), a once-daily tablet that includes 10 mg macitentan and 40 mg tadalafil, was recently approved by the FDA to treat adults with PAH, according to a manufacturer-issued press release.

Infographic showing mean change in 6MWD from baseline of the A DUE double-blind period.
Data were derived from Chin KM, et al. Effect on exercise capacity and long-term safety and tolerability of macitentan and tadalafil as a single-tablet combination in patients with pulmonary arterial hypertension from the A DUE open-label interim analysis. Presented at: American Thoracic Society International Conference; May 17-22, 2024; San Diego.

The approval was based, in part, on data from the randomized, active-controlled, multicenter, adaptive parallel-group, phase 3 A DUE study of 187 adults with PAH who either received Opsynvi, tadalafil alone or macitentan alone.

Researchers of this study found that from baseline to 16 weeks, the combination tablet lowered pulmonary vascular resistance more than tadalafil or macitentan alone.

In an interim analysis of the A DUE study 24-month open-label period, Kelly M. Chin, MD, professor of internal medicine and director of pulmonary hypertension clinical research at University of Texas Southwestern Medical Center, and colleagues assessed 107 adults with PAH given the macitentan-tadalafil tablet in both the 16-week double-blind period and the open-label period to determine how the drug impacts 6MWD at 6 and 12 months.

As time progressed, researchers observed larger improvements in 6MWD from the baseline measure recorded at the start of the double-blind period. At 16 weeks (n = 94), the mean change was 50 m, which increased to 59.5 m at week 42, or the 6-month mark of the open-label (n = 75). By week 68, or the 12-month mark of the open-label (n = 51), 6MWD improved by 71.8 m from baseline.

Researchers also captured long-term safety of the drug combination in a cohort of 185 patients, which included patients who received the drug in the double-blind period and patients who started receiving it during the open-label period.

Many patients experienced at least one adverse event (91.9%), whereas fewer patients reported one or more serious adverse events (24.3%).

An adverse event was the reason behind why 17 patients (9.2%) stopped taking the fixed-dose drug combination, according to researchers.

Researchers noted four adverse events of special interest and found that 41 patients (22.2%) experienced anemia and 32 patients (17.3%) experienced edema and fluid retention. The remaining two adverse events occurred less frequently: Hypotension (n = 12; 6.5%) and hepatic disorders (n = 9; 4.9%).

Six patients had liver abnormalities indicated by a minimum aspartate transaminase/alanine transaminase ratio of three multiplied by the upper limit of normal (3.4%). Further, four patients (2.3%) met the threshold signaling low hemoglobin (< 8 g/dL).

None of the five reported deaths were related to the study drug, according to researchers.

Researchers attributed deaths to gastroenteritis clostridial, cardiac failure, right ventricular failure, COVID-19 pneumonia and cerebrovascular accident.

Notably, three deaths were treatment-emergent, occurring up until 30 days after treatment, whereas the remaining two took place more than 30 days after.

“Long-term safety/tolerability of [macitentan tadalafil fixed-dose combination] in the open label period was comparable with that seen in the A DUE double-blind period; no new or unexpected safety concerns were revealed,” Chin and colleagues wrote.

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