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FDA Approves Single-Tablet Combination of Macitentan and Tadalafil for Pulmonary Arterial Hypertension


In clinical trials, the newly approved Opsynvi led to a greater drop in pulmonary vascular resistance after 16 weeks compared with both tadalafil and macitentan monotherapy.

Image credit: Dr_Microbe | stock.adobe.com

Image credit: Dr_Microbe | stock.adobe.com

The FDA has approved Opsynvi, a single-tablet combination of macitentan and tadalafil, for the chronic treatment of adults with pulmonary arterial hypertension (PAH).1 Macitentan is an endothelin receptor agonist (ERA) that was initially approved on October 18, 2013, to lower the risk of hospitalization and to slow disease progression in patients with World Health Organization (WHO) group I PAH, whereas Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor with indications across erectile dysfunction, benign prostatic hyperplasia, and to improve the ability of men and women with PAH to exercise.2,3

The FDA based the regulatory action on findings from the pivotal, double-blind, randomized, active-controlled, multi-center, adaptive, parallel-group, Phase III A DUE (NCT03904693) study. The trial showed Opsynvi led to a greater drop in pulmonary vascular resistance (PVR) after 16 weeks compared with both tadalafil and macitentan monotherapy.1

“Clinical guidelines recommend treating patients with initial and sequential dual-combination therapy, regardless of risk at initial diagnosis and follow-up. Historically, this required patients to take multiple pills because no single-tablet combination therapy targeting two or more pathways was available,” A DUE trial investigator Kelly Chin, MD, professor of Internal Medicine and Director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, said in a press release. “As administration of macitentan and tadalafil together are commonly prescribed for initial therapy for PAH, the introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice, while offering a patient-friendly approach to support initial combination therapy and rapid escalation for the appropriate patients.”1

Opsynvi is indicated for use in treatment-naïve patients with PAH or those currently taking an ERA, a PDE5 inhibitor, or both.

The A DUE study evaluated the efficacy and safety of Opsynvi compared with its individual components in adults with PAH (WHO FC II or III). Investigators enrolled 197 patients with PAH who were treatment naïve or on a stable dose of an ERA or PDE5 inhibitor for at least three months.4 The primary endpoints included PVR measured at 16 weeks following therapy initiation expressed as the ratio of geometric means to baseline.4

The trial showed that the change in PVR with Opsynvi was greater than macitentan at 29% and tadalafil at 28%.5 Further, although the trial did not seek to evaluate exercise capacity, the researchers did observe a clinically significant improvement in six-minute walking distance in the cohort of patients administered Opsynvi. After adjusting for the treatment effect, the change in baseline in the Opsynvi cohort was 16.04m vs. 25.37m in the tadalafil monotherapy cohort.5

“People with PAH often live with the burden of taking many pills each day, which can pose challenges,” James F. List, MD, PhD, Global Therapeutic Area Head, Johnson & Johnson, said in a press release. “We’re thrilled to bring this single tablet combination therapy to patients, as it has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment.”1


1. U.S. FDA Approves OPSYNVI® (macitentan and tadalafil) as the First and Only Once-Daily Single-Tablet Combination Therapy for Patients with Pulmonary Arterial Hypertension (PAH). Johnson & Johnson. News release. March 22, 2024. Accessed March 25, 2024.

2. FDA approves Opsumit to treat pulmonary arterial hypertension [press release]. FDA website. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=282209 . October 18, 2013. Accessed March 25, 2024.

3. OPSUMIT (macitentan) tablets [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc; 2013. Accessed March 25, 2024.

4. Janssen submits new drug application to US FDA seeking approval of investigational single tablet combination therapy of macitentan and tadalafil for treatment of patients with pulmonary arterial hypertension. News release. Johnson & Johnson. May 30, 2023. Accessed March 25, 2024. https://www.jnj.com/janssen-submits-new-drug-application-to-u-s-fda-seeking-approval-of-investigational-single-tablet-combination-therapy-of-macitentan-and-tadalafil-for-treatment-of-patients-with-pulmonary-arterial-hypertension-pah

5. Late-breaking phase 3 A DUE data show investigational single tablet combination therapy of mecitentan and tadalafil significantly improves pulmonary hemodynamics versus monotherapy in patients with pulmonary arterial hypertension (PAH). News release. Janssen. March 6, 2023. Accessed March 25, 2024. https://www.janssen.com/us/sites/www_janssen_com_usa/files/late-breaking_phase_3_a_due_data_show_investigational_single_tablet_combination_therapy_of_macitentan_and_tadalafil_significantly_improves_pulmonary_hemodynamics_versus_monotherapy_in_patients_with_pulmonary_arterial_hypertension_pah.pdf

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