FDA Approves Macitentan, Tadalafil Combination Tablet for PAH


The combination tablet (Opsynvi; Johnson & Johnson) can also be used for individuals with pulmonary arterial hypertension who are being treated with stable doses of macitentan and tadalafil as separate tables.

The FDA has approved macitentan and tadalafil (Opsynvi; Johnson & Johnson) as a single tablet combination, for the chronic treatment of pulmonary arterial hypertension (PAH) in adults, according to a press release from the company. The combination tablet can be used in individuals who are treatment-naïve or those that are already on an endothelin receptor antagonist, phosphodiesterase 5 inhibitor, or both. The combination tablet can also be used in individuals who are being treated with stable doses of macitentan 10 mg and tadalafil 40 mg, as two 20 mg tablets, as separate tables.1

3d rendered illustration of heart attack and heart disease 3D illustration | Image Credit: santoelia - stock.adobe.com

Image Credit: santoelia - stock.adobe.com

“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 2 or more pathways was available,” Kelly Chin, MD, professor of Internal Medicine and director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, said in a press release.1

“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,” Chin said.1

The approval is based on data from the A DUE (NCT03904693) phase 3 study, showing that the single-pill combination had greater reductions in pulmonary vascular resistance (PVR) after 16 weeks compared to either drug in monotherapy.1 The study was a multicenter, double-blind, randomized phase 3 study that included individuals aged 18 years and older with idiopathic, heritable, drug- or toxin-induced PAH, or diagnosed PAH that was associated with connective tissue disease, HIV, portal hypertension, or corrected congenital heart disease, according to the study authors.2

About The A DUE Study

Trial Name: Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

ClinicalTrials.gov ID: NCT03904693

Sponsor: Actelion

Completion Date (Estimated): September 2024

Investigators included patients from 76 sites in 16 counties from October 15, 2019, to August 23, 2022, with 187 being included in the treatment randomization. There were 108 individuals assigned to the combination tablet, 25 to the macitentan monotherapy, and 44 to the tadalafil monotherapy, according to the study authors. Approximately 53% were treatment-naïve at treatment randomization.2

PVR was reduced in all groups from baseline to week 16, with a similar decrease between the monotherapy groups. There was a greater decrease in the combination treatment group, according to the results. The effects were also seen for treatment-naïve patients. Investigators also reported that 3 individuals died in the combination arm, but the deaths were not related to treatment. Further, adverse events (AEs) leading to discontinuation, serious, AEs, and AEs of special interest, including anemia hypotension, and edema, were more frequent in the combination group. The most common treatment-related AEs in the combination arm were headache at 16.8% and peripheral edema at 13.1%, according to the study authors.2

According to the press release, the combination had a boxed warning due to the risk of embryo-fetal toxicity and requires patients who are female to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy program.1

  1. US FDA Approves Opsynvi (macitentan and tadalafil) as the First and Only Once-Daily Single-Tablet Combination Therapy for Patients with Pulmonary Arterial Hypertension (PAH). News release. Johnson & Johnson. March 22, 2024. Accessed March 25, 2024. https://www.jnj.com/media-center/press-releases/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
  2. Grünig E, Jansa P, Fan F, et al. Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. J Am Coll Cardiol. 2024;83(4):473-484. doi:10.1016/j.jacc.2023.10.045
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