FDA Approves Macitentan, Tadalafil Combination Tablet for PAH

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 company release. The combination tablet can be used in people who are not on medication or who are already on an endothelin receptor antagonist, a phosphodiesterase 5 inhibitor, or both. The combination tablet can also be used in people treated with stable doses of macicentan 10 mg and tadalafil 40 mg, as two 20 mg tablets, as separate tables.1

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Clinical guidelines recommend treating patients with initial and subsequent 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 that targets 2 or more pathways is available, Kelly Chin, MD, professor of Internal Medicine and director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, he said to the press. release.1

Since the administration of macitentan and tadalafil together is usually given as the initial treatment of PAH, the introduction of a single tablet that combines the two is promising for clinicians as it can help close the gap between clinical guidelines and daily clinical practice, while providing a patient-friendly way to support the combined initial and and the rapid increase in eligible patients, Chin said.1

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

About A DUE Study

Trial name: A Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies with Concomitant Fixed-dose Combination Therapy in Subjects with Pulmonary Arterial Hypertension (PAH)

ClinicalTrials.gov ID: NCT03904693

Sponsor: Actellion

Completion Date (Estimated): September 2024

The investigators included patients from 76 sites in 16 states from October 15, 2019, to August 23, 2022, and 187 were included in the randomized treatment. There were 108 people who were given the combination tablet, 25 in macicentan monotherapy, and 44 in tadalafil monotherapy, according to the study authors. About 53% were naïve to randomized treatment.2

PVR was reduced in all groups from baseline to week 16, with similar reductions between the monotherapy groups. There was a significant decrease in the combined treatment group, according to the results. The results were also observed in patients treated with medications. Investigators also reported that 3 people died of an arm injury, but the deaths were not related to the treatment. In addition, adverse events (AEs) leading to discontinuation, serious AEs, and AEs of special interest, including anemia hypotension, and edema, were more common in the combination group. The most treatment-related AEs in the combined arm were headache in 16.8% and peripheral edema in 13.1%, according to the study authors.2

According to the press release, this combination has a boxed warning for the risk of embryo-fetal toxicity and requires female patients to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy.1

  1. US FDA Approves Opsynvi (macitentan and tadalafil) as First-Time and Once-A-Day Tablet Combination Therapy in 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/us-fda-approves-opsynvi-macitentan-and-tadalafil-as-the-first-and -only-once-a-day-one-tablet-combination-treatment-of-patients-with-pulmonary-arterial-hypertension-pah
  2. Grnig E, Jansa P, Fan F, et al. A 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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