FDA approves Macitentan and Tadalafil 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 press release. The combination tablet can be used in individuals who are on treatment or those who are already on an endothelin receptor antagonist, phosphodiesterase 5 inhibitor, or both. The combination tablet can also be used in people who are being treated with stable doses of macitentan 10 mg and tadalafil 40 mg, as two 20 mg tablets, as separate tablets.1

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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 there was no single-pill combination therapy targeting 2 or more pathways, Kelly Chin, MD, professor of internal medicine and director of the Hypertension Program, said in a press release UT Southwestern Medical Center Pulmonary. liberation1

Since co-administration of macitentan and tadalafil is commonly prescribed for the initial therapy of PAH, the introduction of a single pill that combines both is promising for treating physicians as it may help to bridge the gap between clinical guidelines and daily clinical practice, while providing a patient-friendly approach to support initial combination therapy and rapid escalation for appropriate 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 greater reductions in pulmonary vascular resistance (PVR) after 16 weeks compared with either drug in monotherapy.1 The study was a multicenter, double-blind, randomized phase 3 study that enrolled people 18 years of age or older with idiopathic, hereditary, 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 study A TWO

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

ClinicalTrials.gov ID: NCT03904693

Sponsor: actelion

Completion date (estimated): September 2024

The researchers included patients from 76 sites in 16 counties from October 15, 2019, to August 23, 2022, with 187 included in the treatment randomization. According to the study authors, there were 108 individuals assigned to the combination tablet, 25 to macitentan monotherapy, and 44 to tadalafil monotherapy. Approximately 53% were in the treatment phase at treatment randomization.2

PVR was reduced in all groups from baseline to week 16, with a similar decrease among the monotherapy groups. There was a greater decrease in the combination treatment group, according to the results. The effects were also seen in treated patients. The researchers also reported that 3 people died in the combination arm, but the deaths were unrelated to treatment. In addition, adverse events (AEs) leading to treatment discontinuation, serious AEs, and AEs of special interest, including anemia, hypotension, and edema, were more frequent in the combination group. According to the study authors, the most common treatment-related AEs in the combination arm were headache in 16.8% and peripheral edema in 13.1%.2

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

  1. The US FDA approves Opsynvi (macitentan and tadalafil) as the first and only once-daily single-pill 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/us-fda-approves-opsynvi-macitentan-and-tadalafil-as-the- first-and-only-one-one-die-tablet-combination-therapy-for-patients-with-pulmonary-arterial-hypertension-pah
  2. Grnig E, Jansa P, Fan F, et al. Randomized trial of Macitentan/Tadalafil single-pill 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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