CLINICAL DATA

OPSYNVI is a single-tablet combination containing 2 oral components used to treat pulmonary arterial hypertension (PAH): macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase-5 inhibitor (PDE-5i).¹ The authors of 2 bioequivalence studies provide the following explanation for why OPSYNVI tablets are formulated with tadalafil as the PDE-5i component instead of sildenafil.²

The approval to use macitentan as monotherapy and as part of a combination therapy with PDE-5i was based on the data generated in the long-term, event-driven SERAPHIN study that had approximately 61% of patients receiving a PDE-5i, mainly sildenafil, as background therapy at baseline. Even though sildenafil was the most frequently used PDE-5i in SERAPHIN, it needs to be taken 3 times daily, whereas macitentan needs to be taken only once daily. Therefore, the once daily administered tadalafil, with the same mode of action as sildenafil and indicated for the treatment of PAH, was selected for use in a fixed-dose combination (FDC) with macitentan. As sildenafil and tadalafil possess similar efficacy and safety profiles, the add-on benefit of macitentan to tadalafil was expected to be similar to that observed for sildenafil in the SERAPHIN study.²

OPTIMA was a multicenter, prospective, single-arm, open-label phase 4 study that evaluated the efficacy, safety, and tolerability of initial combination therapy with macitentan and tadalafil in newly diagnosed patients with PAH.³ TRITON was a multicenter, double-blind, placebo-controlled phase 3b study with newly diagnosed treatment-naïve PAH patients randomized 1:1 to initial triple (macitentan, tadalafil, and selexipag) or double combination therapies (macitentan, tadalafil, and placebo).⁴ REPAIR was a prospective, multicenter, single-arm, open-label phase 4 study that evaluated the effect of macitentan 10 mg on right ventricular remodeling and hemodynamic outcomes. Macitentan 10 mg was initiated as an initial combination therapy with a PDE-5i in 38% (n=27) of treatment-naïve patients.⁵ Based on the data from OPTIMA and TRITON, for patients with idiopathic, heritable, or drug-associated PAH or PAH associated with connective tissue disorder (PAH-CTD) who do not have cardiopulmonary comorbidities, the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines elevated the recommendation of an initial oral double combination therapy of macitentan and tadalafil to Class I (Level of evidence B). Only initial oral double combination therapies of macitentan plus tadalafil and ambrisentan plus tadalafil are "recommended" at the highest Class I, whereas initial oral double combination therapies of macitentan plus sildenafil, ambrisentan plus sildenafil, bosentan plus sildenafil, and bosentan plus tadalafil are relegated to Class IIa recommendation which "should be considered.”⁶

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 28 January 2025.