Janssen's Opsumit in Combination with Tadalafil Achieves 47% Reduction in PVR in Phase IV OPTIMA Trial for Newly Diagnosed PAH Patients

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Johnson & Johnson’s Janssen Pharmaceuticals subsidiary, Actelion, recently announced data from the OPTIMA study. This was a prospective, multicenter, single-arm, open-label, Phase IV trial evaluating the efficacy, safety, and tolerability of Opsumit (macitentan) in combination with the PDE5 inhibitor tadalafil as an initial oral treatment regimen for patients with newly diagnosed pulmonary arterial hypertension (PAH). A total of 46 PAH patients (WHO Group 1) were enrolled and treated in the study, and all patients were included in the efficacy and safety analyses.

The results showed that at Week 16 of treatment, the primary endpoint of mean pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) decreased by 47% from baseline (geometric mean ratio of Week 16 to baseline: 0.53; 95% CI: 0.47, 0.59). Furthermore, the results demonstrated improvements in hemodynamics, functional parameters (including 6-minute walk distance), and risk status.

The safety and tolerability results were consistent with those from previous clinical trials supporting the approval and use of Opsumit 10 mg once daily. The most common adverse events in the study were peripheral edema (28.3%), headache (23.9%), diarrhea (19.6%), dyspnea (15.2%), anemia (13.0%), and fatigue (13.0%). Four patients had hemoglobin levels decrease to below 10 g/dL, and one patient had transaminase levels ≥3 times the upper limit of normal. Three patients discontinued treatment due to adverse events, and three patients died during the study. Causes of death included cardiac arrest, heart failure, and multi-organ failure with sepsis.

Pulmonary arterial hypertension (PAH) is a specific type of pulmonary hypertension characterized by thickening and stiffening of the pulmonary artery walls (the vessels carrying blood from the right side of the heart to the lungs), which narrows the lumen for blood flow and elevates blood pressure. Despite recent advances, PAH remains a severe, progressive disease with no cure, and one-third of patients die within five years of diagnosis. Risk stratification in PAH is a crucial tool for monitoring disease progression and treatment response, with the primary therapeutic goal being to achieve and maintain a low-risk status.

The data from the OPTIMA study are highly significant, as improvement in pulmonary vascular resistance (PVR) is an important indicator of right ventricular function and a key therapeutic goal in the treatment of patients with pulmonary arterial hypertension (PAH). Current clinical guidelines for PAH recommend initial dual oral combination therapy.

The results of the OPTIMA study confirmed the efficacy and safety of initial oral dual therapy with Opsumit and tadalafil in patients with pulmonary arterial hypertension (PAH), and supplemented the evidence supporting combination therapy as standard of care.

Opsumit is a product acquired by Johnson & Johnson following its $30 billion cash acquisition of Actelion in 2017. The active pharmaceutical ingredient of this drug is macitentan, a dual endothelin receptor antagonist that relaxes pulmonary arteries and lowers blood pressure. In the United States and the European Union, Opsumit has been approved for the treatment of pulmonary arterial hypertension (PAH).

Opsumit Can Improve Patients' Exercise Capacity: Clinical Study Data in WHO Functional Class II-III PAH Patients Showed That, Based on the 6-Minute Walk Distance Assessment, Patients Treated with Opsumit Had a Mean Increase of 22 Meters in Walking Distance at Month 6 Compared to Those Not Taking Opsumit.

It is important to note that Opsumit, like other drugs in its class, carries a black box warning indicating embryonic/fetal toxicity.

Tadalafil is a PDE5 selective inhibitor developed by Eli Lilly and Company. It was first launched in the European Union in 2003 for the treatment of erectile dysfunction. In 2009, tadalafil received approval from the U.S. FDA for the treatment of pulmonary arterial hypertension (PAH).

Reference source: NewOPSUMIT^®(macitentan) Data Show Initial Combination Therapy with Tadalafil Improved Hemodynamic Clinical and Functional Parameters in Patients with Pulmonary Arterial Hypertension