J&J secures EC approval for first single-pill PAH combo

The European Commission (EC) has given the green light to Johnson and Johnson’s Yuvanci (a combination of macitentan and tadalafil) for the treatment of pulmonary arterial hypertension (PAH). This newly approved medication stands out as the first single-pill treatment option available to European patients suffering from PAH.

Pulmonary arterial hypertension is a rare and progressive condition characterized by high blood pressure in the pulmonary arteries without an identifiable cause. Existing treatments typically involve dual combination therapy with macitentan and tadalafil, often administered in multiple pills. This multi-pill regimen can significantly affect patients' lives, as maintaining adherence to such a treatment schedule can be challenging. Dr. Tamara Werner-Kiechle, the therapeutic area lead for neuroscience and cardiopulmonary drugs at Johnson & Johnson Innovative Medicine, highlighted the daily struggles PAH patients face in adhering to complex treatment regimens.

Yuvanci has been developed as a substitution therapy for long-term treatment in adults classified under the World Health Organization’s (WHO) Functional Class (FC) II to III. This classification includes patients experiencing slight physical activity limitations who are still comfortable at rest, as well as those with marked limitations in physical activity. To be eligible for Yuvanci, patients must have already been treated with a two-pill combination of macitentan and tadalafil. Johnson and Johnson markets macitentan as Opsumit, while Eli Lilly sells tadalafil under the brand name Cialis for PAH.

The EC’s approval of Yuvanci is based on data from the Phase III A DUE study (NCT03904693). This study also prompted a positive recommendation from the European Medicines Agency’s (EMA) Committee for Human Medicinal Products in July. The Phase III A DUE clinical study results were presented at the American College of Cardiology’s 72nd Annual Scientific Session. In this double-blind study, patients treated with Yuvanci showed significant improvements in pulmonary vascular resistance (PVR) and pulmonary hemodynamics. Specifically, patients on the combination therapy demonstrated a 44% reduction in PVR, in contrast to a 22% reduction in the group receiving Adcirca monotherapy.

The individual components of Yuvanci work through different mechanisms. Opsumit, an endothelin receptor antagonist, treats PAH by inhibiting pathways linked to vasoconstriction, fibrosis, and proliferation. On the other hand, Cialis, a phosphodiesterase type-5 inhibitor, treats the disorder by increasing cyclic guanosine monophosphate (cGMP), which leads to the relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.

Johnson and Johnson has also submitted a new drug application to the US Food and Drug Administration (FDA) for Yuvanci in May 2023. The application received approval for submission in March 2024.