J&J’s PAH Combination Tablet Moves Closer Toward Approval in Europe

Johnson & Johnson’s combination pulmonary arterial hypertension (PAH) tablet is one step closer to market authorization in the European Union (EU).

The company announced late last month that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the single-tablet combination of macitentan and tadalafil (Yuvanci) for approval for certain adult patients with PAH. The potential approval would apply to patients with World Health Organization (WHO) Functional Class II to III PAH who are already taking macitentan and tadalafil as separate tablets.

The tablet includes a 10 mg dose of macitentan and a 40 mg dose of tadalafil. In a phase 3 trial of patients with class II-III PAH published in January, the combination tablet led to superior reductions in pulmonary vascular resistance compared to either of the two drugs as monotherapy, while maintaining a safety profile similar to that of the two therapies alone.

Johnson & Johnson noted in a press release that the 2022 pulmonary hypertension guidelines from the European Society of Cardiology (ESC) and European Respiratory Society (ERS) call for combination therapy with the endothelin receptor antagonist (ERA) macitentan and the phosphodiesterase 5 (PDE-5) inhibitor tadalafil in patients with no cardiopulmonary comorbidities.

Tamara Werner-Kiechle, MD, Johnson & Johnson’s regional lead for neuroscience and cardiopulmonary diseases, said the combination tablet aligns with the ESC/ERS guidelines while also limiting the burden on patients.

“PAH is a devastating disease affecting people of all ages and the burden the condition places on the daily lives of people living with it should not be underestimated,” she said, in the press release.

The combination is sold under the brand name Opsynvi in the United States. The Food and Drug Administration approved the therapy in March for patients with WHO Group I PAH and Functional Class II to III who are treatment-naive or who are already taking an ERA, PDE5 inhibitor, or both.

The therapy is the latest in a wave of fixed-dose combination therapies built in part on the premise that fewer pills will translate to greater adherence. A 2020 systematic review of studies examining “polypill” adherence showed combination pills outperformed multiple-pill regimens in terms of adherence in 84% of studies. A review published earlier this year argued that the simplification offered by fixed-dose combination therapies is significant, though the authors also noted that there are inherent limitations, including the inability to adjust doses of the individual medications included in the tablet. In addition, combination tablets can complicate the process of identifying the causes of adverse events, though the authors said that problem is not unique to combination pills.

In the case of Yuvanci, the positive recommendation by the CHMP is a crucial step in Johnson & Johnson’s efforts to gain market authorization in Europe. The committee is responsible for the scientific review of all human therapies, after which the European Commission will review the application and make a final decision. The commission’s decision will then be binding throughout the EU.

The Yuvanci recommendation was the CHMP’s second positive recommendation for a PAH therapy in July. The committee had previously given the go-ahead to Merck’s application for the marketing of sotatercept (Winrevair) in Europe.

“We continue our commitment to transform PAH into a manageable condition and we look forward to working with health authorities to bring our single tablet combination therapy to adult patients in need across the region as soon as possible,” said James F. List, MD, PhD, the company’s global head of the cardiopulmonary therapeutic area, in the press release.