FDA Approves Macitentan, Tadalafil Combination Tablet for Pulmonary Arterial Hypertension

The FDA has approved a single-tablet combination of macitentan and tadalafil (Opsynvi; Johnson & Johnson) for the chronic treatment of pulmonary arterial hypertension (PAH) in adults who are treatment-naïve or are already on an endothelin receptor antagonist, phosphodiesterase 5 inhibitor, or both, according to a press release from Johnson & Johnson.¹

The combination is indicated for patients with PAH categorized as WHO Group I and WHO functional class II-III, and the tablet can be used in those being treated with stable doses of macitentan 10 mg and tadalafil 40 mg (taken as two 20 mg tablets), as separate tablets.

FDA approved | Image credit: wladimir1804 - stock.adobe.com

The approval was based on data from the phase 3, double-blind, randomized A DUE study (NCT03904693), in which the single-pill macitentan and tadalafil combination outperformed either drug as a monotherapy.² From baseline to 16 weeks, patients with PAH treated with the single-pill combination showed greater reductions in pulmonary vascular resistance (PVR) vs those treated with macitentan or tadalafil monotherapy.

“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 no single-tablet combination therapy targeting two or more pathways was available,” Kelly Chin, MD, A DUE investigator and professor of Internal Medicine and director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, said in a statement.¹ “As administration of macitentan and tadalafil together are commonly prescribed for initial therapy for PAH, the introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice, while offering a patient-friendly approach to support initial combination therapy and rapid escalation for the appropriate patients.”

In the A DUE study, a total of 187 patients were randomized to receive either single-tablet macitentan and tadalafil (n = 108), mecitentan monotherapy (n = 35), or tadalafil monotherapy (n = 44). While the monotherapy groups saw similar reductions in PVR, those in the single-tablet macitentan and tadalafil group saw significantly greater reductions.² Compared with the macitentan and tadalafil groups, the combination group experienced a 29% greater reduction (geometric mean ratio, 0.71; 95% confidence level [CL], 0.61-0.82; P < .0001) and 28% greater reduction (geometric mean ratio, 0.72; 95% CL, 0.64-0.80; P < .0001) in PVR, respectively. At randomization, 53% of patients were treatment-naïve.

There were more frequent adverse events leading to discontinuation in the combination therapy group, and the single-tablet macitentan and tadalafil formulation has a Boxed Warning due to the risk of embryo-fetal toxicity.^1,2 Female patients are required to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy program.

“People with PAH often live with the burden of taking many pills each day, which can pose challenges,” James F. List, MD, PhD, Global Therapeutic Area Head, Johnson & Johnson, said.² “We’re thrilled to bring this single tablet combination therapy to patients, as it has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment.”

References

1. US FDA approves Opsynvi (macitentan and tadalafil) as the first and only once-daily single-tablet 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/u-s-fda-approves-opsynvi-macitentan-and-tadalafil-as-the-first-and-only-once-daily-single-tablet-combination-therapy-for-patients-with-pulmonary-arterial-hypertension-pah

2. Grünig E, Jansa P, Fan F, et al. Randomized trial of macitentan/tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83(4):473-484. doi:10.1016/j.jacc.2023.10.045