Single Tablet Macitentan, Tadalafil Combination for Pulmonary Arterial Hypertension May Improve Patient Quality of Life

Janssen Pharmaceutical Companies has submitted a new drug application to the FDA for the approval of an investigational combination therapy of macitentan 10 mg and tadalafil 40 mg in a single tablet for the long-term treatment of pulmonary arterial hypertension (PAH) in adults with WHO functional class.¹

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The application includes positive data from the phase 3 A DUE (NCT03904693) study, which met its primary endpoint and demonstrated that the investigational tablet improved pulmonary hemodynamics compared to the same drugs as monotherapies in this patient population.¹

“[Patients] with PAH are often prescribed numerous medicines to manage their condition, so the potential to offer a single tablet combination of 2 guideline-recommended therapies could not only decrease pill burden but may also help improve the patient treatment experience and clinical outcomes," James F. List, MD, PhD, global therapeutic area head at Janssen Research & Development, LLC, said in a statement. “[The] submission builds on our decades-long commitment to address patient needs and bring forward medicines with the potential to offer an improved standard of PAH care."¹

A DUE is a double-blinded, randomized study designed to compare the efficacy and safety of the single tablet compared to the monotherapies of the individual drugs for those with PAH.¹

Investigators included 197 individuals with PAH from across 148 sites in 199 countries in WHO functional class II or III who were treatment naïve or on a stable dose of an endothelin receptor antagonist or a phosphodiesterase type 5 inhibitor for at least 3 months.¹

The primary endpoints included pulmonary vascular resistance (PVR), which was measured at 16 weeks after initiation of treatment and expressed as the ratio of geometric means to baseline.¹ The PVR change with the single tablet was greater than macitentan at 29% and tadalafil at 28%.²

The safety profile of the single tablet therapy was consistent with the safety profile of the individual drugs, mecitentan and tadalafil. Currently, the open label arm of the A DUE study is still ongoing.¹

Though the study was not designed to demonstrate a benefit on exercise capacity, investigators did find there was a clinically relevant improvement in 6-minute walking distance in favor of the single tablet compared to the monotherapies. When the treatment effect was adjusted, the change in baseline in the single tablet group compared to the mecitentan group was 16.04m and 25.37m compared to that tadalafil group.²

The latest guideline recommendations from the European Society of Cardiology/European Respiratory Society included initiating a double combination of the drugs for individuals with PAH without cardiopulmonary comorbidities. This requires the individual to take multiple pills because no single tablet has been approved for these patients.¹

Mecitentan and tadalafil single tablet is the first investigational combination therapy that combined both of these drugs in a single tablet for once daily administration.¹

References

1. Janssen submits new drug application to US FDA seeking approval of investigational single tablet combination therapy of macitentan and tadalafil for treatment of patients with pulmonary arterial hypertension. News release. Johnson & Johnson. May 30, 2023. Accessed June 2, 2023. https://www.jnj.com/janssen-submits-new-drug-application-to-u-s-fda-seeking-approval-of-investigational-single-tablet-combination-therapy-of-macitentan-and-tadalafil-for-treatment-of-patients-with-pulmonary-arterial-hypertension-pah
2. Late-breaking phase 3 A DUE data show investigational single tablet combination therapy of mecitentan and tadalafil significantly improves pulmonary hemodynamics versus monotherapy in patients with pulmonary arterial hypertension (PAH). News release. Janssen. March 6, 2023. Accessed June 2, 2023. https://www.janssen.com/us/sites/www_janssen_com_usa/files/late-breaking_phase_3_a_due_data_show_investigational_single_tablet_combination_therapy_of_macitentan_and_tadalafil_significantly_improves_pulmonary_hemodynamics_versus_monotherapy_in_patients_with_pulmonary_arterial_hypertension_pah.pdf