European Commission approves Yuvanci® (Single Tablet Combination Therapy [STCT] of Macitentan and Tadalafil) for Treatment of Patients with Pulmonary Arterial Hypertension (PAH)

BEERSE, BELGIUM (Monday 30 September, 2024) – Janssen-Cilag International NV, a Johnson & Johnson company, announced today that the European Commission (EC) has approved Yuvanci^® (macitentan 10 mg and tadalafil 40 mg single tablet combination therapy [M/T STCT]) as a substitution therapy for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III, who are already treated with the combination of macitentan and tadalafil given concurrently as separate tablets.^[1]

“In the Phase 3 A DUE study, the macitentan and tadalafil single tablet combination therapy demonstrated a reduction of 29 percent in pulmonary vascular resistance as compared to macitentan, and 28 percent reduction in pulmonary vascular resistance as compared to tadalafil,^[2]” said Professor Ekkehard Grunig, MD, Professor of Internal Medicine, Heidelberg University.^a “These results, along with the consistent efficacy across different patient subgroups in the study are encouraging.^1,2 This single tablet combination therapy represents an important new treatment option for many people living with PAH, who, until now, had no single tablet option available.”

PAH is a rare, progressive and life-threatening disease characterised by the constriction of small pulmonary arteries and elevated blood pressure (hypertension) in the pulmonary circulation that eventually leads to right heart failure and death.^[3],[4] Initial double combination therapy with macitentan and tadalafil for PAH patients without cardiopulmonary comorbidities has the highest class of recommendation in the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) pulmonary hypertension (PH) guidelines.^[5] However, this requires patients to take multiple pills as, until now, no single tablet that targets two or more PAH-specific pathways has been available for these patients in Europe.

“People living with PAH face complex treatment regimens, with many having to take multiple pills per day.^[6],[7] This can deeply impact their daily lives as they might struggle to maintain adherence to their treatment regimen,^6,7” said Tamara Werner-Kiechle, M.D., EMEA Therapeutic Area Lead Neuroscience and Cardiopulmonary, Johnson & Johnson Innovative Medicine. “This approval addresses a significant unmet need for the PAH community and we are delighted to bring a new and innovative treatment option to adults living with PAH that follows the ESC/ERS guidelines, which recommend initial double and timely escalation to triple combination therapy.⁵”

The EC approval is based on results from the Phase 3 A DUE study, a multi-national, multi-centre, double-blind, adaptive, randomised, active-controlled, parallel-group study in 187 adult patients with PAH (WHO FC II to III).² The study was designed to compare the efficacy and safety of M/T STCT to each monotherapy (macitentan or tadalafil).² The study met its primary endpoint, demonstrating change in pulmonary vascular resistance (PVR) expressed as the ratio of Week 16 to baseline in patients with PAH, for the comparison of M/T STCT versus the individual monotherapies.²

The most common adverse events (AEs) occurring in M/T STCT-treated patients from the combined double-blind / open-label A DUE study data were anaemia/haemoglobin decrease (22.2%), oedema/fluid retention (17.3%), and headache (14.1%). In the study, the most common serious adverse event (SAE) was anaemia (1.1%, n=2), followed by palpitations, hypotension, intermenstrual bleeding, oedema/fluid retention and influenza, each reported in 1 patient (0.5%).¹

“Today’s approval represents an important milestone in our ambition to transform PAH into a manageable condition so that people can lead a full life,” said JoAnne Foody, M.D., Global Therapeutic Area Head, Cardiopulmonary, Johnson & Johnson Innovative Medicine. “We are now in a position to provide treatment options with three different mechanisms of action in our comprehensive PAH portfolio, which now covers all three guideline-recommended foundational treatment pathways. We are proud to lead the way in our commitment to bringing a variety of healthcare solutions for people living with this devastating condition.”

[1] Yuvanci EU Summary of Product Characteristics. September 2024. Confidential.

[2] Grünig E, et al. Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. JACC. 2024; 83(4):473–484.

[3] Vachiéry JL, Gaine S. Challenges in the diagnosis and treatment of pulmonary arterial hypertension. Eur Respir Rev. 2012; 21:313-20.

[4] Hoeper MM, Gibbs JS. The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur Respir Rev. 2014;23:450-457.

[5] 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022; 43:3618–3731. https://doi.org/10.1093/eurheartj/ehac237.

[6] Grady D, et al. Medication and patient factors associated with adherence to pulmonary hypertension targeted therapies. Pulm Circ. 2018; 8:1–9.

[7] Lauffenburger JC, et al. Effect of combination therapy of adherence among US patients initiating therapy for hypertension: a cohort study. J Gen Intern Med 2017; 32(6):619–25.