Johnson & Johnson Receives Positive CHMP Opinion for Yuvanci® (Single Tablet Combination Therapy [STCT] of Macitentan and Tadalafil) for Treatment of Patients with Pulmonary Arterial Hypertension (PAH)

If approved, Yuvanci^® would become the only single tablet combination for treatment for patients with PAH

Johnson & Johnson’s comprehensive PAH portfolio has the potential to cover all guideline-recommended treatment pathways

BEERSE, BELGIUM (26 July, 2024) – Janssen-Cilag International NV, a Johnson & Johnson company, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the Marketing Authorisation (MA) of Yuvanci^®. Yuvanci^® is a single tablet combination therapy of macitentan 10 mg and tadalafil 40 mg (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.[i]

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.[ii]^,[iii] The 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) pulmonary hypertension (PH) guidelines have strengthened recommendations on initial double combination therapy with macitentan and tadalafil for PAH patients without cardiopulmonary comorbidities.[iv] However, this requires patients to take multiple pills as no single tablet that targets two or more PAH-specific pathways is available for these patients in Europe.

“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,^4,[v]” said Tamara Werner-Kiechle, M.D., EMEA Therapeutic Area Lead Neuroscience and Cardiopulmonary, Johnson & Johnson Innovative Medicine. “Bringing a single tablet combination follows the ESC/ERS guidelines, which recommend initial double and triple combination therapy,⁴ and could represent an important new option for adults living with PAH who face complex treatment regimens.[vi]^,[vii]”

The CHMP positive opinion for M/T STCT is based on data from the Phase 3 A DUE study. The A DUE study was 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).[viii] The study was designed to compare the efficacy and safety of M/T STCT to each monotherapy, macitentan or tadalafil.⁸ 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.⁸

Treatment with M/T STCT resulted in a statistically significant effect of 0.71 (95% Confidence Interval [CI] 0.61, 0.82, p < 0.0001) representing a 29% reduction in PVR as compared to macitentan, and of 0.72 (95% CI 0.64, 0.80, p < 0.0001) representing a 28% reduction in PVR as compared to tadalafil.⁸ Consistent efficacy of M/T STCT on the primary endpoint was seen across subgroups of age, sex, race, and baseline WHO FC.^1,8 Additionally, consistent efficacy was observed in patients who were either treatment-naïve, or previously exposed to an endothelin receptor antagonist (ERA) or phosphodiesterase type 5 inhibitor (PDE5i).⁸

The most common adverse events (AEs) (occurring in the M/T STCT-treated patients) from the combined double-blind/open-label A DUE study data were anaemia/haemoglobin decrease, oedema/fluid retention, and headache. The most common serious AE was anaemia, followed by palpitations, hypotension, intermenstrual bleeding, oedema/fluid retention and influenza.¹

“Today’s positive opinion represents a significant step forward and underlines our commitment to providing solutions for patients in the PAH community,” said James F. List, M.D., Ph.D., Global Therapeutic Area Head, Cardiopulmonary, Johnson & Johnson Innovative Medicine. “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.”

Pending European Commission (EC) approval, Yuvanci^® will be the only single tablet combination therapy in Europe for PAH. Approval by the EC will also mean J&J’s PAH portfolio will have the potential to cover all guideline-recommended treatment pathways. Today’s positive CHMP opinion follows the New Drug Application (NDA) approval of OPSYNVI^® (macitentan and tadalafil) by the U.S. Food and Drug Administration (FDA) in March 2024 for the treatment of patients with PAH.[ix]

[i] Yuvanci EU Summary of Product Characteristics. July 2024. Confidential. 

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

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

[iv] 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.

[v] Chin KM, et al. Psychometric Validation of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire: Results of the SYMPHONY Trial. Chest. 2018; 154(4):848-61.

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

[vii] 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.

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

[ix] Johnson & Johnson. 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). Available at: 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. Last accessed: July 2024.