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, July 26, 2024 (GLOBE NEWSWIRE) —  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.¹

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.^2,3 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.⁴ 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,” ^4,5 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.” ^6,7

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).⁸ 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.⁹

About Pulmonary Arterial Hypertension (PAH)

PAH is a specific, rare form of pulmonary hypertension (PH) with approximately 48-55 cases per million adults, and there is currently no cure.^2,4 PAH is a serious, progressive disease with a variety of aetiologies and has a major impact on patients’ functioning as well as their physical, psychological and social wellbeing.^3,5

PAH evolves silently over years, as symptoms such as breathlessness, dizziness and fatigue are non-specific and can be confused with more common conditions like asthma and chronic obstructive pulmonary disease (COPD).² On average it takes two years from the onset of symptoms for PAH to be diagnosed, and in some instances up to four years.^2,10 This means that by the time a patient is diagnosed, their PAH is typically in an advanced stage with severe symptoms and a poor prognosis.² The last decade has seen significant advances in the understanding of the pathophysiology of PAH, transforming the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago, to delayed disease progression today.² However, PAH patients are facing a greater pill burden due to complex treatment regimens involving multiple pills.^6,7 The PAH patient population is also ageing, leading to an increasing number of concomitant medications to treat comorbidities.⁴

About macitentan/tadalafil STCT

Macitentan 10 mg and tadalafil 40 mg STCT is a therapy that combines the ERA, macitentan, and the PDE5i, tadalafil.¹ Macitentan works by dilating the narrow blood vessels between the right heart and the lungs, making it easier for the heart to pump blood through them, as well as reducing and preventing the overgrowth of cells in the walls of these vessels.¹¹ Tadalafil helps to relax the blood vessels in the lungs, widening them to decrease the pulmonary blood pressure to the heart and improve its function.¹²

About the A DUE study

The A DUE study was a multi-national, multi-centre, double-blind, adaptive, randomised, active-controlled, parallel-group study in 187 patients with PAH (WHO FC II–III).⁸ The study was designed to compare the efficacy and safety of Yuvanci^® single tablet combination therapy of macitentan 10 mg and tadalafil 40 mg (M/T STCT) to each monotherapy, macitentan or tadalafil.⁸ Patients with pulmonary vascular resistance (PVR) of at least 240 dyn×s/cm5 were randomised to receive M/T STCT (n=108), 10 mg macitentan monotherapy (n=35) or 40 mg tadalafil monotherapy (n=44), once daily. Patients who were not on a therapeutic PDE-5i dose at baseline, received a 1-week titration period of macitentan 10 mg and tadalafil 20 mg. Patients who received treatment during the double-blind treatment period (n=186) were either treatment-naïve (52.7%) to any PAH specific monotherapy, or on an ERA (17.2%), or a PDE5i (30.1%). Patients enrolled had idiopathic PAH (50.5%), heritable PAH (4.8%), PAH associated with connective tissue disease (34.9%), or PAH associated with congenital heart disease (3.2%). The mean age was 50.2 years (range 18–80), 20.4% of patients were ≥ 65 years of age, 22% were male and 61.8% were white. At the time of enrollment, 51.1% of patients were WHO FC II and 48.9% were WHO FC III.¹ The primary endpoint of the study was change in 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.¹ The key secondary endpoint was change in mean 6-minute walk distance (6MWD) from baseline to 16 weeks of therapy in patients with PAH, for the comparison of M/T STCT versus the individual monotherapies.¹

About Johnson & Johnson 

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Learn more at www.janssen.com/emea. Follow us at https://www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen-Cilag International NV, Janssen-Cilag GmbH and Janssen Research & Development, LLC are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements 

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of Yuvanci. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, Janssen-Cilag GmbH and Janssen Research & Development, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen-Cilag International NV, Janssen-Cilag GmbH, Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References

¹ Yuvanci EU Summary of Product Characteristics. July 2024. Confidential. 

² Vachiéry JL, Gaine S. Challenges in the diagnosis and treatment of pulmonary arterial hypertension. Eur Respir Rev. 2012; 21:313-20.

³ Hoeper MM, Gibbs JS. The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur Respir Rev. 2014;23:450-457.

⁴ 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.

⁵ 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.

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.

⁸ Grünig E, et al. Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. JACC. 2024; 83(4):473–484.

⁹ 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.

¹⁰ Armstrong I, Billings C, Kiely DG, et al. The patient experience of pulmonary hypertension: a large cross sectional study of UK patients. BMC Pulm Med. 2019;19:67.

¹¹ Opsumit Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/opsumit-epar-product-information_en.pdf Last accessed July 2024.

¹² Adcirca Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/adcirca-epar-product-information_en.pdf Last accessed July 2024.

CP-464755
DOP-July 2024

CONTACT: Media contact:
Sarah Smith
ssmith49@its.jnj.com
+44 7920 082 012

Investor contact:
Raychel Kruper
investor-relations@its.jnj.com