Opsynvi (macitentan/tadalafil) / J&J - LARVOL DELTA

A Budget Impact Analysis of Introducing OPSYNVI for the Treatment of Adult Patients Diagnosed With Pulmonary Arterial Hypertension (ISPOR 2025) - "Comparators included macitentan, ambrisentan, bosentan, tadalafil, sildenafil, and an ERA + PDE5i loose dose combination. Introducing OPSYNVI results in a minimal budget impact for both commercial and Medicare advantage plans. Despite its higher monthly costs, our model demonstrates that OPSYNVI could reduce hospitalization days, readmissions, and patients' progression to prostanoid. Given that PAH is a rare, progressive, fatal disease, adding OPSYNVI to a plan's formulary has negligible costs while potentially improving outcomes."

Clinical • HEOR • Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Feb 2028 ➔ Sep 2029

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Single-Tablet Combination Therapy of Macitentan/Tadalafil for Patients with Pulmonary Arterial Hypertension: Qualitative Interview Study of the A DUE Phase 3 Trial. (PubMed, Adv Ther) - "In this qualitative analysis, all 26 patients and 18 clinicians provided positive feedback on M/T FDC treatment, which was consistent across countries. Reducing the number of pills needed to treat PAH, through use of single-tablet M/T FDC, is highly valued by patients and endorsed by clinicians, who both felt the single-tablet combination therapy could have a positive effect on patients' well-being and increase treatment adherence."

Interview • Journal • P3 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=230 | Recruiting | Sponsor: Actelion | Trial completion date: May 2027 ➔ Feb 2028

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A DUE: Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=187 | Completed | Sponsor: Actelion | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • PVR

Efficacy of macitentan/tadalafil single-tablet combination therapy vs pooled monotherapy in pulmonary arterial hypertension (PAH): A DUE post hoc analysis (ERS 2024) - P3 | "Changes from baseline to Week 16 in PVR, 6-minute walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analysed. Consistent with the primary analysis, in this post hoc analysis of treatment-naïve and prior monotherapy patients, single-tablet macitentan/tadalafil fixed-dose combination improved PVR, 6MWD and NT-proBNP to a greater extent than pooled monotherapy (Table), supporting the effectiveness of a combination therapy approach over monotherapy in PAH."

Clinical • Combination therapy • Monotherapy • Retrospective data • Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=230 | Recruiting | Sponsor: Actelion | Trial completion date: Jan 2027 ➔ May 2027

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

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) (GlobeNewswire) - "Janssen-Cilag International NV...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....The CHMP positive opinion for M/T STCT is based on data from the Phase 3 A DUE study."

CHMP • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease

Effect on Exercise Capacity and Long-Term Safety and Tolerability of Macitentan and Tadalafil as a Single-tablet Combination in Patients With Pulmonary Arterial Hypertension From the A DUE Open-label Interim Analysis (ATS 2024) - P3 | "Adult PAH patients randomized to M/T FDC, macitentan or tadalafil monotherapy during the DB were transitioned to the OL, receiving M/T FDC after a 2-week titration. In the A DUE open-label interim analysis, single tablet combination therapy with macitentan and tadalafil led to further improvement in 6MWD at 6 and 12 months. Long-term safety/tolerability of MT/FDC in the open label period was comparable with that seen in the A DUE double-blind period; no new or unexpected safety concerns were revealed."

Clinical • Anemia • Cardiovascular • Hematological Disorders • Hepatology • Hypertension • Hypotension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bioequivalence and the food effect of macitentan/tadalafil 10/20 fixed-dose combination tablets versus the use of single-component tablets in healthy subjects. (PubMed, Pharmacol Res Perspect) - "This study demonstrated bioequivalence between the FDC of macitentan/tadalafil (10/20 mg) in a single tablet and the free combination of both drugs in healthy participants, and that the FDC can be taken without regard to food, similarly to the individual components. The FDC was generally safe and well tolerated."

Clinical • Journal • P1 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Sotatercept (Winrevair) for pulmonary arterial hypertension. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

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) (PRNewswire) - "Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has approved OPSYNVI...for the chronic treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group I) and WHO functional class (FC) II-III. OPSYNVI may be used in patients with PAH who are treatment-naïve or who are already on an ERA, PDE5 inhibitor or both. OPSYNVI may be used in patients who are currently treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg (20 mg x 2) as separate tablets....The FDA's approval of OPSYNVI is based on the results from the pivotal Phase 3 A DUE study..."

NDA • Pulmonary Arterial Hypertension

Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. (PubMed, J Am Coll Cardiol) - P3 | "Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693)."

Combination therapy • Journal • Cardiovascular • Hematological Disorders • Hypertension • Hypotension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Macitentan tadalafil fixed dose combination (FDC) in patients with pulmonary arterial hypertension (PAH): A subgroup analysis from A DUE (ERS 2023) - P3 | "In the A DUE study, M/T FDC consistently led to a greater improvement in PVR vs both macitentan and tadalafil monotherapies within prespecified subgroups. The treatment effect across subgroups was comparable to that in the overall population.; Physiology; Respiratory intensive care; Epidemiology; General respiratory patient care; Public health; Pulmonary function testing"

Clinical • Cardiovascular • Critical care • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Macitentan tadalafil Fixed Dose Combination (FDC) in treatment-naive and prior monotherapy patients with Pulmonary Arterial Hypertension (PAH): insights from A DUE (ESC 2023) - "In A DUE, the effect of M/T FDC vs both monotherapies on PVR and 6MWD in treatment-naïve and prior ERA/PDE5i patients was consistent with that observed in the overall population."

Clinical • Monotherapy • Cardiovascular • Hypertension

Janssen Submits Marketing Authorisation Application to the European Medicines Agency (EMA) Seeking Approval of Single Tablet Combination Therapy (STCT) of Macitentan and Tadalafil for Treatment of Patients with Pulmonary Arterial Hypertension (PAH) (GlobeNewswire) - "The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking approval of a single tablet combination therapy of macitentan 10 mg and tadalafil 40 mg (M/T STCT) for the long-term treatment of pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) in adult patients of WHO functional class (FC) II-III. The application is based on data from the Phase 3 A DUE study, which demonstrated that the M/T STCT significantly improved pulmonary haemodynamics (blood flow through pulmonary blood vessels) versus macitentan and tadalafil monotherapies in patients with PAH."

European regulatory • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease

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) (PRNewswire) - "The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of an investigational single tablet combination therapy of macitentan 10mg and tadalafil 40mg (M/T STCT) for the long-term treatment of pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) in adult patients with WHO functional class (FC) II-III.1 The application is based on positive data from the Phase 3 A DUE study, which met its primary endpoint and demonstrated that M/T STCT significantly improved pulmonary hemodynamics (blood flow through pulmonary blood vessels) versus macitentan and tadalafil monotherapies in this PAH patient population."

NDA • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Efficacy And Safety Of Macitentan Tadalafil Fixed Dose Combination In Pulmonary Arterial Hypertension: Results From The Randomized Controlled Phase III A DUE Study (ACC-WCC 2023) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • P3 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Sildenafil citrate, tadalafil and Alzheimer’s risk: new data [Google translation] (Medscape) - "Commenting on the findings for Medscape, The Doctor, Dr. David Knopman...described the study's design as 'impressive' for its efforts to minimize biases, which represented an important limitation in the previous study."

Media quote

A DUE: Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=187 | Active, not recruiting | Sponsor: Actelion | Trial primary completion date: Aug 2022 ➔ Sep 2024

Combination therapy • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A DUE: Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=170 | Active, not recruiting | Sponsor: Actelion | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=252 | Recruiting | Sponsor: Actelion | Not yet recruiting ➔ Recruiting

Enrollment open • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of Fixed Dose Combination of Macitentan/Tadalafil (10 mg/20 mg) Compared to the Reference Free Combination of Macitentan and Tadalafil in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Actelion | Recruiting ➔ Completed

Trial completion

A DUE: Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=170 | Recruiting | Sponsor: Actelion | Trial primary completion date: Apr 2022 ➔ Aug 2022

Combination therapy • Trial primary completion date • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of Fixed Dose Combination of Macitentan/Tadalafil (10 mg/20 mg) Compared to the Reference Free Combination of Macitentan and Tadalafil in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Actelion

New P1 trial