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

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: Jul 2029 ➔ Sep 2030

Trial completion date • 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

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; Not yet recruiting; Sponsor: Actelion

Clinical • New P3 trial • 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=280 | Recruiting | Sponsor: Actelion | Trial completion date: Feb 2028 ➔ Sep 2029

Trial completion date • 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: Jan 2027 ➔ May 2027

Trial completion date • 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=280 | Recruiting | Sponsor: Actelion | Trial completion date: Mar 2029 ➔ Sep 2030

Trial completion date • 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

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: Sep 2029 ➔ Feb 2028

Trial completion date • 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=280 | Recruiting | Sponsor: Actelion | Trial completion date: Feb 2028 ➔ Mar 2029

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

Multidisciplinary Perioperative Management of Oral Cavity Squamous Cell Carcinoma in an Adult with Eisenmenger Syndrome: A Case Report (AHNS 2026) - "Case Presentation: A 56-year-old man with congenital heart disease complicated by Eisenmenger syndrome (VSD-related, WHO functional class II) on continuous oxygen (3 L/min) and double pulmonary hypertension therapy (Opsynvi – macitentan/tadalafil) was referred for evaluation of a progressive tongue lesion concerning for SCC. Oral cavity cancer in patients with Eisenmenger syndrome presents unique perioperative hazards where successful outcomes depend heavily on multidisciplinary coordination of perioperative care."

Case report • Clinical • Head and Neck Cancer • Heart Failure • Hypotension • Oncology • Oral Cancer • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

In brief: Embryotoxicity REMS removal for endothelin receptor antagonists. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Long-term Treatment of Single-tablet Combination of Macitentan and Tadalafil in Pulmonary Arterial Hypertension (PAH): Final Results From the A DUE Open-label Extension (ATS 2025) - P3 | "Adult PAH patients randomized to M/T FDC, macitentan, or tadalafil during the DB were transitioned to the OL, receiving M/T FDC. The vast majority of patients were alive at the end of the study. Improvements in 6MWD and NT-proBNP observed in the DB with M/T FDC were maintained during the 24-month OL."

Clinical • Late-breaking abstract • Anemia • Cardiovascular • Hematological Disorders • Hepatology • Hypotension • Pulmonary Arterial Hypertension • Respiratory Diseases • NPPB

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

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

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

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