ralinepag (APD811) / United Therapeutics Corp, Pfizer, Everest Medicines - LARVOL DELTA

United Therapeutics Corporation Reports Record Second Quarter 2025 Financial Results (Businesswire) - "Tyvaso DPI record total revenue of $315 million, reflecting 22 percent growth over the second quarter of 2024....Double-digit, year-over-year revenue growth for Nebulized Tyvaso, Orenitram, and Unituxin with record quarterly revenue for Orenitram; Phase 3 TETON 2 study of Nebulized Tyvaso in idiopathic pulmonary fibrosis is complete; data expected in September 2025; phase 3 TETON 1 data expected in the first half of 2026; Enrollment for the phase 3 ADVANCE OUTCOMES study of ralinepag in pulmonary arterial hypertension is complete; data expected in the first half of 2026."

Enrollment closed • P3 data • Sales • Idiopathic Pulmonary Fibrosis • Neuroblastoma • Neuroendocrine Tumor • Pulmonary Arterial Hypertension

Risk Improvements in Ralinepag Open-Label Extension (ERS 2025) - No abstract available

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

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: United Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology

Safety and pharmacokinetics of ralinepag, a novel oral prostacyclin receptor agonist. (PubMed, JHLT Open) - "One received a single dose of ralinepag IR (30 µg) followed by single ascending doses of XR (60, 120, and 180 µg), and the other received single ascending doses of selexipag (200, 400, and 600 µg). Ralinepag XR has a half-life suitable for once-daily dosing. The reduced Cmax and delayed Tmax contributes to lower peak-to-trough fluctuations and may provide favorable effects for sustained efficacy and improved tolerability."

Journal • PK/PD data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Ralinepag Treatment to Achieve and Maintain REVEAL Lite 2 Low Risk Status: Interim Results of ADVANCE EXTENSION (ATS 2025) - "CONCLUSIONS Treatment with ralinepag in the OLE produced early and sustained REVEAL Lite 2 risk improvements after experiencing a CWE, with a substantial proportion of participants maintaining or achieving low risk status. Sponsored by United Therapeutics"

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

Developing Models for New Drugs in PAH: A Pharmacokinetic Simulation of Ralinepag (ISHLT 2025) - P3 | "The model also accurately predicted blood plasma concentrations consistent with those observed in the phase 2 study with patients with PAH.Conclusion The accuracy of this model across multiple doses and formulations suggests that it will be applicable in analyzing results from the ongoing phase 3 ADVANCE OUTCOMES study. Beyond simulating PK, we plan to extend the model to link with variables such as hemodynamics and exercise capacity, with potential utility to calculate dosing equivalencies for transition from other PAH therapies to ralinepag."

PK/PD data • Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension (clinicaltrials.gov) - P3 | N=1000 | Enrolling by invitation | Sponsor: United Therapeutics | Trial completion date: Sep 2024 ➔ Dec 2026 | Trial primary completion date: Sep 2024 ➔ Dec 2026

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

United Therapeutics Corporation Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "'both TETON studies in idiopathic pulmonary fibrosis are enrolled, facilitating data starting the second half of this year; ralinepag, our potentially best-in-class once-daily oral prostacyclin agonist, will generate data next year'...Total Tyvaso revenues grew by 19 percent to $415.9 million in the fourth quarter of 2024, compared to $350.6 million in the fourth quarter of 2023...Total Tyvaso revenues grew by 31 percent to $1,620.4 million in 2024, compared to $1,233.7 million in 2023...The growth in Remodulin revenues resulted from an increase in U.S. Remodulin revenues, driven by an increase in quantities sold. The growth in Orenitram revenues resulted from an increase in quantities sold and, to a lesser extent, a price increase."

Clinical data • Commercial • P3 data • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Respiratory Diseases

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: United Therapeutics | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

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

New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review. (PubMed, Cureus) - "Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat...The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Initial Long-term Data From a Phase 3 Open-label Extension Study (ROR-PH-303) Evaluating Ralinepag for the Treatment of Pulmonary Arterial Hypertension (Advance Extension) (ATS 2024) - P3 | "Ralinepag has produced sustained, durable improvements in 6MWD and WHO FC, and reduced risk scores. The safety profile of ralinepag is similar to that reported in previous studies. Data from this Phase 3 OLE study demonstrate the benefit-risk ratio of ralinepag remains unchanged and positive."

Clinical • P3 data • Cardiovascular • Hypertension • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

"Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial." F. Torres, H. Farber, A. Ristic, et al. Eur Respir J 2019; 54: 1901030. (PubMed, Eur Respir J) - No abstract available

Journal • P2 data

A Study of Ralinepag in Healthy Chinese Adult Subjects (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Everstar Medicines (Shanghai) Limited | Recruiting ➔ Completed

Trial completion

Ralinepag Phase II Open-Label Extension Study in Patients with Pulmonary Arterial Hypertension. (PubMed, Adv Ther) - "Ralinepag produced sustained, durable improvements in 6MWD along with durable reductions in PVR and a manageable AE profile. Most participants continuing treatment with ralinepag maintained functional measures throughout the OLE and those switching from placebo to ralinepag often experienced functional improvements."

Clinical • Journal • P2 data • Cardiovascular • Hypertension • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: United Therapeutics | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

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

A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH (clinicaltrials.gov) - P3 | N=10 | Terminated | Sponsor: United Therapeutics | Active, not recruiting ➔ Terminated; Sponsor decision

Trial termination • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • NPPB

Reproducibility of CPET variables in subjects with pulmonary arterial hypertension: Preliminary data from ADVANCE CAPACITY (ERS 2023) - "ADVANCE CAPACITY is a 28-week global, multicenter, randomized, double-blind, placebo-controlled study using VO2peak from a cardiopulmonary exercise test (CPET) to evaluate the efficacy of ralinepag (a selective, oral non-prostanoid, IP receptor agonist) to increase exercise capacity in subjects with pulmonary arterial hypertension (PAH)... CPET variables are highly reproducible in PAH patients and are robust endpoints to assess exercise capacity in PAH.; Pulmonary rehabilitation; Pulmonary function testing; Physiology; Imaging"

Clinical • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: United Therapeutics | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

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

A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH (clinicaltrials.gov) - P3 | N=10 | Active, not recruiting | Sponsor: United Therapeutics | Recruiting ➔ Active, not recruiting | N=193 ➔ 10 | Trial completion date: Jan 2025 ➔ Jul 2023 | Trial primary completion date: Jan 2025 ➔ Jul 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • NPPB

A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH (clinicaltrials.gov) - P3 | N=193 | Recruiting | Sponsor: United Therapeutics | Trial completion date: Sep 2023 ➔ Jan 2025 | Trial primary completion date: Sep 2023 ➔ Jan 2025

Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • NPPB

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: United Therapeutics | N=700 ➔ 1000

Enrollment change • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in Subjects with Pulmonary Arterial Hypertension (ADVANCE OUTCOMES) (ATS 2022) - P3 | "ADVANCE OUTCOMES will assess whether ralinepag can improve function, delay disease progression, and prolong survival in subjects with PAH. Funded by United Therapeutics Corporation"

Clinical • P3 data • Hypertension • Infectious Disease • Novel Coronavirus Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Long-Term Data from Study APD811-007, an Open-Label Extension Study Evaluating Ralinepag for the Treatment of Pulmonary Arterial Hypertension (ATS 2022) - P2 | "The overall safety profile of ralinepag was similar to that reported in the parent study and data from the OLE study demonstrate the benefit-risk ratio of ralinepag remains unchanged and positive."

Clinical • Hypertension • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients (clinicaltrials.gov) - P3; N=700; Recruiting; Sponsor: United Therapeutics; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology

[VIRTUAL] Biological quality control and core laboratory considerations for CPET in a clinical trial of ralinepag in patients with pulmonary arterial hypertension: ADVANCE CAPACITY (ERS 2021) - "Recruitment has started and emerging data will be presented. This trial has the potential to offer a method for CPET use in future global clinical trials."

Clinical • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases