Uptravi Injection (selexipag IV) / J&J, Nippon Shinyaku - LARVOL DELTA

Fatty Acid Metabolism and CPT2 Genotype May Influence Selexipag Responsiveness in Pulmonary Arterial Hypertension (AHA 2025) - "However, the mechanisms underlying inter-individual differences in treatment response remain unclear.Objective: To identify clinical and molecular determinants associated with selexipag responsiveness in patients with PAH. We evaluated 21 patients aged ≥16 years with PAH who received selexipag at Hokkaido University Hospital between 2021 and 2024. The rs1799821 AA genotype in CPT2 may contribute to impaired mitochondrial fatty acid oxidation and suppressed endogenous prostacyclin production, potentially leading to increased responsiveness to selexipag. Altered expression of ATP citrate lyase, fatty acid synthase, and CPT1C may further affect lipid metabolism and contribute to inter-individual variability in treatment response."

Cardiovascular • Metabolic Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases • ACVRL1 • FASN

Efficacy and safety of selexipag based triple combination targeted drug therapy in chinese patients with pulmonary arterial hypertension (ESC-WCC 2025) - "Objective Selexipag, an oral prostacyclin receptor agonist, has been shown to be safe and effective for the treatment of pulmonary arterial hypertension (PAH). Conclusions Triple-targeted drug therapy containing selexipag can be safely and effectively used in Chinese PAH patients, significantly enhancing exercise capacity, improving right heart function and optimizing risk stratification. Selexipag-based initial triple therapy may potentially offer superior benefits in improving risk stratification compared to sequential add-on therapy for PAH patients."

Clinical • Cardiovascular

A real-world study on selexipag for pulmonary arterial hypertension: a single-center retrospective study (ESC-WCC 2025) - " We retrospectively investigated 97 consecutive patients with PAH who received selexipag between 2016 and 2022. In the real-world setting of patients with PAH, selexipag demonstrated improvements in hemodynamics, exercise capacity, and risk classification and did not add newly defined safety signals. These findings are supportive to the efficacy and tolerability of a unique oral PGI₂ receptor agonist selexipag for the favorable management of PAH."

Real-world • Real-world evidence • Retrospective data • Cardiovascular • Heart Failure

10-year Data on Oral Selexipag: Long-Term Survival, Safety, and Dosing Insights in Pulmonary Arterial Hypertension (PAH) from the GRIPHON Study and Its Open-Label Extension (OLE) (ISHLT 2025) - P3 | "We present the final long-term safety, tolerability and survival data for patients treated with selexipag in these studies.Methods Patients were randomized to selexipag and titrated to individualized doses in GRIPHON (double-blind [DB]) (NCT01106014); those who entered its OLE (NCT01112306) were followed for adverse events (AE) and survival up to end of study.Results Of the 574 patients randomized to DB selexipag, 330 continued to receive selexipag in the OLE. Kaplan-Meier survival estimates for the overall population and by dose subgroups are shown in the Figure.Conclusion These data represent the most comprehensive long-term safety, tolerability, and survival data for selexipag and provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with prior observations."

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

Safety and Efficacy of Selexipag for Pediatric Pulmonary Arterial Hypertension in Japanese Patients　- An Open-Label Phase 2 Study. (PubMed, Circ J) - "The efficacy and safety of selexipag in Japanese pediatric patients with PAH were demonstrated."

Journal • P2 data • Cardiovascular • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

The Role of Intravenous Selexipag in Managing PAH and Bridging Gaps in Oral Treatment: A Narrative Review. (PubMed, Ther Clin Risk Manag) - "Given the risks of treatment interruption and the complexity of managing PAH, this review provides essential insights into the practical use of IV selexipag as a bridging therapy. Furthermore, it calls for larger clinical trials to refine dosing strategies, explore long-term outcomes, and identify patient populations most likely to benefit from IV selexipag."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial). (PubMed, Eur Respir J) - P3 | "SELECT was discontinued for futility, as no treatment effect on the primary endpoint (PVR) was observed. Safety data were consistent with the established safety profile of selexipag, with no new safety signals identified."

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

Safety and Effectiveness of Selexipag in Pediatric Pulmonary Hypertension: A Retrospective Multi-Center Cohort Study. (PubMed, J Pediatr) - "In a large, multi-center cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring."

Journal • Retrospective data • Cardiovascular • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Selexipag for patients with pulmonary hypertension associated with lung disease: A preliminary study. (PubMed, Respir Investig) - "Selexipag was effective in half of the PH-LD cases, emphasizing higher BMI and lower PaO2/FiO2 as possible indicators for favorable response. Since selexipag starting at a low dose with subsequent titration may reduce the risk of early adverse events, it can be considered a treatment option for PH-LD. Further large-scale studies are warranted to confirm these findings."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Langerhans Cell Histiocytosis • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis

Long-term data on efficacy and safety of selexipag for scleroderma digital vasculopathy. (PubMed, J Rheumatol) - "We observed a sustained efficacy of selexipag on SSc digital vasculopathy during one year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy."

Journal • Cardiovascular • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Intravenous Selexipag Uptitration for Decompensated Right Ventricular Failure in Pulmonary Arterial Hypertension: A Novel Approach (ATS 2024) - "Transitioning to the oral formulation improved convenience and facilitated continued therapy post-discharge. Further study is warranted to evaluate the efficacy, safety, and long-term outcomes of this approach."

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

PULMOEAST: A Comprehensive Analysis of Pulmonary Hypertension in Eastern India. (PubMed, Cureus) - "Among the vasodilator regimen, two patients received Selexipag. However, the diverse etiologies, limited access to PH-specific resources, and lack of widespread awareness within the region continue to pose substantial challenges for patients. The study underscores the need for refined diagnostic approaches, cost-effective management strategies, collaborative care initiatives, and enhanced patient education to optimize PH care and improve outcomes in eastern India."

Journal • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Four-strata risk assessment in pulmonary arterial hypertension (PAH) patients treated with selexipag in real-world settings: Insights from EXPOSURE (ERS 2023) - "In this prevalent population, the majority (74–81%) received selexipag as part of triple combination therapy. During the exposure period, 47% (7/15; n=12) of all hospitalisations were PAH-related in low risk patients, 54% (37/69; n=39) in intermediate-low, 53% (58/109; n=62) in intermediate-high, and 71% (51/72; n=46) in high risk; death occurred in 1 (1%), 7 (4%), 22 (12%) and 23 (21%) in the 4 risk strata, respectively. Applying the recent ESC/ERS risk assessment indicated that in clinical practice, selexipag is initiated across all 4-risk strata, with about half of patients being at low or intermediate-low risk.; Cell and molecular biology; Pulmonary function testing; General respiratory patient care; Epidemiology; Respiratory intensive care; Public health; Physiology"

Clinical • Real-world • Real-world evidence • Cardiovascular • Critical care • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

The Efficacy and Safety of Selexipag as an Add-On to Standard-of-Care Therapy in Patients With Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension After Surgical and/or Interventional Treatment (SELECT) (ATS 2023) - P3 | "Adults (≥18-≤85 years) with CTEPH were randomized (1:1) to receive selexipag (titrated from 200 µg to 1600 µg twice-daily in weekly increments of 200 µg until individual maximum tolerated dose) or placebo. There were no safety concerns. SELECT was the first randomized controlled trial in CTEPH to be conducted globally with advanced SoC for CTEPH."

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

[VIRTUAL] Severe Pulmonary Arterial Hypertension in a Patient with a History of Phenylpropanolamine Use (ATS 2021) - "She was recently diagnosed with PAH by an outside pulmonologist who started her on triple combination therapy that included sildenafil, macitentan, and selexipag...She was managed with non-invasive ventilation, intravenous vasopressors, inotropes, intravenous bumetanide drip, and she was transitioned from selexipag to intravenous treprostinil with rapid dose up titration...She was transitioned to subcutaneous treprostinil before she was discharged home. Phenylpropanolamine is a drug with a similar structure to amphetamine that was withdrawn from the US market in 2000...Also, there is a report of a fatal case of PAH in a child who was treated with high doses of phenylpropanolamine that was contained in cold medicine. While our case does not serve to establish causality, it highlights a possible association for clinicians to consider."

Clinical • Fibrosis • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Pulmonary Arterial Hypertension • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

[VIRTUAL] Selexipag Titration and Dosing Patterns in Patients with Pulmonary Arterial Hypertension (PAH) in a Real-World Clinical Setting: Insights from the EXPOSURE Study (ATS 2021) - "These analyses include all patients receiving selexipag with follow-up data. With a median duration of 7.3 weeks, the observed titration period is in line with GRIPHON and the selexipag prescribing information. Approximately 25% of patients had further dose adjustments following titration."

Clinical • Real-world evidence • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study. (PubMed, Respir Res) - P3 | "Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions."

Clinical • Journal • P3 data • PK/PD data • Hypertension • Pain • Pulmonary Arterial Hypertension • Respiratory Diseases

Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE. (PubMed, J Heart Lung Transplant) - P=N/A | "Real-world, US-based patients with PAH initiating selexipag typically have WHO FC II/III disease and are at intermediate risk, despite receiving PAH-specific treatment. Selexipag was prescribed as part of a combination regimen in most patients. The study identified no unexpected adverse effects."

Clinical • Journal • Real-World Evidence • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases • Rheumatology

Comparative effectiveness of oral prostacyclin pathway drugs on hospitalization in patients with pulmonary hypertension in the United States: a retrospective database analysis. (PubMed, Pulm Circ) - "The study cohort included 99 patients receiving oral treprostinil and 123 receiving selexipag. Compared with oral treprostinil, selexipag was associated with a 46% lower risk of all-cause hospitalization (hazard ratio 0.54, 95% confidence interval 0.31, 0.92; P = 0.02), a 47% lower risk of pulmonary hypertension-related hospitalization (hazard ratio 0.53, 95% confidence interval 0.31, 0.93; P = 0.03), a 42% lower all-cause hospitalization rate (rate ratio 0.58, 95% confidence interval 0.39, 0.87; P = 0.01), and a 46% lower pulmonary hypertension-related hospitalization rate (rate ratio 0.54, 95% confidence interval 0.35, 0.82; P = 0.004). This study suggests that selexipag is associated with lower hospitalization risk and rate than oral treprostinil."

HEOR • Journal • Retrospective data • Hypertension • Pulmonary Arterial Hypertension • Respiratory Diseases

[VIRTUAL] REAL-WORLD DATA FOR SELEXIPAG IN PATIENTS WITH CONNECTIVE TISSUE DISEASE-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION: A SPHERE (SELEXIPAG: THE USERS DRUG REGISTRY) ANALYSIS (CHEST 2020) - P=N/A, P3 | "In SPHERE, CTD-PAH disease and treatment characteristics were consistent with previously reported data. Compared to baseline, the majority of pts had either improved or stable risk status with treatment. Outcomes for CTD-PAH pts receiving selexipag in the real-world setting were broadly similar to those of IPAH."

Clinical • Real-World Evidence • Hypertension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Respiratory Diseases • Rheumatology

[VIRTUAL] A SUCCESSFUL RAPID TRANSITION FROM ORAL TREPROSTINIL TO SELEXIPAG IN A PATIENT WITH PULMONARY ARTERIAL HYPERTENSION AND LIMITED CUTANEOUS SYSTEMIC SCLEROSIS (CHEST 2020) - "Her PAH regimen included macitentan, sildenafil, and oral treprostinil at a total daily dose of 19 mg (7, 6, and 6 mg)...The target dose of selexipag was based on our center’s experience with treprostinil 5 ng/kg/min SQ/IV = selexipag 200 mcg BID, and oral treprostinil 1 mg TID = treprostinil 5-6 ng/kg/min SQ/IV in a 70 kg person...Selexipag dose remains at 1400 mcg BID. We hypothesized that a rapid transition between oral treprostinil and selexipag is possible using a transition plan formulated by integrating prior experience with rapid transitions for a) selexipag and subcutaneous treprostinil; b) subcutaneous treprostinil and orenitram; and c) intravenous epoprostenol and infusion treprostinil... To our knowledge this is the first described rapid transition from oral treprostinil to selexipag. The patient tolerated transition without hemodynamic instability, excessive side effects, or need for rescue epoprostenol therapy. This case demonstrates that rapid transition..."

Clinical • Fibrosis • Hypertension • Immunology • Pain • Pulmonary Arterial Hypertension • Scleroderma • Systemic Sclerosis

[VIRTUAL] Hospitalization Rates and Association with Survival Risk at Baseline in Patients with Pulmonary Artery Hypertension (PAH) Receiving Selexipag in Real-World (RW) Clinical Practice (ISPOR-EU 2020) - P=N/A | "Compared to low risk patients, risk increased by 70% (HR [95% CI]: 1.70 [1.16, 2.50], p-value 0.0070) in intermediate risk patients and by 199% (HR [95% CI]: 2.99 [2.10, 4.25], p-value <0.0001) in high risk patients. CONCLUSIONS SPHERE analysis demonstrates that intermediate/high risk at baseline is associated with higher hospitalization and re-hospitalization rates compared to low risk and that REVEAL 2.0 risk category is prognostic of hospitalization outcome in the real-world setting."

Clinical • Real-World Evidence • Hypertension • Pulmonary Arterial Hypertension