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New Real-World Observational Analysis of UPTRAVI® (selexipag) Underscores the Importance of Risk Assessment for Treating Pulmonary Arterial Hypertension (PAH) Patients

  • Data from the SPHERE Registry published in the Journal of Heart and Lung Transplantation

SOUTH SAN FRANCISCO, CA – April 6, 2021 – Findings from an analysis of the first 500 patients enrolled in the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry) found more than three-quarters (76%) of pulmonary arterial hypertension (PAH) patients treated with UPTRAVI® (selexipag) either maintained (56%) or reduced (20%) their one-year mortality risk score. The SPHERE results were published in the April issue of the Journal of Heart and Lung Transplantation (JHLT). SPHERE is an ongoing real-world, observational, user registry using two different risk assessment methods that describes the clinical characteristics, outcomes and dosing/titration regimens in patients with PAH who are being treated with UPTRAVI.

PAH is a rapidly progressive disease with no known cure. For individuals with PAH, risk assessment is necessary to evaluate disease progression and inform treatment decisions based on patients’ prognosis.[1] UPTRAVI is an oral prostacyclin pathway agent (PPA) indicated for the treatment of patients with PAH (World Health Organization [WHO] Group I, functional class [FC] II-III) to delay disease progression and reduce the risk of hospitalization. In the pivotal GRIPHON trial, UPTRAVI was proven to reduce the risk of disease progression by 40%.

“Within the PAH treatment paradigm, real-world evidence has become valuable information for physicians to consider when it comes to elevating the standard of care,” said Nick Kim, M.D.*, primary study investigator and professor of medicine at the University of California San Diego. “Findings from the SPHERE analysis reinforce the need for physicians to be conducting routine comprehensive risk assessments and utilizing available tools such as risk calculators to ensure that PAH patients are achieving their treatment goals.”

In treating patients with PAH, routine comprehensive risk assessment is strongly recommended by the 2015 European Society of Cardiology and the European Respiratory Society (ESC/ERS) Guidelines, as there is no single variable that can provide sufficient diagnostic and prognostic information. Additionally, achieving and/or maintaining a low-risk profile is a recommended adequate treatment response for patients with PAH.[2]

In the analysis of the data from the SPHERE registry, risk categories for one-year mortality are assigned to patients using two different assessments, the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) † risk calculators, and PAH patients are classified as low, intermediate or high risk. Results from this analysis showed that at the end of the 18-month follow-up, 19.2% of patients had a lower REVEAL 2.0 risk score, 57.8% experienced no change in their REVEAL 2.0 risk score, and 20.2% noticed an increase in their REVEAL 2.0 risk score. The findings in this analysis were consistent with the COMPERA calculations as well, as 21.4% of patients experienced a positive change in their risk category (moving from a more serious to less serious category), 54.4% maintained their risk category, and 19.4% experienced a negative change in their risk category (moving from a less serious to a more serious category).

SPHERE enrolled patients who were either newly initiated on UPTRAVI (≤60 days before enrollment) or previously received UPTRAVI with documentation of dose titration at study enrollment. Data from this SPHERE analysis suggest that 87.8% of patients titrated UPTRAVI at a slower rate than 200-mcg BID increments, revealing that in the real-world environment patients were titrated less than the recommended titration schedule in the GRIPHON study. [3],[4]

“We’re proud to support SPHERE, as data from this registry furthers our understanding of UPTRAVI within a clinical setting in the U.S.,” said Siân Walker , Head of Medical Affairs, Janssen U.S., Pulmonary Hypertension. “These findings add to the growing body of evidence that demonstrates the need for utilizing risk assessment tools in clinical practice that may optimize the standard of care for patients with PAH.”

Data from SPHERE are limited to what is collected during routine clinical visits, and patients are observed for up to 18 months after enrollment. In this cohort, 94.8% of patients have PAH (WHO Group I), most commonly idiopathic (49.2%) followed by connective tissue disease (CTD)-associated PAH (26.4%). 31.0% and 49.6% of patients have WHO FC II and WHO FC III disease at baseline respectively. There were no new safety signals identified with UPTRAVI in the real-world setting, and the incidence of discontinuation due to UPTRAVI treatment-related adverse events (AEs) remained low in the SPHERE analysis (7.2%). The most common AEs leading to discontinuation were headache (6.5%) and diarrhea (5.1%) in newly initiated patients, and worsening PAH (3.3%) and right ventricular failure (1.9%) in previously initiated patients.

To read the full manuscript and learn more about the SPHERE analysis, please visit

Real-World Data Limitations
Real-world data have the potential to supplement randomized controlled trial data by providing additional information as to how a medicine performs in routine clinical practice. There are limitations, however, and real-world data cannot be used as stand-alone evidence to validate the efficacy or safety of a treatment.

About UPTRAVI® (selexipag) and the GRIPHON Trial
UPTRAVI is an oral selective prostacyclin IP receptor agonist for the treatment of PAH. UPTRAVI is the only globally available oral treatment that works on the prostacyclin pathway with evidence of long-term outcomes. UPTRAVI is available for the treatment of patients with PAH (WHO Group I, FC II-III) in more than 40 countries. In the US, UPTRAVI is indicated for the treatment of PAH to delay disease progression and reduce the risk of PAH-related hospitalization.In Europe, UPTRAVI is indicated for the long-term treatment of PAH in adult patients with WHO FC II–III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 inhibitor (PDE-5), or as monotherapy in patients who are not candidates for these therapies.

The efficacy of UPTRAVI in PAH was established in GRIPHON (Prostacyclin [PGI2] Receptor agonist In Pulmonary arterial HypertensiON), the largest randomized, controlled trial ever conducted in PAH patients. The GRIPHON trial was the first multicenter, long-term, double-blind, placebo-controlled, parallel-group, event-driven Phase 3 study in patients with symptomatic PAH (N=1156; nearly all WHO FC II-III at baseline) evaluating the effects of UPTRAVI (n=574) vs placebo (n=582) targeting the prostacyclin pathway (median duration of exposure 1.4 years, up to 4.2 years). UPTRAVI was shown to delay disease progression and reduce the risk of hospitalization compared with placebo.3 Overall, the most common AEs in the UPTRAVI group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain.3

*Dr. Nick Kim has received research support from Janssen and has served as a paid consultant to the company.
The REVEAL Registry™ is a registered trademark of Actelion Pharmaceuticals Ltd.
Siân Walker Peasegood is an employee of Actelion Pharmaceuticals US, Inc.

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Last Updated: 07-Apr-2021