Selexipag Research Articles

A novel HPLC method for selexipag in human plasma and application to a prototype pharmacokinetic study

AbstractA novel simple and cost effective HPLC technique was presented for the quantification of selexipag (SLP) in human plasma sample and the technique's applicability to a pharmacokinetic investigation. Chromatographic separation was achieved with C18 (5 µm × 4.6 mm × 150 mm) column, at 30 °C with isocratic elution, mobile phase composed of solution A (acetonitrile), and solution B (0.5% formic acid) (65:35 v/v) at flow rate 1.2 mL min−1. The linearity range is 10–150 ng mL−1. As sample preparation step human plasma was precipitated with acetonitrile and the detection was provided at 300 nm. The retention time is 8.20 ± 0.02 min. LOD is found to be 3.3 ng mL−1 for drug. The method was applied to the analysis of SLP in human plasma with good recovery as 97.83%. Validation of the studied methods was carried out according to EMA guideline. The new method applied on a prototype pharmacokinetic study by administration of 800 μg SLP to a healthy volunteer and parameters like AUC0–24, AUC0–∞, Cmax, tmax, and t1/2 were assessed.

HEALTH OUTCOMES AND COSTS ASSOCIATED WITH ORAL TREPROSTINIL AND SELEXIPAG ONE YEAR INTO TREATMENT: A UNITED STATES CLAIMS DATABASE ANALYSIS IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

TOPIC: Pulmonary Vascular Disease TYPE: Original Investigations PURPOSE: Previous comparisons of oral treprostinil (TRE) and selexipag (SLX) using real-world data have been limited to short duration follow-up periods or have used models to estimate healthcare costs. This analysis aims to characterize various outcomes and direct healthcare costs for pulmonary arterial hypertension (PAH) patients being treated with TRE or SLX 1-year into treatment. METHODS: A retrospective analysis was completed using the IBM® MarketScan® Research Databases from January 2014 to June 2019. Patients were required to have a pulmonary hypertension inpatient or outpatient medical claim identified by International Classification of Disease Codes (ICD-9-CM: 416.0, 416.8, 416.9; ICD-10-CM: I27.0, I27.20, I27.21, I27.29, I27.81, I27.83, I27.89, I27.9) plus a prescription claim for TRE or SLX. The index date was defined as the day of the first claim for TRE or SLX. Patients were ≥18 years old and required to have a PH medical claim in the 6-month pre-index, continuous health insurance enrollment 6 months pre-index and 12 months post-index. Adherence was defined as having a medication possession ratio (MPR) ≥80% and persistence was defined by continuous therapy in the 1-year follow-up period without a medication gap of ≥60 days. RESULTS: 120 patients in the TRE cohort and 155 patients in the SLX cohort met inclusion criteria. Patients were of similar age (TRE: mean [SD] = 57.0 [16.1] vs. SLX: 57.2 [13.5]), similar sex (TRE: 70% female vs. SLX: 77.4%) and had a similar Charlson Comorbidity Index (CCI) score (TRE: mean [SD] 3.5 [2.6] vs. SLX: 3.1 [2.0]). Concomitant PAH therapies received during the pre-index period were generally similar between cohorts, however, more patients on TRE compared to SLX (11.7% vs. 2.6%, p=0.003) transitioned from parenteral PAH treatment. In the 1-year following treatment, adherence and persistence were comparable: adherence was 83% for TRE and 81% for SLX (p=0.567) and persistence was 53% for TRE and 59% for SLX (p=0.373). Among the patients persistent on therapy at 1-year, median (IQR) annual pharmacy costs were $232,071 ($211,039-$256,402) for SLX compared with $107,511 ($45,647-$186,622) for TRE (p<0.01) representing 116% higher median annual pharmacy costs for SLX. A similar proportion within each group switched to parenteral prostacyclin therapy (TRE: 6.7% vs SLX: 5.2%, p=0.794) or inhaled prostacyclin therapy (TRE: 3.3% vs SLX: 3.2%, p=1.0) in the 1-year follow-up period. After adjusting for baseline differences between cohorts, total mean PAH-related healthcare costs (pharmacy + medical) in the 1-year follow-up period were $350,782 ($307,873-$394,849) for SLX compared to $229,564 ($198,791-$264,944) for TRE (p<0.05). CONCLUSIONS: Real-world claims data show similar utilization and outcomes for TRE and SLX in patients with PAH with notable differences in costs in the 1-year following treatment initiation. CLINICAL IMPLICATIONS: Cost differences between TRE and SLX should be considered when selecting oral prostacyclin therapies given the broader economic impact on the U.S. healthcare system as well as potential costs specific to health insurers, pharmacy-benefit managers, employers, and patients. DISCLOSURES: Employee relationship with United Therapeutics Please note: >$100000 by Peter Classi, source=Web Response, value=Salary Consultant relationship with United Therapeutics Please note: 2020-current Added 04/27/2021 by Bonnie Dean, source=Web Response, value=Grant/Research Support Employee relationship with United Therapeutics Please note: 2017 to Present Added 04/27/2021 by Alex DeRuiter, source=Web Response, value=Salary Employee relationship with Xcenda, LLC Please note: 01/04/2020 Added 04/30/2021 by Henry Lee, source=Web Response, value=Salary Employee relationship with United Therapeutics Corporation Please note: >$100000 by Kellie Morland, source=Web Response, value=Salary Employee relationship with Xcenda LLC Please note: Jan 1, 2020 Added 04/27/2021 by Dana Stafkey-Mailey, source=Web Response, value=UT provided Xcenda Fin Support Employee relationship with United Therapeutics Corporation Please note: 11 Months Added 04/27/2021 by Benjamin Wu, source=Web Response, value=Salary

TRANSITIONING FROM INHALED ILOPROST TO ORAL SELEXIPAG: A CASE REPORT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: The TRANSIT-1 study looked into transition from inhaled Treprostinil to oral Selexipag (SXP) over the course of 16 weeks[1]. To our knowledge, similar published studies or case series regarding transition from inhaled Iloprost (ILO) to SXP are not yet available. We report the safe transition of a patient with connective tissue disease associated pulmonary arterial hypertension (CTD-PAH) from ILO over to SXP. CASE PRESENTATION: 52 y/o woman with SLE-SSc overlap, Raynauds syndrome, CTD-PAH, & resolved past APLA-related PEs on indefinite warfarin, had been on Bosentan 125mg BID & ILO 5mcg 6 inhalations a day for many years. Patient’s CTD-PAH had been stable at WHO FC 2. She had minimal adverse effects from her current medication regimen. Recently, patient expressed a preference for SXP over ILO. Transition was planned based on GRIPHON study[2] . Parallel up-titration of SXP with down-titration of ILO was performed, while patient continued to take Bosentan. For the 1st week, SXP was started at 200mcg BID in addition to usual 6 inhalations daily ILO. SXP was increased by 200mcg BID per week, while ILO was decreased by 3 inhalations per week. By 3rd week, patient took 600 mcg BID of SXP only, her highest tolerable dose. Throughout the transition, patient was in regular communication with the provider & a visiting specialty pharmacy nurse. Adverse reactions reported were nausea and episodic vomiting, which resolved with time & supportive care. Patient maintained her WHO FC & oxygenation, & had no clinical signs of right heart failure. DISCUSSION: The efficacy adverse profile for SXP against placebo is similar to ILO[2-4]. No head to head comparison is available for both drugs. TRANSIT-1 reported side-effect of muscle bleeding for a patient on warfarin. Our patient didn’t report any such event. TRANSIT-1 study continued their parallel titration for 8 weeks, followed by close monitoring for 4 weeks. In contrast, our patient safely stopped her ILO by the 2nd week, while continued the up-titration of SXP to tolerance. CONCLUSIONS: Our case report suggests that a relatively rapid & safe transition from ILO over to SXP is possible in clinically stable patients with CTD-PAH & relatively better preserved functional status. Reference #1: Frost, A., et al., Safety and tolerability of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension: Results from the TRANSIT-1 study. J Heart Lung Transplant, 2019. 38(1): p. 43-50. Reference #2: Sitbon, O., et al., Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med, 2015. 373(26): p. 2522-33. Reference #3: Olschewski, H., et al., Inhaled Iloprost for Severe Pulmonary Hypertension. New Engl J Med, 2002. 347(5): p. 322-329. DISCLOSURES: No relevant relationships by Sajeer Bhura, source=Web Response No relevant relationships by William Gibbons, source=Web Response

New Oral Agent for Pulmonary Arterial Hypertension

In the last decade, several oral agents have become available for treating patients with pulmonary arterial hypertension (PAH). The newest such agent is selexipag (Uptravi; FDA-approved December 21, 2015), an oral selective intrapulmonary prostacyclin-receptor agonist. Selexipag potentially could delay initiation of therapy with intravenous (IV) prostacyclin. In this …