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Pulmonary Vascular Disease |

Riociguat in Combination With Prostacyclin Analogs for the Treatment of Pulmonary Arterial Hypertension (PAH): A Subgroup Analysis of the PATENT Studies

Ioana Preston; Nicholas Hill; Hossein Ardeschir Ghofrani; Marius Hoeper; David Langleben; Carmine Dario Vizza; Sylvia Nikkho; Kai Vogtlaender; Pavel Jansa
Author and Funding Information

Pulmonary, Critical Care, and Sleep Division, Tufts University School of Medicine, Boston, MA; University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center of Lung Research (DZL), Giessen, Germany; Clinic for Respiratory Medicine, Hannover Medical School, Member of the German Center of Lung Research (DZL), Hannover, Germany; Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada; Department of Cardiovascular and Respiratory Disease, La Sapienza University of Rome, Rome, Italy; Global Clinical Development, Bayer Pharma AG, Berlin, Germany; Bayer Pharma AG, Wuppertal, Germany; Clinical Department of Cardiology and Angiology of the First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic


Chest. 2015;148(4_MeetingAbstracts):922A. doi:10.1378/chest.2276665
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Abstract

SESSION TITLE: Hot Topics in PAH

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Wednesday, October 28, 2015 at 04:30 PM - 05:30 PM

PURPOSE: To assess the safety and efficacy of riociguat in patients with PAH receiving prostacyclin analogs (PCAs) in the Phase III PATENT-1 study and the PATENT-2 long-term extension.

METHODS: In PATENT-1, patients with PAH (n=443) were randomized to placebo, riociguat up to 2.5 mg tid, or riociguat up to 1.5 mg tid (exploratory) for 12 weeks. Efficacy data from the riociguat 2.5 mg and placebo groups are presented. Patients completing PATENT-1 without ongoing riociguat-related serious AEs were eligible to enter PATENT-2, during which all patients received open-label riociguat up to 2.5 mg tid.

RESULTS: At PATENT-1 baseline, 31 patients were receiving PCAs (45% iloprost [n=12 inhaled; n=1 intravenous; n=1 oral]; 32% oral beraprost sodium; 23% subcutaneous treprostinil). Of these, 20 were randomized to riociguat up to 2.5 mg tid, 4 to riociguat up to 1.5 mg tid, and 7 to placebo. In PCA-pretreated patients at PATENT-1 Week 12, mean±SD 6MWD (primary endpoint) had increased by 56±84 m in the riociguat group and decreased by 40±78 m in the placebo group, giving a least-squares mean treatment effect of +101 m (95% CI 27-176 m). PCA-pretreated patients in the riociguat group also showed greater improvements in PVR (-259±260 vs +61±198 dyn·s·cm-5), NT-proBNP (-203±872 vs +578±2782 pg/mL), and WHO FC (30 vs 14%) versus placebo. The safety profile of riociguat in the PCA-pretreated subgroup was comparable to the overall population. Common AEs (pooled riociguat groups vs placebo) included dizziness (25 vs 0%), headache (21 vs 14%), hypotension (17 vs 0%), and nausea (17 vs 29%). Serious AEs in the riociguat groups included single cases of right ventricular failure, hemoptysis, and hypotension. Improvements in 6MWD and WHO FC in the PCA-pretreated subgroup persisted in the PATENT-2 extension; at 2 years in the total patient population, 6MWD had increased by 48±142 m from PATENT-1 baseline (n=17), and WHO FC had improved/stabilized/worsened in 22/67/11% of patients (n=18). Riociguat was well tolerated in PCA-pretreated patients in PATENT-2, with no new safety signals identified. Further analyses of the efficacy of riociguat in combination with different types and doses of PCAs will be presented.

CONCLUSIONS: Addition of riociguat to patients with PAH receiving PCAs was well tolerated and led to improvements in several clinical endpoints versus placebo.

CLINICAL IMPLICATIONS: These data suggest that riociguat in combination with PCAs could be an effective treatment in patients with PAH.

DISCLOSURE: Ioana Preston: Grant monies (from industry related sources): Received grants from Actelion, Grant monies (from industry related sources): Received grants from Gilead, Grant monies (from industry related sources): Received grants from United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Received personal fees from Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Received personal fees from Gilead, Consultant fee, speaker bureau, advisory committee, etc.: Received personal fees from United Therapeutics Nicholas Hill: Grant monies (from sources other than industry): NIH, NHLBI, Grant monies (from industry related sources): Actelion, Bayer, Gilead, Reata Pharmaceuticals, Lung Biotechnology, United Therapeutics Hossein Ardeschir Ghofrani: Consultant fee, speaker bureau, advisory committee, etc.: Received fees for consultancies from Actelion, Bayer, Ergonex, Gilead, GSK, Merck, Novartis, and Pfizer., Consultant fee, speaker bureau, advisory committee, etc.: Speakers bureaus for Actelion, Bayer, Ergonex, Gilead, GSK, Novartis, and Pfizer. Marius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: Fees for consultations and lectures from Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Fees for consultations and lectures from Bayer, Consultant fee, speaker bureau, advisory committee, etc.: Fees for consultations and lectures from GSK, Consultant fee, speaker bureau, advisory committee, etc.: Fees for consultations and lectures from Pfizer David Langleben: Grant monies (from industry related sources): Grant support from Bayer, Consultant fee, speaker bureau, advisory committee, etc.: Personal fees and non-financial support from Bayer Carmine Dario Vizza: Grant monies (from industry related sources): Received research support from Actelion, Novartis, GSK, Bayer Pharma AG, and Gilead, Consultant fee, speaker bureau, advisory committee, etc.: Received fees for consultancies Bayer Pharma AG, Actelion, GSK, and Utel, Consultant fee, speaker bureau, advisory committee, etc.: Speakers bureaus for Bayer Pharma AG, Actelion, GSK, and Utel Sylvia Nikkho: Employee: Full-time employee of Bayer Pharma AG Kai Vogtlaender: Employee: Full-time employee of Bayer Pharma AG Pavel Jansa: Consultant fee, speaker bureau, advisory committee, etc.: Received fees as investigator for Actelion and Bayer Pharma AG, Consultant fee, speaker bureau, advisory committee, etc.: Received personal fees from AOP and Bayer Pharma AG

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