SESSION TYPE: Late-Breaking Abstracts
PRESENTED ON: Tuesday, October 23, 2012 at 04:30 PM - 05:45 PM
PURPOSE: Riociguat is the first member of a novel class of compounds, the soluble guanylate cyclase (sGC) stimulators. With a dual mode of action, it synergizes with endogenous nitric oxide (NO) and also directly stimulates sGC independent of NO availability. Therefore, riociguat may restore the NO-sGC-cGMP pathway. The Phase III, double-blind, randomized, placebo-controlled PATENT-1 study investigated the efficacy and safety of riociguat in patients with symptomatic pulmonary arterial hypertension (PAH).
METHODS: Treatment-naïve patients and patients pre-treated with endothelin receptor antagonists (ERAs) or prostanoids (inhaled or subcutaneous) were eligible. Patients were assigned to placebo or riociguat administered according to a titration regimen (starting dose: 1 mg three times daily [t.i.d.]; range: 0.5-2.5 mg t.i.d.). The primary outcome was the placebo-corrected change from baseline in 6-minute walking distance (6MWD) at week 12. Secondary endpoints included the change from baseline in pulmonary vascular resistance (PVR), NT-proBNP, functional class, clinical worsening, living with pulmonary hypertension questionnaire and Borg dyspnea score.
RESULTS: Overall, 445 patients were randomized. Preliminary analysis showed an increase in 6MWD from baseline of 35.8 m with riociguat versus placebo (95% CI 20.1-51.5 m, p<0.0001). Predefined exploratory analyses indicated that riociguat improved 6MWD in pretreated patients (+35.7 m [95% CI 15.0-56.3 m]) as well as treatment-naïve patients (+38.4 m [95% CI 14.5-62.3 m]). Significant improvements were also seen in PVR (p<0.0001), NT-proBNP (p<0.0001), functional class (p=0.003), clinical worsening (p=0.0046), living with pulmonary hypertension questionnaire (p=0.002), and Borg dyspnea score (p=0.002). Riociguat was well tolerated and had a favorable safety profile.
CONCLUSIONS: In patients with PAH, riociguat was well tolerated, significantly improved 6MWD, and consistently improved clinically relevant secondary efficacy endpoints.
CLINICAL IMPLICATIONS: Riociguat represents a new treatment option for patients with PAH. Efficacy of riociguat was consistently shown in both treatment-naïve patients and patients pre-treated with ERA or inhaled or subcutaneous prostanoid monotherapy. PATENT-2 will evaluate the long-term safety of riociguat in patients with PAH.
DISCLOSURE: Hossein Ghofrani: Grant monies (from sources other than industry): Hossein A. Ghofrani has received sponsored grants over the past 3 years from the German Research Foundation, Excellence Cluster Cardiopulmonary Research and Germany Ministry for Education and Research, Grant monies (from industry related sources): Hossein A. Ghofrani has received industry-sponsored grants over the past 3 years from Bayer HealthCare AG, Aires, Encysive/Pfizer and Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Hossein A. Ghofrani has relationships with the following drug companies: Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Novartis and GlaxoSmithKline
Nazzareno Galie: University grant monies: Nazzareno Galie has relationships with the following drug companies: Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline and Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Nazzareno Galie has relationships with the following drug companies: Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline and Novartis
Friedrich Grimminger: Consultant fee, speaker bureau, advisory committee, etc.: Friedrich Grimminger has relationships with Bayer AG
Marc Humbert: Consultant fee, speaker bureau, advisory committee, etc.: Marc Humbert has relationships with drug companies including Actelion, Aires, Bayer, GlaxoSmithKline, Novartis, and Pfizer. In addition to being investigator in trials involving these companies, relationships include consultancy service and membership of scientific advisory boards
Anne Keogh: University grant monies: Anne Keogh has received university grant monies from the following drug companies: Actelion, GlaxoSmithKline, Pfizer, United Therapeutics and Bayer
David Langleben: Grant monies (from industry related sources): David Langleben has received industry sponsored grant monies from Bayer, Consultant fee, speaker bureau, advisory committee, etc.: David Langleben has relationships with Bayer
Michael Ochan Kilama: Employee: Michael Ochan Kilama is an employee of Bayer HealthCare, Global Clinical Development. He is the company medical expert (research physician) for the PATENT study.
Dieter Neuser: Employee: Dieter Neuser is an employee of Bayer Pharma AG
Lewis Rubin: Consultant fee, speaker bureau, advisory committee, etc.: Lewis J. Rubin has relationships with the following drug companies: United therapeutics, Actelion, Pfizer, Lung LLC, Gilead, GlaxoSmithKline and Bayer
Riociguat is an investigational new drug currently in process for registration submission to health authorities, after successful finalisation of an RCT in patients with PAH.Department of Internal Medicine, University Hospital Giessen and Marburg, Giessen, Germany