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Slide Presentations: Wednesday, October 26, 2011 |

Imatinib Improves Exercise Capacity and Hemodynamics at 24 Weeks as Add-on Therapy in Symptomatic Pulmonary Arterial Hypertension Patients: The IMPRES Study FREE TO VIEW

Marius Hoeper, MD; Robyn Barst, MD; Robert Bourge, MD; J. Feldman, MD; A. Frost, MD; Nazzareno Galie, MD; Miguel Angel Gomez Sanchez, MD; Ekkehard Gruenig, MD; Paul Hassoun, MD; Nicholas Morrell, MD; Andrew Peacock, MD; Toru Satoh, MD; Gérald Simonneau, MD; Victor Tapson, MD; F. Torres, MD; Keith Liu, PhD; Debbie Quinn, MD; Hossein Ghofrani, MD
Chest. 2011;140(4_MeetingAbstracts):1045A. doi:10.1378/chest.1216523
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Abstract

PURPOSE: Pulmonary arterial hypertension (PAH) involves enhanced pulmonary vascular remodeling and proliferation. Currently approved therapies for PAH target the prostacyclin, endothelin and nitric oxide pathways. Imatinib is a novel orally-active anti-proliferative therapy in clinical development for PAH. The IMPRES study evaluated its efficacy, safety and tolerability over 24 weeks in patients with persistent PAH despite optimized therapy with established PAH therapies.

METHODS: Double-blind, randomized, parallel-group study comparing oral imatinib (200 mg once daily, increased to 400 mg once daily after 2 weeks if well tolerated) with placebo in patients with pulmonary vascular resistance (PVR) ≥800 dynes/sec/cm-5 despite receiving at least two PAH-specific therapies. Primary endpoint was change in 6-minute walk distance (6MWD), between baseline and Week 24. Secondary endpoints included changes in hemodynamics, NT-pro-BNP, time to clinical worsening (TTCW) and safety and tolerability.

RESULTS: 202 patients were randomized (103 imatinib; 99 placebo). Mean age 48 years (18-77), mean duration of PAH 5.3 years, 67.7% WHO Class III and mean 6MWD 344 m (337 vs 351 m for imatinib and placebo, respectively). 67.0% imatinib and 81.8% placebo patients completed and entered a separate extension study. Placebo-corrected treatment effects at Week 24 vs baseline included: improved 6MWD (32 m; p=0.002), PVR (-379 dynes/sec/cm-5, p<0.001), cardiac output (0.88 L/min, p<0.001) and NT-pro-BNP values (-45.10 pmol/L, p=0.04). The hazard ratio for TTCW was 1.16 (imatinib-placebo, p=0.563). The overall incidence of adverse events (AEs) was similar for imatinib and placebo (97% vs 96% respectively). Serious AEs were more frequent with imatinib than placebo (44% vs 30%). There were three deaths in each group.

CONCLUSIONS: Imatinib significantly improved 6MWD, CO, PVR and NT-pro-BNP. SAEs were higher in the imatinib group as expected for this population and class of drug. Long-term outcomes will be explored in extension studies.

CLINICAL IMPLICATIONS: Imatinib may provide a new therapeutic option for selected PAH patients, symptomatic on two or more established PAH therapies.

DISCLOSURE: Marius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: MMH has received honoraria for speaking at conferences and/or consultation fees from Actelion, Bayer, GSK, Lilly, Pfizer and Novartis.

Robyn Barst: Consultant fee, speaker bureau, advisory committee, etc.: RJB has received honoraria for consulting and/or speaker's bureau from: Actelion, Eli Lilly, Gilead, Ikaria, Merck, Novartis and Pfizer.

Robert Bourge: Grant monies (from industry related sources): RCB has received grant support from Novartis.

J. Feldman: Consultant fee, speaker bureau, advisory committee, etc.: JF serves as a consultant and speaker for United Therapeutics and Gilead Sciences.

A. Frost: Consultant fee, speaker bureau, advisory committee, etc.: AF has received honoraria for consulting from Bayer,& Gilead Sciences; has received honoraria for speaking from Gilead Sciences and United Therapeutics; has attended meetings for which she has received travel reimbursement and honoraria for speaking/participatioin from Actelion, Pfizer and Gilead Sciences. Dr Frost has also participated in ad boards, as a consultant, and on speakers’ bureau for Actelion., Gilead, and Pfizer., Other: AF has been reimbursed for time, travel, and participation in the Entelligence Young Investigators Grant award program, and a multicenter PH registry - REVEAL - both of which are sponsored by Actelion., Grant monies (from industry related sources): AF, as P.I. (Principal Investigator), has undertaken numerous IRB FDA-approved pharmaceutical studies in pulmonary hypertension for which Baylor College of Medicine has received funds from Gilead, Pfizer, Actelion, United Therapeutics, Bayer, and Novartis.

Nazzareno Galie: Consultant fee, speaker bureau, advisory committee, etc.: NG has been involved with Steering Committee activities for Eli Lilly and company, Actelion, Pfizer, Bayer-Schering, and GlaxoSmithKline and Novartis; Has been a paid lecturer, for Actelion, Eli Lilly and company, Pfizer, Bayer-Schering, and GlaxoSmithKline., Grant monies (from industry related sources): NG has done contract research for Actelion, Pfizer, United Therapeutics, Bayer-Schering, GlaxoSmithKline and Novartis.

Miguel Angel Gomez Sanchez: Grant monies (from industry related sources): MAGS has received research contracts (grants) from Pfizer, GSK, Bayer Schering, Schering, Actelion, Gilead, Lilly Icos, United Therapeutics and Lung Rx., Consultant fee, speaker bureau, advisory committee, etc.: MAGS has received fees for speaking, organizing education and consulting from Pfizer, GSK, Bayer Shering, Actelion and Lilly Icos.

Ekkehard Gruenig: Consultant fee, speaker bureau, advisory committee, etc.: EG has received honoraria for consulting or giving talks from Actelion, Bayer, GSK, Lilly, Pfizer, Grant monies (from industry related sources): EG has undertaken IRB FDA-approved pharmaceutical studies in pulmonary hypertension for those the hospital received funds from Actelion, Bayer, GSK, Lilly, Novartis, Pfizer and United Therapeutics.

Paul Hassoun: Consultant fee, speaker bureau, advisory committee, etc.: PMH is on the advisory boards of Novartis, Pfizer, and Gilead.

Nicholas Morrell: Consultant fee, speaker bureau, advisory committee, etc.: NWM has received consultancy fees from Novartis., Grant monies (from industry related sources): NWM has received a research grant from Novartis.

Andrew Peacock: Consultant fee, speaker bureau, advisory committee, etc.: AJP has received honoraria for speaking; support for research and assistance with travel from GSK, Novartis, Eli Lilly, Pfizer, Actelion and Bayer, Grant monies (from industry related sources): AJP has received honoraria for speaking; support for research and assistance with travel from GSK, Novartis, Eli Lilly, Pfizer, Actelion and Bayer

Toru Satoh: Consultant fee, speaker bureau, advisory committee, etc.: TS has received honoraria for speaking support for research and assistance with travel from GSK, Pfizer, Actelion and Nippon Shinyaku Co.,Ltd, Grant monies (from industry related sources): TS has received honoraria for speaking support for research and assistance with travel from GSK, Pfizer, Actelion and Nippon Shinyaku Co.,Ltd

Gérald Simonneau: Consultant fee, speaker bureau, advisory committee, etc.: GS has been involved with Steering Committee activities for Eli Lilly and company, Actelion, Pfizer, Bayer-Schering, and GlaxoSmithKline and Novartis; Has been a paid lecturer, for Actelion, Eli Lilly and company, Pfizer, Bayer-Schering, and GlaxoSmithKline, Grant monies (from industry related sources): GS has done contract research for Actelion, Pfizer, United Therapeutics, Bayer-Schering, GlaxoSmithKline and Novartis.

Victor Tapson: Consultant fee, speaker bureau, advisory committee, etc.: VFT has received consulting fees and honoraria from Actelion, Bayer, Gilead, Novartis, United Therapeutics. , Grant monies (from industry related sources): VFT has received research funding involving pulmonary hypertension from Actelion, Bayer, Gilead, Novartis, United Therapeutics.

F. Torres: Consultant fee, speaker bureau, advisory committee, etc.: FT has received honoraria for speaking from Actelion, Gilead Sciences and United Therapeutics; has attended meetings for which she has received travel reimbursement and honoraria for speaking/participatioin from Actelion, United Therapeutics and Gilead Sciences. Has participated in ad boards, as a consultant, and on speakers’ bureau for Actelion., United Therapeutics, Gilead, and Pfizer., Grant monies (from industry related sources): FT, as P.I. (Principal Investigator), has undertaken numerous IRB FDA-approved pharmaceutical studies in pulmonary hypertension for which UT Southwestern Medical Center has received funds from Gilead, Pfizer, Actelion, United Therapeutics, Bayer, and Novartis.

Keith Liu: Employee: KL is an employee of Novartis

Debbie Quinn: Employee: DQ is an employee of Novartis.

Hossein Ghofrani: Grant monies (from industry related sources): HAG has received research grants from Bayer Schering, Pfizer., Consultant fee, speaker bureau, advisory committee, etc.: HAG honoraria payments from Bayer Schering, Pfizer, Actelion, Encysive, and GlaxoSmithKline; he has served as a consultant and/or advisory board member for Bayer Schering, Pfizer, Actelion, Encysive, Ergonex, and GlaxoSmithKline.

This is a pivotal clinical trial designed to investigate the efficacy, safety and tolerability of the investigational therapy imatinib in the treatment of pulmonary arterial hypertension. Imatinib is however already licensed for the treatment of a range of oncology indications.

11:30 AM - 12:45 PM


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