Long-term Safety and Efficacy of Imatinib in Pulmonary Arterial Hypertension: Results From a Pilot Open-Label Extension Study.

SESSION TYPE: DVT/PE/Pulmonary Hypertension Posters IPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PMPURPOSE: PAH is a life-threatening disease with poor prognosis. Imatinib inhibits the PDGF signaling pathway, which appears important in PAH pathogenesis.METHODS: 59 patients symptomatic on approved PAH-specific therapies entered a 24-week, randomized, double-blind, placebo-controlled, pilot study (imatinib 200-400mg daily, n=28; placebo, n=31). 42 patients completed the 24-week study, and 22 entered an open-label extension (OLE) with imatinib. 31 patients received compassionate use imatinib for 4-26 months between 24-week study completion and OLE entry. Only serious AEs were reported during the compassionate use phase. Compassionate use patients considered clinically stable or improved continued into the OLE. 6 minute walk distance (6MWD) and safety are assessed in the OLE.RESULTS: By 18 May 2011, 15 patients continued the OLE (discontinuations: lack of efficacy, n=2; AEs, n=3; death, n=2). Mean±SD 6MWD change from 24-week study baseline was 47±59 (n=20), 53±66 (n=14), 54±63 (n=16), 63±49 (n=15) and 53±62m (n=15) at OLE screening and following 6, 12, 18, and 24 months OLE treatment, respectively. Improvements were comparable to 24-week study completion with imatinib (mean change from baseline: 52m). OLE AEs in ≥20% patients included nasopharyngitis (55%), respiratory infection (46%), vertigo (36%), edema (32%), nausea (27%), cough (23%), edema peripheral (23%), pyrexia (23%). Serious AEs were reported in 9 patients; 2 events in 1 patient were suspected study-drug related (increased blood creatinine, fluid retention). 1 patient receiving compassionate use imatinib had a subdural hematoma after 10 months; the patient recovered and continued into the OLE. 2 patients in the OLE died from cardiac failure (neither suspected study-drug related).CONCLUSIONS: 6MWD was sustained in patients remaining on imatinib in the OLE. AEs were as expected for imatinib in the patient population studied. Assessments every 6 months provide additional data regarding benefits and risks of imatinib in PAH. Imatinib is currently not approved for PAH treatment.CLINICAL IMPLICATIONS: Imatinib may provide a new option for treating advanced PAH.DISCLOSURE: Hossein-Ardeschir Ghofrani: Consultant fee, speaker bureau, advisory committee, etc.: Received honorariums for consultations and/or speaking at conferences from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis.He is member of advisory boards for Bayer HealthCare AG, Pfizer, GSK, Actelion, Ergonex, Lilly, Merck, Encysive, and Ergonex. , Grant monies (from sources other than industry): He has also received governmental grants from the German Research Foundation (DFG), Excellence Cluster Cardiopulmonary Research (ECCPS), State Government of Hessen (LOEWE), and the German Ministry for Education and Research (BMBF).Nicholas Morrell: Grant monies (from industry related sources): Research grant from Novartis, lecture fees from Novartis, Pfizer, ActelionMarius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: Fees for lectures/consultations from Actelion, Bayer, Gilead, GSK, Lilly, Pfizer, NovartisShelley Shapiro: Grant monies (from industry related sources): I receive grant funding from the following companies: Actelion, Ikaria, Gilead, Medtronics, United Therapeutics, Bayer, Consultant fee, speaker bureau, advisory committee, etc.: I am on the speakers bureau for the following companies: United Therapeutics, Gilead, Actelion. I consult for Gilead, United Therapeutics, Novartis.Debbie Quinn: Employee: An employee of the study sponsor (Novartis)Oliver Schmidt: Employee: An employee of the study sponsor (Novartis)A phase III study of imatinib in PAH has recently completed; however, imatinib has not yet been approved for the treatment of PAH. Imatinib has an indication in oncology.University Hospital Giessen and Marburg GmbH, Giessen, Germany.