The Appraisal-Trial: Evaluating RESTEN-MPTM in Patients with Bare Metal Stent De Novo Native Coronary Artery Lesions

Abstract

Neointimal hyperplasia is one of the key components of the restenotic process. The aim of this study was to evaluate the efficacy and safety of a microbubble delivery of c-myc antisense peptide in reducing restenosis after coronary stenting in de novo stenosis with intravascular ultrasound. A Multi-Link Zeta bare metal stent was implanted in de novo coronary artery lesions (RD ≥ 2.5-≤ 4.0 mm; TL ≥ 15-≤ 30 mm in length). Serial intravascular ultrasound analyses were performed in 25 lesions. A dose of 16mg RESTEN-MP TM (AVI BioPharma supplied by Global Therapeutics LLC) was intravenously administered after stenting and again 24 hours later. In three centres in Germany a total of 50patients (51 lesions) were enrolled, 34 in Essen, 13 in Coburg and 3 in Heidelberg. Before stenting, the minimal lumen diameter (MLD) and length of stenosis were determined. 84% (43/51) of the lesions were either Type B2 or C lesions. At six-month follow-up, angiography was performed. Generally the neointimal proliferation was minor. Major adverse cardiac events (MACE) were 10.0% after 6 months and 21.9% after 12 months. The target lesion revascularization was 15.6%, the target vessel revascularization 18.8% after 12 months. Of the 34 patients studied at six-months in the IVUS sub-study, six patients required target lesion revascularization (TLR). Binary restenosis rate by intravascular ultrasound was 26 ± 4%. Generally the neointima proliferation was minor and open vessel lumen could be demonstrated during follow-up. Microbubble delivery of c-myc antisense seems to be effective in reducing neointimal tissue proliferation without the problem of late stent thrombosis. Neointima proliferation seems to be attenuated but not eliminated. MACE was not increased in this study population.

Strategies to Inhibit Myc and Their Clinical Applicability

“…A Phase I trial of Resten-NG carried out by AVI BioPharma enabled the determination of its bioavailability in solid tumor patients and established the feasibility of using PMOs in human cancer (Devi et al, 2005 ). Moreover, local delivery was feasible and safe in a related target disease, cardiovascular restenosis that involves neointimal hyperplasia (Kipshidze et al, 2003 , 2004 ) and a Phase II study reported positive results following local delivery (Kipshidze et al, 2007 ; Philipp et al, 2012 ).…”

MYC: there is more to it than cancer

“…It was successfully tested in a rabbit balloon injury model ( Kipshidze et al, 2002 ) and porcine restenosis model ( Kipshidze et al, 2003 ; Kipshidze et al, 2002 ) with promising results: significant reduction of the neointimal area with concomitant MYC inhibition. Although this was further validated in a Phase II trial with positive results ( Philipp, 2012 ), the drug was not developed beyond this point.…”