AVI BioPharma, Inc. reported confirmatory data supporting the Phase II clinical trial data on its NeuGene antisense drug Resten-NG. In September 2003, AVI reported a 75per cent reduction in the restenosis rate from angiographic analysis at six months. Further analysis of the vessel lumen diameter and vessel wall thickness by Intravascular Ultrasound (IVUS) supports the angiographic data.
A multicentre clinical trial evaluated the safety and effectiveness of Resten-NG in patients at high risk of cardiovascular restenosis following angioplasty and stent placement. Resten-NG inhibits the expression of the c-myc gene, which plays a key role in the development of the pathology leading to restenosis.
Fifty-seven patients were enrolled in the trial, known as the AVAIL study, and were randomized into three groups: a control arm, a subtherapeutic dose (3 mg) treatment arm and a therapeutic dose (10 mg) treatment arm. Patients in the therapeutic dose and subtherapeutic dose treatment arms received the drug via a coronary delivery catheter directly to the site of angioplasty and stent placement.
As presented and reported in September, the primary efficacy endpoint was angiographic analysis at six months. The restenosis rate was 33.3per cent in both the control and subtherapeutic dose treatment arms, and 8.3per cent in the therapeutic dose treatment arm. This 75per cent reduction in the rate of restenosis was statistically significant (p=0.02).
The secondary endpoint of the study was late loss, which is the decrease in vessel lumen diameter at six months. The therapeutic dose treatment arm showed a significant reduction of late loss and lesion length compared with the control arm and the subtherapeutic treatment arm. There were no increases in toxicity or adverse events in either of the treatment arms. The therapeutic dose treatment arm also experienced a lower rate of target lesion revascularization than the other arms.
The IVUS data confirmed these results. In addition, these data suggest a dose response benefit of increased lumen diameter and decreased vessel wall thickness, which was not observed in the previous data.
"These results provide additional data supporting the safety and efficacy of AVI's antisense therapeutics in treating cardiovascular disease," said Patrick L Iversen, PhD, senior vice president of R&D at AVI. "The patients treated in this trial were at high risk for restenosis, giving us the ability to evaluate efficacy with a small sample size. These data increase our confidence that Resten-NG provided a substantial benefit for these high-risk patients."
In August, AVI initiated a Phase II clinical study of Resten-NG delivered using AVI's proprietary microbubble delivery system. The study will evaluate efficacy and safety of Resten-NG delivered systemically with AVI's microbubble preparation, compared with angioplasty and stent placement alone. Successful systemic delivery of Resten-NG could make the drug available for broad application with stent placement and for multiple applications after angioplasty. AVI plans to initiate a Phase III clinical trial in Europe with Resten-NG in the first quarter of 2004.
AVI BioPharma develops therapeutic products for the treatment of life-threatening diseases using two technology platforms: third-generation NeuGene antisense drugs and cancer immunotherapy. AVI's lead NeuGene antisense compound is designed to target cell proliferation disorders, including cardiovascular restenosis, cancer and polycystic kidney disease. In addition to targeting specific genes in the body, AVI's antiviral programme uses NeuGene antisense compounds to target single-stranded RNA viruses, including West Nile virus, SARS coronavirus, calicivirus, and hepatitis C. AVI's second technology, Avicine, is a therapeutic cancer vaccine with late-stage trials planned for the treatment of pancreatic cancer.