Data from three drugs in Isis’ lipid franchise were presented in three invited presentations and a poster presentation at the 2014 European Society of Cardiology Congress held in Barcelona, Spain from August 30 to September 3, 2014. Isis has created a lipid franchise of antisense drugs designed to provide effective and safe therapeutic options to treat patients with lipid disorders. This franchise is composed of one commercialized drug and several other drugs in clinical development designed to treat cardiovascular conditions by reducing specific lipid parameters that are risk factors for cardiovascular disease. Data presented include:
John Kastelein, M.D., Ph.D., Professor of Medicine, Chairman of the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, presented data from a retrospective analysis of 104 patients who enrolled in the long-term extension study of KYNAMRO after having completed one of the KYNAMRO Phase 3 studies. The retrospective analysis examined the rate of major adverse cardiovascular events, or MACE, in patients during the two years immediately prior to KYNAMRO treatment and compared it to the rate of MACE after one year of treatment with KYNAMRO. MACE is a composite of clinical events that typically reflect safety and effectiveness in cardiovascular research. In this study, MACE was defined as myocardial infarction, stroke, unstable angina and revascularization procedures. In this retrospective analysis, the rate of MACE in patients treated with KYNAMRO for one year was adjudicated by an independent committee and compared to the rate of MACE in the same patients based on their medical history prior to treatment with KYNAMRO. The retrospective analysis showed a five-fold reduction in the rate of MACE in patients during the one year of KYNAMRO treatment in comparison to the previous two years. Prior to receiving KYNAMRO, the proportion of patients that had experienced a MACE was 25.72/1000 months. In stark contrast, during the one year of treatment with KYNAMRO, the proportion of patients that had experienced a MACE dropped dramatically to 4.85/1000 months. The statistically significant reduction (p <0.0001) in the rate of MACE demonstrated the potential for therapeutic benefit of KYNAMRO in patients with homozygous FH, the most aggressive form of familial hypercholesterolemia.
Dr. Kastelein also presented an overview of the results from Isis’ broad Phase 2 program for ISIS-APOCIIIRx. In all patient groups studied in the Phase 2 program, treatment with ISIS-APOCIIIRx consistently reduced apoC-III by up to 88 percent, triglycerides by up to 71 percent, and increased HDL-cholesterol by up to 78 percent, with a positive effect on non-HDL. In all of the clinical studies, ISIS-APOCIIIRx had a tolerability profile supportive of continued development. Indeed, Isis is currently evaluating ISIS-APOCIIIRx in a Phase 3 study in patients with familial chylomicronemia syndrome and plans to initiate additional Phase 3 studies for patients with severely elevated triglycerides. Vickie Alexander, Ph.D., Director, Clinical Development at Isis also presented these data in a poster as part of the Lipoproteins in Cardiovascular Prevention session.
In a separate presentation, Sotirios Tsimikas, M.D., Professor of Medicine and Director of Vascular Medicine at the University of California, San Diego and Vice President of Clinical Development and Leader of Cardiovascular Franchise at Isis, presented data from the Phase 1 study of ISIS-APO(a)Rx in healthy volunteers with baseline elevated lipoprotein (a) or Lp(a) levels. Lp(a) is recognized as an independent risk factor for coronary artery disease. In this study, treatment with ISIS-APO(a)Rx produced dose-dependent reductions of up to 89 percent in Lp(a). The tolerability profile for ISIS-APO(a)Rx in this study supported further development. Isis is currently evaluating ISIS-APO(a)Rx in a Phase 2 study in patients with elevated Lp(a) levels.