XBiotech recently completed a groundbreaking clinical study in cardiovascular medicine. This Phase II randomized, multi-center clinical study evaluated a True Human™ therapeutic antibody MABp1 for its ability to reduce adverse events after balloon angioplasty, atherectomy or stent placement in patients undergoing revascularization procedures for blockage of a major artery (superficial femoral artery or SFA) in the leg. Interim data from this study was submitted to the FDA and resulted in Fast Track designation for this drug development program.
The multi-center study was headed by Hosam El-Sayed MD, Ph.D., RVT, assistant professor of cardiovascular surgery at the Methodist Hospital in Houston, Texas, which is recognized as a national center of excellence for cardiovascular medicine. Patients were particularly monitored for restenosis, or other Major Adverse Cardiovascular Events (MACE), including heart attack or stroke.
Patients undergoing SFA revascularization typically have an overwhelming systemic vascular disease process, and restenosis and other MACE are common, perhaps even inevitable. A challenge in these patients is to prolong patency of vessels and to reduce the occurrence of other MACE in the post revascularization period.
Vascular disease contributes to the most common causes of death in the developed world, and ever more so, in the emerging economic regions. In the late 1980's the pathophysiology of arterial disease began to be understood in terms of a chronic inflammatory process. Since then considerable clinical and experimental evidence has pointed to a role for white blood cells in the progression of atherosclerosis, heart attack and stroke. In the past decade, technology to treat vascular disease has largely centered around angioplasty and the use of stents, to open affected arteries and maintain patency, respectively.
Unfortunately, while achieving overall great success clinically, these methods can sometimes result in only temporary benefit to patients, since treated arteries can re-occlude (i.e. restenosis). Since options for treatment after restenosis are more limited, this represents a particularly important treatment area.
Multiple human and animal studies have demonstrated an association between IL-1α and the progression of atherosclerotic plaques. IL-1α expression in white blood cells has been found to be elevated in patients with both stable and unstable angina compared with healthy individuals. Cells associated with the atherosclerotic plaques, such as foam cells (FC), vascular smooth muscle cells (VSMC) and endothelial cells (EC) show elevated expression of IL-1α; and examination of atherosclerotic plaques from affected arteries of human subjects has demonstrated IL-1α expression on infiltrating white blood cells.
In animals, reduced ability to naturally downregulate IL-1α activity results in massive arterial inflammation with attendant infiltration of white blood cells into artery walls. These animals develop extensive vascular disease, characterized by arterial blockage, aneurysms and heart disease. Death is at an early age.
Using an anti-IL-1α True Human™ antibody to inhibit white blood cell infiltration of the artery may be broadly beneficial to vascular health. In particular, using such an antibody therapy after angioplasty procedure may reduce subsequent arterial inflammation and provide a means to reduce the incidence or severity of restenosis.
Clinical results to date using XBiotechs True Human™ antibody therapy have shown important reduction in the occurrence of restenosis, and reduced incidence of MACE in treated patients compared to controls. These data, together with the FDA Fast Track designation, have supported advancement of the clinical trial program for the treatment of vascular injury and disease.