April 1, 2009 (Orlando, Florida) — A bioresorbable material injected via catheter into infarcted tissue post-AMI may prove to be a promising preventive strategy for limiting infarct expansion and improving left ventricular function--potentially boosting survival rates, researchers reported here at the American College of Cardiology 2009 Scientific Sessions. According to investigators, who also invented the product, the biomaterial known as BL-1040 (BiolineRX, Jerusalem, Israel) has many advantages over cell-based therapies in development with the same goals. But unlike cells or growth factors, the low-viscosity liquid is simple to produce, can be used off the shelf, and is nonimmunogenic.
BL-1040 is a bioresorbable calcium-alginate–based polymer that is liquid at room temperature but polymerizes to form a gel once injected, via coronary catheterization, in the damaged tissue. Describing how the product works, presenter Dr Jonathan Leor (Ben-Gurion University, Beer-Sheva, Israel) explained that the biomaterial, once injected, serves to replace the missing extracellular matrix that is damaged after MI and provide temporary structural support for infarct repair, preventing the tissue degradation and pathological LV remodeling that takes place as a result.
"The rationale behind this is that everything you do to make the infarct thicker and stronger can reduce wall stress and then can prevent infarct expansion and global LV dilatation," Jonathan Leor said. "We're not talking about regeneration, we're not creating new heart muscle, we're talking about creating a better, smaller, thicker scar."
Preclinical and First-In-Human Findings Promising
Leor showed 60-day autopsy findings from animal studies showing normal LV size in pigs with induced AMIs, treated with BL-1040, as compared with dilated LV in pigs who did not receive BL-1040 injections. Likewise, pig and dog models of AMI showed no wall thinning, no LV remodeling, no LV dysfunction, and a 50% reduction in mortality at six months. In separate preclinical work, again in dogs, investigators saw a 50% reduction in mitral regurgitation at six-month follow-up, as compared with dogs not treated with BL-1040.
Moving ahead with a first-in-human clinical trial, Leor and colleagues have launched a study at nine sites in Germany and Belgium, enrolling 30 patients, all of whom have had a first, extensive MI, an ejection fraction of less than 45%, and at least four akinetic segments. Early results in the first five patients suggest that the procedure itself, performed at all sites by interventional cardiologists, was feasible and safe at six months, with no adverse events, no complications, no arrhythmias, and no cardiac-enzyme elevations. There are also early signs that ejection fraction, NT-proBNP, and anatomical parameters appear to have stabilized or improved.
Though early, "Our work suggests [we have] a catheter-based, acellular option to facilitate infarct stabilization and to repair and prevent adverse LV remodeling after MI," Leor said.
A spokesperson for the company, Dr Shmuel Tuvia, said that the FDA is already "very enthusiastic" about the product and has told the company that the first-in-human data, once follow-up in all 30 patients is completed, will be accepted as adequate pilot data for its investigational device exemption (IDE) submission. Investigators are currently planning a larger randomized, multicenter, placebo-controlled study.
Commenting on the study after its presentation in a panel discussion during the late-breaking clinical-trials session, Dr Douglas Mann (Washington University, St Louis, MO), who was not involved with the study or the product, congratulated the investigators, saying, "We all want to be enthusiastic, but we have to be cautious because this is early . . . but all the efficacy signals are there." One thing to clarify, he noted, was the extent to which some of the benefits are coming merely from reperfusion during PCI. But Mann also pointed out opportunities to use BL-1040 as a biologically "smart" platform, containing genes, growth factors, or drugs, something Leor said his team is already exploring. So far, however, adding additional biomaterials to the platform has not produced any benefits over and above those seen with BL-1040 alone.
Dr Marvin Konstam (Tufts University School of Medicine, Boston, MA), another member of the discussion panel (first noting that he is a consultant to the company), said that approaches like this one offer obvious appeal over more invasive strategies, such as ventricular "restraint" devices and LVADs, down the road. "This obviously is a much more limited intervention and is very appealing," he said. "We have to take this presentation with a grain of salt, but I'm very encouraged by the preclinical data, because the ability to impact mechanically on remodeling, in a noninvasive way, focused on a specific region," is very appealing.
Heartwire from Medscape © 2009 Medscape, LLC
Cite this: ACC 2009: Bioresorbable Gel, Injected Into Infarcts, Holds Promise Post-MI for Preventing Remodeling and Improving Survival - Medscape - Apr 01, 2009.