Bioabsorbable Cardiac Matrix Fails in Phase 1 Clinical Trial

A clinical trial known as Preservation 1 examined the use of Bioabsorbable Cardiac Matrix in heart attack patients. Preservation 1 was a double-blinded, placebo-controlled study that examined heart attack patients who had been treated with PCI (percutaneous coronary intervention), which is also known as angioplasty with stent placement.

This clinical trial compared patients who had the bioabsorbable cardiac matrix placed over the dead part of the heart with those who had been treated with sterile saline (placebo). Because it was a phase 1 clinical trial, it tested safety issues rather than efficacy issues.

The bioabsorbable cardiac matrix is initially administered as a liquid that is injected into the heart. Upon contact with damaged cardiac tissue, it undergoes a transition from liquid to gel that provides mechanical support and allows the damaged tissue to heal and form a more compact, tighter scar. A smaller scar should result in improved long-term cardiac function. The gel also resorbs naturally and is excreted from the body within six weeks of injection. The matrix might also be able to support stem cells that migrate to the heart after the heart attack. Therefore, the hope for this trial was that patients who received the bioabsorbable cardiac matrix might show less remodeling or enlargement of the heart after their heart attacks. Patients were given either the placebo of the bioabsorbable cardiac matrix 2-5 days after receiving PCI.

When studied in laboratory rodents, the matrix was administered up to 7 days post-heart attack and it improved survival, prevented the dilation of the left ventricular end systolic and diastolic volume, prevented fractional shortening deterioration and improved mitral regurgitation. Treatment also minimized the systolic wall thinning, all of which are findings consistent with the prevention of progressive expansion of the infarcted area of the heart.

In the Preservation 1 trial, patients were examined six months after treatment, and their left ventricular end diastolic volume index (LVEDVI) was measured. The LVEDVI goes up if the heart is undergoing remodeling. Also patients were given a standard questionnaire (Kansas City Cardiomyopathy Questionnaire) and a six-minute walk test. Adverse reactions that were measured were time until the patients died from heart-related issues, heart-related events, hospitalizations, and time until the first heart-related hospitalization.

Unfortunately, when it came to safety and efficacy, the bioabsorbable cardiac matrix was no better than the placebo. This product, which was called BL-1040, was licensed to a company called Bellerophon in 2009. Prior to this partnership with Bellerophon, BioLineRx invested some $10 million in the development BL-1040. It is a shame that it failed in this trial.

Biolinerx is still eager to test their product as a way to mobilize cells from bone marrow, induce the death of cancer cells, and other potential applications.  While the theory behind this product seems sound, the heart after a heart attack needs more than just a temporary structural support; it needs cells and new vasculature.  If the bioabsorbable cardiac matrix could be laced with stem  cells and the matrix could not only contribute to stem cell survival, but also stem cell efficacy, then this product might really help a damaged heart heal.