Toronto, Ontario (PRWEB) January 26, 2012
Matrizyme Pharma Corporation (Matrizyme) today announced the completion of its phase I clinical program for its lead product, MZ-004, for the treatment of coronary chronic total occlusions (CTOs). The program consisted of treating patients with CTOs that had a previously failed attempt by percutaneous coronary intervention (PCI). The program involved a dose escalation portion in which 20 patients with CTOs were treated with single doses of MZ-004 from 300 – 1,200 µg and a pharmacokinetic sub-study in which another eight patients with CTOs were dosed at the highest dose level (1,200 μg). The results of the dose escalation portion of the program were published today in the journal Circulation. 2012; 125:522-528.
The results reported in Circulation, demonstrated that just one treatment of MZ-004 (300 – 1,200 μg) in patients with CTOs who had previously failed a PCI attempt, was safe, well-tolerated and facilitated guide wire crossing in 15 of the 20 patients (75%). A soft-tip guide wire was either the sole or predominant guide wire used in 75% of successful crossings. Computed tomographic angiography at three months post dosing showed no late complications and patent stents in all successfully treated CTOs. Importantly, a statistically significant anginal improvement was observed with a reduction in Canadian Cardiovascular Society class from baseline to three months (2.5±0.6 versus 0.9±0.9; P<0.001). In the program as a whole, 21 of the 28 patients treated with MZ-004 had a successful PCI following the dosing.
The paper concludes that local delivery of MZ-004 into coronary CTOs is feasible and safe with encouraging guide wire crossing results in previously failed cases.
“The results are very encouraging and bare out the early work, that has also been published, on the effects of MZ-004 in preclinical CTO models”, says Dr. Bradley Strauss, the founder of Matrizyme and the lead author of the publication. “The acceptance of the data for publication in such a prestigious journal as Circulation shows that alternative approaches for the treatment of CTOs, which currently are under treated, is not only needed, but the use of MZ-004 in this application is novel in its approach.”
Matrizyme has already met with FDA and Health Canada to discuss the overall development program for MZ-004 and moving forward with the continued development of MZ-004.
CTOs are defined as totally occluded arteries with TIMI 0 or 1 flow and ≥3 month duration (where it is known). Angiographic studies have shown CTOs are present in approximately 20% of subjects with coronary artery disease (CAD). In many cases, the actual age of the CTO is not precisely known since there may have been no definite clinical event, such as a heart attack. Successful revascularization of a coronary CTO improves angina, left ventricular function, and possibly even reduces mortality. Despite the benefits of therapy, currently <10% of subjects with coronary CTOs are treated with angioplasty. The remaining subjects are either referred for coronary artery bypass graft surgery (25%), or persist with medical therapy and/or exercise regimens (65% CAD), both of which have significant limitations.
Successful PCI requires the passage of a small guide wire through the tissue obstructing the lumen. Procedural success rates in stenotic (but non-occluded) coronary artery lesions are in excess of 95%. However, procedural success rates for CTOs in the majority of centers are only in the 60-70% range. Difficulty in safely crossing the occlusion with the guidewire is the most common technical challenge, accounting for about 95% of failures. This technical hurdle, along with the prolonged radiation exposure, high contrast loads (with risk of contrast nephropathy) and vascular perforations all contribute to why angioplasty is not used more frequently as a treatment for CTOs.
About Matrizyme Pharma Corporation
Matrizyme is a Toronto based, privately held biopharmaceutical company, focused on the development of novel technologies to facilitate the treatment of chronic total occlusions. Matrizyme’s lead development product is MZ-004. More information about Matrizyme or MZ-004 can be found at http://www.matrizyme.com.