Medical Device Daily

Device and pharmaceutical company Angiotech Pharmaceuticals (Vancouver, British Columbia) has made good on what it promised earlier this year: to file for FDA clearance of its anti-infective 5-Fluorouracil-coated (5-FU) Central Venous Catheter (CVC) before year's end.

The company reported yesterday that it has filed for FDA 510(k) clearance for the device, which is the latest product in its pipeline to help curb the spread of deadly hospital infections such as the Methicillin-resistant Staphylococcus aureus (MRSA) "superbug" - a former media topic, which seems to have cooled in recent weeks.

Angiotech joins Acrymed (Portland), Pure Bioscience (San Diego) and C.R. Bard (Murray Hill, New Jersey) in developing applications to reduce these deadly infections.

But Angiotech isn't going down the traditional "silver-coated" path these other med-tech companies have treaded in developing their devices to stop infections. It competitors have looked to silver and its bacteria-arresting abilities to line the devices for optimal patient safety. But Angiotech believes that 5-FU, a well-known and approved compound, has even greater potential to be used as a coating to prevent catheter-related infections as effectively as use of silver or the standard antiseptics and antibiotics.

5-FU principally acts as a thymidylate synthase inhibitor, meaning that it interrupts the action of this enzyme which is a critical factor in the synthesis of the pyrimidine thymine — important in DNA replication. Some of its principal uses are in combating colorectal cancer and pancreatic cancer, in which it has been the established form of chemotherapy for decades. (Platinum-containing drugs are a recent addition.)

The principle behind using 5-FU on a CVC is that the drug appears to effectively interrupt the colonization of an implanted medical device by those micro-organisms that typically gain entrance to the bloodstream via the local skin penetration of implanted catheters. This reduction in colonization by bacteria may have a net effect of reducing biofilm burden on the implanted catheters, making them less likely to serve as reservoirs for additional infection.

CVC's are usually used in the treatment of critically ill patients for extended periods of time to administer fluids, drugs, and nutrition, as well as facilitate frequent blood draws. But one of the major complications associated with CVC implantation is infection, which can occur when bacteria contaminate the catheter.

In looking for a drug that would work as effectively as traditional antiseptics and antibiotics at preventing catheter-related infections, without the risk of encouraging the development of a "super bug" that could spread throughout a hospital, Angiotech said that it found 5-FU, an approved anti-cancer drug. The advantage of using 5-FU is that it has no clinical application as either a systemic antibiotic or a hospital antiseptic, so patients don't have any additional risk when using it, according to the company.

"We are pleased to complete the submission of a 510(k) application to the FDA for our 5-FU CVC, as we believe this represents another important step towards commercializing this product line and developing our 5-FU anti-infective platform," William Hunter, president/CEO of Angiotech, said in a statement.

Back in July the company completed enrollment of 960 patients in the clinical trial of its 5-FU CVC, which was one of the largest CVC studies ever conducted. It was designed as a randomized, single-blind, active-controlled, two-arm, multicenter clinical study. The primary objective was to compare the Angiotech 5-FU CVC to a leading antiinfective catheter with regards to preventing bacterial colonization.

The company said it plans to present the pivotal study results at the "37 Critical Care Congress" hosted by the Society of Critical Care Medicine (Mount Prospect, Illinois), Feb. 2-6, at the Hawaii Convention Center.

Angiotech said it expects the 5-FU CVC to be its first product line to be completely researched, developed and commercialized using internal resources, personnel and technologies, many of which were obtained through previous acquisitions completed by the company.

Pending the receipt of necessary regulatory approvals, Angiotech said it anticipates commercial launch of the 5-FU CVC product line sometime next year.

MRSA, along with other infections that find comfortable homes in hospitals, is the fourth leading cause of death in the U.S., which cost an average of $57,000 per patient for diagnosis and treatment and can cost hospitals between $28 billion and $30 billion annually in extended care and treatment, according to the Centers for Disease Control and Prevention (Atlanta).

In the U.S., specifically, the cost per catheter-related infection can range from $3,700 to $29,000. In addition, the CDC has raised concerns about the overuse of traditional antibiotics, which can contribute to an increase in the antibiotic resistance of bacteria.

Angiotech develops treatments for diseases or complications associated with device implants, surgical interventions and acute injury.