Medical Device Daily Associate

Angiotech Pharmaceuticals (Vancouver, British Columbia), supplier of the drug component paclitaxel to Boston Scientific's (Natick, Massachusetts) blockbuster Taxus drug-eluting stent (DES) product, is continuing its advance into the drug/device arena with its report last week that it has launched a U.S. pivotal study examining an anti-microbial central venous catheter (CVC).

The study enrolled its first patient in Rapid City, South Dakota, and will involve about 600 patients at 20 centers in the U.S. The multi-center trial is designed to evaluate the efficacy of a CVC coated with the drug 5-Flourouracil (5-FU), a non-traditional anti-infective agent, to prevent bacterial colonization.

CVCs are catheters that are usually inserted into critically ill patients for extended periods of time to administer fluids, drugs and nutrition, as well as to facilitate frequent blood draws.

One of the complications associated with CVC implantation is infection, which can occur when bacteria contaminate the surface of the catheter. CVC infections that progress to bloodstream infections or septicemia can become life threatening.

The CVC trial is a randomized, single-blind, active-controlled, two-arm, multi-center clinical study. The lead trial site is the University of Massachusetts Memorial Medical Center (Worcester), with Stephen Heard, MD, as principal investigator. The primary objective of the study is to compare the Angiotech CVC catheter to a leading anti-infective catheter.

Other objectives will include prevention of local catheter-related infections or widespread bloodstream infections. Assuming favorable study results, Angiotech intends to seek FDA 510(k) clearance for the product.

Todd Young, MD, Angiotech's vice president of investor relations and communications, told Medical Device Daily in an e-mail exchange that as part of its discovery process, the company systematically screens approved drugs for new applications, using adjusted dosing and application techniques to determine the optimal combined product.

As an example, he pointed to the Taxus DES device, using Angiotech's drug and polymer coating. Paclitaxel was first approved as a systemic chemotherapy agent but was found by Angiotech to prohibit cell proliferation when used in very small doses.

About 5-FU, Young said it is "one of the oldest FDA-approved chemotherapy drugs available. Historically, 5-FU was originally used as a systemic antibiotic, but it was never used locally."

He added: "Through its extensive screening process, Angiotech found 5-Fu to be the best candidate for local infective use."

Angiotech said it chose 5-FU because of its ability to kill bacteria such as gram positive Staphylococcus aureus and gram negative Pseudomonas aeruginosa, which can be lethal pathogens.

The company said it chose this compound also because of its "unique and valuable ability to help prevent formation of biofilm," a slimy coating that bacteria produce to protect them from traditional antibiotics. Additionally, the company noted that 5-FU doesn't build bacterial resistance as do traditional antibiotics.

"Ultimately," Young said, "Angiotech hopes the CVC to be but one product of an extensive anti-infective platform, if 5-FU is successful in the trial."

The opportunity for this particular drug/device combination is much less than coronary stenting but still very large. About 3.5 million CVC catheters are used in the U.S. annually leading to roughly 250,000 CVC-related infections and an estimated 40,000 deaths. The cost of caring for these patients is estimated to be as high as $56,000 per infection, according to estimates by Angiotech.

Angiotech is developing the drug 5-FU, used for the treatment of cancer, as a non-traditional anti-infective in order to address concerns voiced by the Center for Disease Control (CDC; Atlanta) regarding overuse of traditional antibiotics, which can contribute to an increase in the antibiotic resistance of bacteria.

Traditional anti-infective coatings are being used more frequently each year and are currently used, on an annualized basis, on about 20% of CVC products implanted.

Jorge Reyno, MD, an infectious disease specialist at Rapid City Regional Hospital in South Dakota where the first patient was recently enrolled, said, "We are excited to be participating in a study addressing such a pervasive and critical issue. Hospital-based infections, which include CVC infections, are a vexing and potentially lethal problem that demands a better solution."

"The use of 5-FU as an anti-infective coating to prevent catheter-related bloodstream infections is innovative and unique," said Heard, who in addition to being the principal investigator of the CVC trial also chairs the department of anesthesiology at University of Massachusetts Memorial Medical Center and the University of Massachusetts Medical School (Worcester). "In vitro data demonstrate that 5-FU has antibacterial activity similar to current anti-infective catheter surfaces. We are eager to see if these effects impact catheter colonization and bloodstream infection in patients," he added.

While Angiotech has traditionally let other companies focus on the manufacture and sales of devices based on its technology, Young noted that the company has become much more emphatic concerning its intent to take over many of these duties.

"An anti-infective CVC catheter is a good example of a product that Angiotech would be able to manage on its own as a standalone product or out-license if they so chose," he said.

This internalized focus, in which the objective is to grow commercially and operationally to obtain complete control over commercial ownership and the end sale of products, is one of the primary pillars of Angiotech's development strategy.

Therapeutic areas for this approach include interventional vascular, orthopedics, and general, such as the anti-infective CVC, anti-adhesion products, tumor resection treatments and drug-loaded sutures.

Young said Angiotech's recent $14 million cash acquisition of Edwards Lifesciences' (Irvine, California) ePTFE graft division (MDD, Dec. 2, 2005) to manufacture its own vascular wrap/graft product was a "significant stepping stone" toward its internal focus to control more of its own commercial destiny.

"The anti-infective CVC initiative puts Angiotech in yet another key area [anti-infectives] in which it believes its approach will greatly improve current available options for patients," said Young. He also noted that the CVC study "is the largest trial to date that Angiotech has undertaken on its own."