Liz Hurlburt sheds light on DefenCath, a one of the kind, catheter lock solution

Shots:

Liz Hurlburt, Executive Vice President of Clinical & Medical Affairs at CorMedix discusses the revolutionary prospects of DefenCath, a catheter lock solution to prevent CRBSIs in patients receiving hemodialysis via. CVC
Liz sheds light on a serious unmet need for patients affected with catheter-related bloodstream infections. CRBSIs affect approximately 250,000 people annually who receive treatment with an intravascular device like a CVC
While discussing the roadmap for DefenCath in other indications, Liz shares insights from CorMedix's Phase 3 LOCK IT-100 study results that were published in the Clinical Journal of the American Society of Nephrology (CJASN)

Saurabh: Give a brief overview of DefenCath (a catheter lock solution) which is used in the prevention of Catheter-Related Bloodstream Infections (CRBSIs) in patients receiving hemodialysis via CVC.   

Liz: DefenCath is an investigational catheter lock solution currently in review by the U.S. Food & Drug Administration (FDA) to reduce the incidence of catheter-related bloodstream infections (CRBSIs) in patients with kidney failure receiving chronic hemodialysis through a central venous catheter (CVC). CorMedix developed DefenCath to address a serious unmet need. CRBSIs are one of the most frequent, deadly, and expensive complications of CVCs. It’s estimated that approximately 250,000 CRBSIs occur annually in patients with an intravascular device, such as CVCs. CVCs are necessary to provide life-saving treatments to patients, but clinicians often worry about the inherent risk of infection when using them.

DefenCath is comprised of the anticoagulant heparin and CorMedix’s synthetic proprietary molecule, taurolidine. Taurolidine is a broad-spectrum antimicrobial, meaning it is effective against both gram-positive and gram-negative bacteria, even though it is not an antibiotic and fungi. To date, there has been no known antimicrobial resistance with DefenCath, which is critical given the crisis we’re in in regard to antimicrobial resistance and the over and misuse of antibiotics.

DefenCath is designed to sit in the catheter in between sessions of dialysis or times when a catheter is accessed.

Saurabh: Discuss the study design and results from Phase 3 LOCK IT-100 study that are published in the Clinical Journal of the American Society of Nephrology.

Liz: LOCK-IT-100, was a Phase III, randomized, double-blind, active-controlled, multicenter trial comparing DefenCath to heparin as a catheter lock solution in 806 patients with kidney failure receiving chronic hemodialysis through a CVC.

The primary endpoint of the study was time to CRBSI. The premise was that any time with a catheter is a risk and the use of DefenCath would significantly reduce the risk of CRBSI.  The DefenCath group showed a 71% reduction in CRBSI, meaning significantly fewer infections, hospitalizations, and deaths from serious infection.

Saurabh: The study found a 71% reduction in the risk of Catheter-Related Bloodstream Infections (CRBSIs) with DefenCath compared to heparin alone. Discuss its significance. 

Liz: CRBSIs kill 1 in 4 patients infected, presenting a severe risk to patients receiving hemodialysis via a CVC. The standard of care has been to lock catheters, meaning you fill the catheter in between dialysis sessions with either heparin, saline, or another liquid. The challenge with the currently available products like heparin, is that they are indicated to maintain catheter patency, but they don’t provide any protection to what is happening inside the catheter lumens. The lumens can be ripe with bacteria or fungi and once that starts multiplying, it can travel to the bloodstream, causing CRBSI.

DefenCath is unique in that it is not a treatment, but a novel, preventive product. The best way to treat an infection is to avoid one altogether. If it is approved, it will be the first and only antimicrobial catheter lock solution available to reduce the incidence of CRBSIs in patients with kidney failure receiving chronic hemodialysis through a CVC.

Saurabh: What is the importance of CorMedix's Phase 3 LOCK IT-100 study results being published in the Clinical Journal of the American Society of Nephrology (CJASN)? 

Liz: CJSAN is one of the leading nephrology journals, communicating the latest advances in nephrology research and care. We know the importance of ensuring nephrologists have the latest research to inform current and future practices. The publication of the Phase 3 LOCK-IT-100 study provides further insights into the efficacy and safety of DefenCath so nephrologists understand the potential impact it can have on reducing the high incidence of life-threatening CRBSIs in the hemodialysis community if approved.

Saurabh: Shed some light on the regulatory approvals and market designations for DefenCath and the additional marketing exclusivity that CorMedix expects to receive upon NDA approval for DefenCath. 

Liz: As mentioned earlier, DefenCath is an investigational product currently in review by the FDA. In 2015 DefenCath was designated by the FDA as a Qualified Infectious Disease Product (QIDP), and the original new drug application received priority review in recognition of its potential to address a critical unmet medical need.

If approved, we expect DefenCath will be eligible for 10.5 years of statutory marketing exclusivity in the U.S, which includes five years for New Chemical Entity designation, an additional extension of five years for QIDP designation, and six months upon completion of a pediatric hemodialysis clinical trial post-approval.

Saurabh: The company mentions that it is planning to conduct a clinical study in pediatric patients using a central venous catheter for hemodialysis upon the approval of NDA. Can you please provide us with more details such as expected study design, number of patients, sites, timeline and more? 

Liz: CorMedix has committed to conducting a clinical study in pediatric patients using a central venous catheter for hemodialysis. We are proud to take this project on as the vulnerabilities of dialyzing on a CVC are just as present for children. Over 50% of children over age 6 are dialyzed via a CVC and because children are prioritized for a transplant, keeping the CVC infection-free is mission-critical. Between 2010-2020, 13% of children with HD-CVC died of infection per the USRDS.

There are approximately 10,000 pediatric hemodialysis patients in the country, and we plan to partner with the pediatric specialists and renowned medical centers that treat them to conduct the most rigorous study and demonstrate the safety and efficacy of DefenCath in the pediatric population.

Saurabh: What are the other indications in which CorMedix plans to assess DefenCath?

Liz: Given its unique antimicrobial properties, we are excited to see where else we can take DefenCath.  There are other indications where the use of a CVC is even more prevalent than hemodialysis and, in those situations, the need to keep the line safe from infection is just as or more critical. For instance, 100% of patients receiving total parenteral nutrition or TPN are dependent on a CVC, and we’ve heard stories from clinicians that these patients can have multiple CVC replacements a year due to infection. We believe that the use of DefenCath in TPN patients and oncology patients receiving chemotherapy via a CVC will greatly improve their quality of life and finally provide clinicians with a tool to assist the already rigorous infection prevention techniques that are being employed.

DefenCath has the potential to change the way patients dependent on a CVC are managed and cared for if it becomes the standard of care. We are committed to exploring all of the avenues where DefenCath can make a difference.

Image Source: Canva

About the Author

Liz Hurlburt

Liz Hurlburt serves as our Executive Vice President of Clinical & Medical Affairs. Prior to that, she held several progressive management roles in clinical operations, most recently at Gemphire Therapeutics, as Vice President of Clinical Operations. Responsible for strategic and clinical development activities, Liz has a passion for growing and developing highly engaged teams and assuring the highest standards for medical affairs and clinical development execution. Liz received her B.A. in Leadership and Organizational Management from Bay Path College and a Master’s in Management and Leadership from Western Governors University.