FDA Approves DefenCath for Bloodstream Infections

CorMedix Inc. (Nasdaq: CRMD), a biopharmaceutical company focused on developing and commercializing therapeutic products for the prevention and treatment of life-threatening diseases and conditions, announced that the FDA has approved DefenCath® (taurolidine and heparin) catheter lock solution (CLS) to reduce the incidence of catheter-related bloodstream infections (CRBSIs) in a limited population of adult patients with kidney disease. In a Phase 3 clinical investigation, DefenCath, the first and only FDA-approved antimicrobial CLS in the United States, was proven to lower the incidence of CRBSIs by up to 71%.

“The approval of DefenCath marks a major advancement in reducing life-threatening infections for patients receiving hemodialysis via central venous catheters and an important milestone for CorMedix,” said Joseph Todisco, Chief Executive Officer of CorMedix. As the first FDA-approved antimicrobial catheter lock device developed to prevent CRBSIs, DefenCath provides healthcare practitioners with a way to lower infection risk in a patient population that is already vulnerable owing to underlying renal failure. We would like to thank all of the patients, caregivers, clinical investigators, and personnel who contributed to the development and regulatory approval of DefenCath. Our commercial team, along with the rest of our business, is preparing for commercial launch, and we look forward to collaborating with healthcare providers and facilities to bring DefenCath to hemodialysis patients in early 2024.”

The FDA approved DefenCath based on findings from the randomized, double-blind, active control, multicenter pivotal Phase 3 LOCK-IT-100 clinical trial, which was designed to evaluate DefenCath’s efficacy and safety in reducing the incidence of CRBSIs in patients with kidney failure receiving chronic hemodialysis. In the research, 806 people were randomly assigned to receive either DefenCath or heparin as a CLS. those in the DefenCath group experienced fewer CRBSI incidents than those in the control group. The Hazard Ratio was 0.29, equivalent to a 71% reduction in the probability of having a CRBSI. Based on demonstrable efficacy and a pre-specified level of statistical significance, an independent Data Safety and Monitoring Board recommended an early termination of the research with no safety concerns. The number of adverse events was comparable to the number of controls.

“Patients and their loved ones have faced many burdens related to kidney failure, including complications caused by catheter-related bloodstream infections and associated loss of work, severe disability, and death,” said Edward V. Hickey, III, President of the American Association of Kidney Patients and Chair of the Veterans Health Initiative. Until today, patients who required hemodialysis using a central venous catheter had little choice except to accept the considerable infection risks associated with the current standard of care. The FDA’s approval of DefenCath is a significant milestone for patients and their healthcare professionals since it provides a new option for reducing the dangers of CRBSIs.” Mr. Hickey is a kidney sufferer, a former senior member of the United States Congress, and a veteran of two presidential administrations.

Concerns Regarding Catheter-Related Bloodstream Infections

In patients with central venous catheters (CVCs), catheter-related bloodstream infections (CRBSIs) are frequent. A CVC will be placed for vascular access in around 80% of patients initiating hemodialysis. CRBSIs can occur in up to one-third of HD-CVC patients, with more than half occurring within the first three months of CVC installation. Every year, 250,000 CRBSIs occur in patients who have an intravascular device, such as a central venous catheter (CVC), with one in every four patients dying as a result. CRBSIs can result in more hospitalizations, longer hospital stays, and long-term consequences such cardiovascular events. A diverse variety of bacteria, many of which are antibiotic-resistant, cause CRBSIs in hemodialysis patients.

Catheter Lock Solution DefenCath® (taurolidine and heparin)

DefenCath is an antimicrobial catheter lock solution (CLS) approved by the FDA to prevent the occurrence of catheter-related bloodstream infections (CRBSIs) in a small cohort of adult renal failure patients receiving chronic hemodialysis via a central venous catheter (CVC). It is made up of the anticoagulant heparin and taurolidine, a non-antibiotic antibacterial and antifungal drug with a broad spectrum. DefenCath is intended to occupy the catheter lumen between dialysis sessions. Due to the chemical mode of action, microbial resistance to taurolidine has not been established in the laboratory or in clinical use in Europe.

DefenCath Indication and Important Safety Information

DefenCath was licensed under the 21st Century Cures Act’s limited population for antibacterial and antifungal medications (LPAD) pathway to meet unmet needs of patients with significant bacterial and fungal infections. Furthermore, the FDA designated DefenCath as a Qualified Infectious Disease Product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) Act, which encourages the development of antibacterial and antifungal medications that treat serious or life-threatening illnesses. The FDA approved DefenCath to minimize the risk of catheter-related bloodstream infections in adult kidney failure patients receiving continuous hemodialysis via a central venous catheter. It is approved for use in a small and select group of patients. DefenCath’s safety and effectiveness in populations other than adult patients with renal failure receiving chronic HD through a CVC have not been demonstrated.

DefenCath contains taurolidine, a thiadiazinane antibiotic, and heparin, an anticoagulant that can cause thrombocytopenia or HIT. It is contraindicated and should not be used in individuals who have known HIT or are allergic to taurolidine, heparin, or citrate. It is not designed to be used for system administration. Before starting the next hemodialysis session, DefenCath must be aspirated from the catheter and discarded.

The average age of patients in LOCK-IT-100 was 61 years, with 58% being male, 42% female, 63% white, and 30% black or African-American. Patients with diabetes accounted for 70% of patients at baseline, with a mean BMI of 30. The majority of patients had been on hemodialysis for less than a year. In 92% of cases, the CVC was found in the jugular vein.

Hemodialysis catheter malfunction, hemorrhage/bleeding, nausea, vomiting, dizziness, muscular chest discomfort, and thrombocytopenia were the most frequently reported adverse effects in 2% of LOCK-IT-100 patients utilizing DefenCath as a catheter lock solution. Adverse events resulting in mortality occurred in 5% (18/398) of DefenCath patients and 5% (21/399) of heparin patients. Adverse events resulting to study drug discontinuation occurred in 17% (69/398) of the DefenCath arm and 18% (72/399) of the heparin arm.

DefenCath’s safety and effectiveness in populations other than adult patients with renal failure receiving continuous hemodialysis through a CVC have not been demonstrated. Because DefenCath is not intended for systemic administration, maternal use is unlikely to result in fetal exposure, and breastfeeding is unlikely to result in infant exposure. There was no animal reproduction study with DefenCath. DefenCath’s safety and effectiveness in pediatric patients have not been established. There were no general differences in safety or effectiveness between patients 65 and younger and older adult patients.

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