Cylerus is developing innovative new methods of drug delivery for prosthetic vascular grafts for dialysis access to improve the outcomes for patients.
Cylerus, an innovative drug delivery systems company based in the United States has developed a novel medical device. The device is intended to improve the patency and longevity of prosthetic vascular grafts for patients with end-stage renal disease who need haemodialysis. Cylerus expects the device to improve quality of life and treatment outcomes with end-stage renal disease.
Why are prosthetic vascular grafts used?
Prosthetic vascular grafts are needed for patients with end-stage renal disease (ERSD). Patients with ERSD must undergo haemodialysis, which is the filtering of the blood to remove toxins and waste productions, two to three times per week. During dialysis, a dialysis and the special filter, an artificial kidney, filter the blood. This happens in place of the diseased kidneys of the patient which are no longer able to function effectively. Before routine dialysis occurs, the patient has a minor surgical procedure to establish vascular access, allowing the dialyser to connect to the patient’s circulation.
There are a limited number of options available to create vascular access to the patient. Establishing chronic vascular access is done most commonly using a fistula, joining an artery and a vein in the lower or upper arm of the patient. However, this method can only be used for patients with healthy veins and it sometimes takes months for arteriovenous fistulas (AVFs) to mature. Approximately half of the AVFs fail to sustain effective haemodialysis.
Another option for chronic vascular access is a prosthetic vascular graft. Prosthetic vascular grafts are an attractive option because they can be used for dialysis much sooner than an AVF. However, they are costly, and they remain a source of morbidity and hospitalisation for dialysis patients. The common problems associated with them are thrombosis and stenosis in the outflow tract causing graft failure, infection, and low blood flow. A long-term patency is required to improve patient outcomes and reduce the healthcare costs.
Prosthetic vascular grafts often become blocked due to stenosis, a type of obstruction. Frequently, the proliferation of cells in the blood vessel and the formation of excess scar tissue which obstructs blood flow is responsible for causing stenosis.
How is Cylerus revolutionising vascular drug delivery?
Cylerus is extending the utility and function of prosthetic vascular grafts and has developed a novel medical device, a local drug delivery system, called the Drug-Eluting Cuff (DEC). The DEC graft has a pre-emptive focus and aims to account for the possibility of stenosis before it occurs, rather than as a reactionary strategy.
It significantly increases the lifetime of the critical access sites, the prosthetic vascular grafts, while decreasing the costs and the harmful consequences to patients caused by repeated interventions to maintain graft patency to support life-sustaining haemodialysis.
Cylerus’ ePTFE Drug Eluting Cuff (DEC) graft local drug delivery system efficiently targets a stable formulated, known drug (sirolimus) to sites of stenosis. A mini-osmotic pump continuously delivers sirolimus to the cuff upstream from the graft anastomosis, and the sirolimus prevents neointimal hyperplasia.
The advantages of local drug delivery include:
- Controlled continuous delivery of sirolimus through porous ePTFE;
- Sirolimus formulation is stable at body temperature;
- Infusion can be adjusted, delayed, or stopped;
- Systemic drug concentrations of sirolimus well below immunosuppressive levels;
- Adventitial healing is unaffected; and
- The ready antidote to stop or remove the drug pump leaving a largely unaffected ePTFE graft.
The market need for prosthetic vascular grafts
Currently, there are over one million patients worldwide who require multi-weekly sessions of dialysis, over 400,000 of which are in the USA.
The following statistics indicate the prevalence of haemodialysis treatments and patients diagnosed with Peripheral Vascular Disease:
- In 2015 there were 703,243 dialysis and transplant patients receiving ESRD treatment1
- 125,000 patients with ePTFE grafts that require ~200,000 interventions per year (1.6 interventions/yr.)
- 1bn/year (~€0.89bn) in placing/maintaining haemodialysis access
- Approximately 8.5 million people in the USA have Peripheral Vascular Disease (PVD)
- Over 500,000 patients are estimated to undergo multi-weekly dialysis in the United States by 2020.
Moving on to clinical development
Cylerus is based in Melbourne, Florida, and specialises in vascular drug delivery innovations. Cylerus specialises in vascular drug delivery innovations. Their DEC that can be combined with an implantable drug pump and the FDA approved drug, sirolimus.
The DEC is a product of years of research originating in Dr Stephen R Hanson (founder and board chairman of Cylerus)’s laboratory at Emory University in Atlanta, GA and then at Oregon Health & Science University (OHSU) in Portland, OR.
Dr Ronald J Shebuski, Sr, the President and CEO of Cylerus, leads the research and development of a formation of sirolimus which is biocompatible with the DEC, catheter delivery tubing and drug pump and oversees the preclinical safety and efficacy studies of the DEC sirolimus combination.
Dr Ronald Shebuski, the president and CEO of Cylerus, Inc, explained: “Following successful completion of Phase II of the current SBIR Fast Track Grant awarded Cylerus by the National Institute of Aging (NIA), the company will move into clinical development. The Phase II SBIR will fund FDA-required preclinical safety work at the University of Arizona-Tucson, which is a key collaborator to Cylerus on this project.”
The goal for Cylerus is to extend how long prosthetic vascular access grafts can be successfully used for haemodialysis. Their drug delivery technology could significantly decrease the morbidity associated with the maintenance of synthetic grafts, improve the quality of life for patients, and reduce high healthcare costs.
1 2017 USRDS Annual Data Report | Volume 2 – ESRD in the United States