One and done

DALLAS & WALTHAM, Mass.—Proteon Therapeutics is trying to make sure that a therapeutic treatment for those suffering from kidney disease ceases to be one that quite literally can leave patients with internal scars.

 

So what’s the situation? As Proteon notes, patients with severe chronic kidney disease (CKD) or end-stage renal disease require hemodialysis and need a high-flow vascular access to repeatedly connect the patient’s bloodstream to a hemodialysis machine for 12 hours per week.

 

Three times per week for three to four hours each session, blood is pumped from the body and passed through a dialysis machine that removes waste and excess water normally excreted by the kidneys. More than 2 million people worldwide, including more the 400,000 in the United States, require such treatment.

 

To achieve hemodialysis, surgeons create an arteriovenous fistula (AVF), connecting a vein to an artery, typically at the wrist or elbow, and resulting in a substantial increase in blood flow and vein dilation. A functioning AVF is a hemodialysis patient’s lifeline, enabling the patient to undergo life-sustaining hemodialysis.

 

“Sometimes the veins and arteries develop scars on the inside, narrowing the space for the blood to flow and requiring treatment to open the blockage,” explains Timothy Noyes, CEO of Proteon. “The fundamental challenge is maintaining blood flow where scarring has occurred. Our therapy, used once, prevents that scarring.”

 

Proteon, a company developing novel, first-in-class therapeutics to address the medical needs of patients with kidney and vascular diseases, announced positive results from a long-term analysis of more than three years of follow-up data from a Phase 2 study of its lead candidate, vonapanitase, in CKD patients undergoing surgical creation of a radiocephalic AVF for hemodialysis. The company, which has 12 employees, is enrolling patients in a Phase 3 multicenter, randomized, double-blind, placebo-controlled clinical study of vonapanitase.

 

The drug is administered once by a vascular surgeon immediately after the creation of an AVF, according to Noyes. In the Phase 2 multicenter, randomized, double-blind, placebo-controlled clinical study, patients who received vonapanitase reported adverse events related to the AVF comparable to placebo over the course of more than three years.

 

“Once scarring occurs and there is inadequate blood flow, the costs and morbidity are very high in these extremely sick patients,” he notes. “Our objective is to head off the cycle of interventions before the patient gets into them.”

 

Vonapanitase (formerly PRT-201), an investigational drug, has received Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration and Orphan Medicinal Product designation from the European Commission for hemodialysis vascular access indications. Vonapanitase may have multiple surgical and endovascular applications in which vessel injury leads to blockages in blood vessels and reduced blood flow, and it is currently being evaluated in a Phase 1 clinical trial in patients with symptomatic peripheral artery disease.

 

Data from the long-term analysis, presented at the National Kidney Foundation’s 2015 Spring Clinical Meetings in Dallas, demonstrated a trend of prolonged primary patency, the study’s primary endpoint, and a statistically significant improvement in the rate of corrective procedures, a secondary endpoint, over more than three years of follow-up for the 30 mcg vonapanitase dose as compared to placebo. An analysis of the results in the subset of patients receiving a radiocephalic AVF, which was not prespecified, showed statistically significant improvements in primary patency, secondary patency (AVF survival) and the rate of corrective procedures over more than three years of follow-up for the 30 mcg vonapanitase dose as compared to placebo.

 

“The Phase 2 results suggest that a single treatment of vonapanitase immediately after radiocephalic AVF surgical creation may yield durable benefits for patients,” according to Dr. Bradley Dixon, a nephrologist and associate professor of medicine at the University of Iowa’s department of internal medicine. “A radiocephalic AVF is the preferred form of vascular access for hemodialysis patients, and the benefits of vonapanitase, if observed in pivotal Phase 3 studies, would have great clinical importance to patients and their caregivers.”

 

“The results from more than three years of follow-up extend the positive findings we observed at one year in the non-prespecified subset analysis of patients undergoing surgical creation of radiocephalic AVFs—the same patient population we are studying in our ongoing Phase 3 clinical trial,” says Noyes. “This could have a dramatic and life-changing effect on patients with kidney failure.”