Kidney Disease Trial Fails: What PATENCY-2 Means for CKD Research
A closely watched Phase III clinical trial evaluating a promising treatment for kidney disease has failed to meet its primary endpoints, raising important questions about the path forward for hemodialysis vascular access research. Proteon Therapeutics announced that its PATENCY-2 trial of vonapanitase in patients with chronic kidney disease (CKD) did not achieve statistically significant results on either of its co-primary endpoints, despite earlier signals of potential benefit in prior studies.
For the clinical research community, failed trials are not the end of the story. They represent critical data points that reshape how sponsors, investigators, and regulators think about trial design, patient selection, and endpoint strategy in complex therapeutic areas like nephrology.
What Is Chronic Kidney Disease and Why Does Hemodialysis Access Matter?
Chronic kidney disease is a progressive condition in which the kidneys gradually lose their ability to filter waste and excess fluids from the blood. As kidney disease advances to end stage renal disease, patients typically require hemodialysis, a process that filters the blood through a machine several times per week.
Hemodialysis depends on reliable vascular access, and the most preferred form is an arteriovenous fistula, a surgically created connection between an artery and a vein in the arm. However, fistula failure rates remain unacceptably high. As Anthony J. Bleyer, professor of Nephrology at Wake Forest Baptist Health and lead author of a related study, noted: “While a functioning arteriovenous fistula remains the gold standard for hemodialysis vascular access, failure rates remain unacceptably high, resulting in increased morbidity and mortality in patients with kidney disease and higher health care costs.”
This unmet need is precisely what vonapanitase was designed to address.
About Vonapanitase and the PATENCY-2 Trial
Vonapanitase is a recombinant human elastase designed to improve hemodialysis vascular access outcomes with a single administration at the time of fistula creation. The drug had received Breakthrough Therapy, Fast Track, and Orphan Drug designations from the FDA, as well as Orphan Medicinal Product designation from the European Commission, reflecting the significant unmet need in this area of kidney disease treatment.
The PATENCY-2 trial enrolled 603 patients across 39 medical centers in the United States and Canada. It was the fourth trial in Proteon’s clinical program for vonapanitase, and patients in each trial were followed for up to one year with an additional two years of extended follow-up. Across all four trials, Proteon enrolled more than 1,100 patients at more than 60 centers, representing one of the largest clinical development programs ever conducted in hemodialysis vascular access.
The trial had two co-primary endpoints: fistula used for hemodialysis, and secondary patency, which measures how long a fistula remains functional before final failure.
Why the Trial Failed to Meet Its Endpoints
On the first co-primary endpoint, 69.7 percent of patients treated with vonapanitase achieved fistula use for hemodialysis, compared to 65.1 percent of placebo patients. While numerically higher in the treatment group, this difference did not reach statistical significance.
On the second co-primary endpoint, secondary patency, a comparison of Kaplan-Meier curves showed no statistically significant difference between groups. At one year, 78 percent of kidney disease patients receiving vonapanitase maintained secondary patency compared to 76 percent of placebo patients.
“We believe this trial was well conducted and are surprised and disappointed by these results,” said Timothy Noyes, president and CEO of Proteon Therapeutics. “We want to thank the clinical investigators and patients who volunteered to participate in this important clinical program.”
Context: PATENCY-1 Also Fell Short
The PATENCY-2 failure was not entirely unexpected in light of the earlier PATENCY-1 trial, which also failed to meet its primary endpoint of improved primary unassisted patency. Results from PATENCY-1 were announced in December 2016, with data published in the Journal of Vascular Surgery in January 2019.
However, PATENCY-1 did show a pre-specified secondary endpoint result: a 34 percent decrease in the risk of secondary patency loss over one year compared to placebo, and a 45 percent relative increase in fistula use for hemodialysis compared to placebo. These secondary findings fueled optimism for PATENCY-2, making the failure of the larger confirmatory trial especially difficult for the company and the field.
Following the PATENCY-2 announcement, Proteon shares fell 84 percent. The company reported approximately 16.5 million dollars in cash and available investments as of March 31, 2019, and stated it would evaluate its strategic options after reviewing the full PATENCY-2 dataset.
What Failed Trials Teach the Clinical Research Community
Negative trial results in kidney disease research carry significant scientific value. Understanding why a well designed, adequately powered trial fails to meet its endpoints, despite biologically plausible mechanisms and prior positive signals, is essential to advancing the field.
Key questions that arise from the PATENCY-2 results include whether the endpoint definitions adequately captured meaningful clinical benefit, whether patient selection criteria were optimally specified, and whether the single administration design was the right approach given the complexity of kidney disease progression.
These are exactly the kinds of questions that experienced clinical research organizations must help sponsors think through when designing nephrology trials.
FOMAT and Nephrology Clinical Research
FOMAT Medical Research has experience supporting clinical trials in nephrology and related therapeutic areas. Our national network of community-based investigators includes sites with access to kidney disease patient populations, including those requiring hemodialysis and vascular access interventions. We support sponsors and CROs in designing and executing Phase I through Phase IV studies with the operational rigor and patient diversity that complex nephrology trials demand.
If you are a Sponsor or CRO working in kidney disease or related areas, contact our team to learn how FOMAT can support your next study.