The experimental treatment vonapanitase failed to improve a key barometer of unassisted blood flow in a Phase 3 study of patients with chronic kidney disease (CKD), according to its maker, Proteon Therapeutics.
But the treatment may improve another barometer of blood flow, the company said. It also may help improve unassisted or assisted use of a clogged fistula, or blood passageway, during dialysis, Proteon added.
The PATENCY-1 (NCT02414841) trial was designed to assess vonapanitase’s safety and effectiveness in 313 CKD patients receiving or expecting to receive dialysis. The research compared the results in a group that took vonapanitase versus a group that took a placebo.
Patients had to have surgery before their treatments to create a new access point to their bloodstream for dialysis. The access point, at the wrist, is called a radiocephalic arteriovenous fistula, or AVF.
Researchers hoped vonapanitase would improve primary unassisted patency. This was defined as blood flow from the time of AVF surgery until thrombosis — which is the development of a flow impediment — or until surgery to re-establish flow. The trial indicated that vonapanitase failed to improve primary unassisted patency.
The treatment appeared to improve secondary patency, however. This was defined as blood flow from the time an AVF was created until the time it was no longer used.
Proteon continues to recruit patients for the study, which has been conducted at 31 US medical centers. Patients were followed for up to a year after joining the Phase 3 part of the study.
The risk that a patient would lose primary unassisted patency was 17% lower among vonapanitase users than placebo users, said the researchers, who had hoped to find a larger difference. At one year of follow-up, 42% of vonapanitase users had preserved primary unassisted patency, versus 31% of placebo users.
Vonapanitase users had a 34% lower risk of secondary patency loss compared with placebo users. At the end of a year, 74% of patients on vonapanitase had preserved secondary patency, compared with 61% of placebo users.
Another finding was that 39.2% of patients treated with vonapanitase achieved assisted use of their fistula for dialysis, versus 25% treated with a placebo. In addition, 63.9% of patients treated with vonapanitase were able to use their fistula for dialysis either unassisted or assisted, versus 44.4% of patients treated with a placebo.
In addition, 62.9% of those on vonapanitase achieved a key measure of blood flow known as unassisted maturation, versus 53.4% of placebo users. The hallmarks of unassisted maturation are a vein diameter of at least 4 millimeters and a blood flow of at least 500 milliliters per minute for three months without loss of primary patency.
Over one year, patients treated with vonapanitase had an average of 1.10 surgical procedures — including thrombectomies, angioplasties, and stent deployments — compared with 1.48 for the placebos.
|“We are disappointed that the study missed the primary endpoint (improved primary unassisted patency),” Steven Burke, MD, senior vice president and chief medical officer of Proteon Therapeutics, said in a press release. “However, it appears that vonapanitase had a drug effect and we are encouraged by the secondary patency and fistula use for hemodialysis findings in this trial, both of which we believe are clinically important.”|