A pivotal phase 3 study of vonapanitase (Proteon Therapeutics), an investigational drug intended to improve arteriovenous fistula patency, did not meet its primary endpoint of improved primary unassisted patency compared with placebo (P = 0.254). However, the results for the trial’s secondary endpoint suggested that vonapanitase may improve secondary patency compared with placebo (P = 0.048). Moreover, data from one of the trial’s three tertiary endpoints suggested that vonapanitase may improve unassisted fistula use for hemodialysis (P = 0.035) and any use of the fistula (unassisted or assisted) for hemodialysis (P = 0.006).
The PATENCY-1 trial evaluated the safety and efficacy of a single dose of vonapanitase in patients with chronic kidney disease (CKD) receiving or expecting to receive hemodialysis who underwent surgical creation of a radiocephalic arteriovenous fistula. The multicenter, randomized, double-blind, placebo-controlled study involved 209 vonapanitase-treated patients and 102 placebo-treated patients.
The study’s primary endpoint––primary unassisted patency––is the length of time from the surgical creation of a fistula to the first occurrence of a fistula thrombosis or corrective procedure to restore or maintain patency (blood flow). In the PATENCY-1 trial, vonapanitase-treated patients showed a 17% reduction in the risk of primary unassisted patency loss during one year compared with placebo (P = 0.254). At the end of one year, 42% of the patients who received vonapanitase retained primary unassisted patency compared with 31% of placebo-treated patients.
The study’s secondary endpoint––secondary patency––is the length of time from surgical creation until fistula abandonment (final failure). In the PATENCY-1 trial, vonapanitase-treated patients had a 34% reduction in the risk of secondary patency loss during one year compared with placebo (P = 0.048). At the end of one year, 74% of vonapanitase-treated patients maintained secondary patency compared with 61% of placebo-treated patients.
The proportions of patients reporting adverse events (AEs) were comparable between the vonapanitase and placebo arms. The most common AEs were consistent with medical events experienced by CKD patients undergoing radiocephalic fistula surgery. The AEs included vascular stenosis (38.3% for vonapanitase versus 40.2% for placebo); fistula thrombosis (19.6% vs. 26.5%); numbness (5.3% vs. 4.9%); and procedural pain (4.8% vs. 5.9%).
Vonapanitase has received fast track and orphan drug designations from the FDA for hemodialysis vascular-access indications.
Source: Proteon Therapeutics; December 13, 2016.