Dr. Anthony Bleyer is Professor of Internal Medicine and Nephrology at Wake Forest School of Medicine. He discusses his SCM17 late-breaking abstract, The Effect of Topically Applied Vonapanitase on Fistula Outcomes: Results of the PATENCY-1 Trial, with Nathaniel Reisinger (@nephrothaniel), AJKDBlog Guest Contributor.
AJKDBlog: What would you like to tell AJKDBlog about your poster?
Dr. Bleyer: It’s a trial of topically applied vonapanitase to promote radiocephalic fistula patency and use for dialysis. Vonapanitase is an elastase, an enzyme that breaks up elastase into smaller fragments. This was studied first in basic science laboratories and then in a phase 1 and phase 2 study. It showed promise as a drug that, when applied topically at the time of surgery, could help to prevent stenosis and improve fistula patency. We were involved in a multi-center double-blind placebo-controlled trial of 313 patients at 31 US centers and the primary outcome was primary patency, which is the time from fistula surgical creation until the time it first thromboses or until it requires a procedure to restore or maintain patency.
The surgeons, after joining together the vein and the artery, at the time of the operation, apply vonapanitase to the anastamosis for 10 minutes. It’s not a drug that patients have to take. It’s not given at the dialysis unit. It’s just applied one time at the time of surgery. The primary endpoint for the study was to see if primary patency was observed. Our results show that 42% of the patients in the vonapanitase group did not require a procedure or did not thrombose, whereas in the placebo group, only 31% did not require a procedure or did not thrombose. The difference was not statistically significant, however, the p value was 0.254.
Then, we looked at our secondary outcome. Secondary patency is defined as the time from the fistula creation until the fistula thromboses or is abandoned. So the patients can have had procedures, but as long as it stays patent, it is considered secondarily patent. In this endpoint, 74% of the vonapanitase group did not thrombose or were not abandoned, whereas only 61% of the placebo group did not thrombose or were not abandoned. This was statistically significant at a p value of 0.048. There was a hazard ratio of 0.66.
In the tertiary endpoint, 64% of the fistulas that had vonapanitase applied were able to be used for dialysis, whereas only 44% of the fistulas that were in the placebo group were used. Though the study did not meet it’s primary endpoint, there was a lot of evidence to support that this drug is clinically relevant. Actually, the secondary endpoint and the use for hemodialysis might be even more important clinically than primary patency. Now there’s another phase 3 trial going on that’s looking at secondary patency as one of the primary endpoints. It’s a very interesting drug even though it didn’t make its primary endpoint. I personally think it’s very promising.
AJKDBlog: How does the drug actually work?
Dr. Bleyer: It cleaves protein bonds in the protein elastin. Elastin is found in the blood vessel wall. It’s thought, based on several experiments, that these elastin fragments are chemoattractants and they prevent cells from migrating into the intima of the vessel and prevent cellular migration and stenosis.
AJKDBlog: How do you see this drug being used clinically?
Dr. Bleyer: I think if it meets its primary endpoint in the next trial, I can see that it would be used on most fistulas. A weakness of this study is that we only looked at radiocephalic fistulas. For radiocephalic fistulas, it looks like it could be a good drug in the future and potentially other studies could find it useful in other fistulas.
AJKDBlog: When should we expect the results of the next phase?
Dr. Bleyer: Probably in another year.
AJKDblog: Do you have anything else to add?
Dr. Bleyer: I think it’s really exciting. I think we all know that the fistula is a lifeline for dialysis and I really like the idea that it’s just topically applied in the operating room. There are no problems with compliance. Patients don’t have to take it over and over again. It’s applied topically so we showed no adverse events. It’s very well-tolerated.
AJKDBlog: Thanks a lot! We really appreciate this interview.
Dr. Bleyer: Thank you.