The US Food and Drug Administration (FDA) on Wednesday issued new draft guidance detailing its expectations for drugs intended to treat delayed graft function (DGF) in kidney transplant patients.
DGF is a condition that involves suboptimal kidney function immediately following a kidney transplantation, and is usually defined as the need for dialysis within seven days of receiving a transplant, though FDA notes there are other accepted definitions for the condition.
There are currently no drugs approved to prevent DGF, and FDA says that "no standard of care has been demonstrated to be effective" at preventing the condition.
"The main reason to prevent DGF is to avoid the need for dialysis. Dialysis is a choice of last resort and puts the graft at risk because of potential hypotension, risk of thrombosis, increase in hospitalization, and worse clinical outcome, as reported in various publications," FDA writes.
FDA also notes that DGF has been reported to negatively impact several long-term patient outcomes, including graft survival, acute rejection and renal function, but notes that it remains to be seen whether preventing DGF will lead to longer patient or graft survival.
FDA says it intends for its draft guidance to serve as a point of discussion between its Division of Transplant and Ophthalmology Products, drugmakers and academia.
The agency also says that the guidance does not address the treatment of DGF or improving graft quality, but notes that those issues may be covered in future guidance.
According FDA, sponsors should conduct two randomized placebo-controlled Phase III superiority studies to demonstrate effectiveness if the drug they are testing isn't approved for any other indications, though the agency says that a single Phase III study in combination with other evidence study may be sufficient if the drug has already gone through trials in a closely related indication or if the results of efficacy in a single trial are "highly robust."
FDA also says the study protocol should specify the type of donors (i.e., donation after brain death, donor after cardiac death or living donor) that will be used, as well as the type of organ recovery, storage, transport conditions and post-transplantation immunosuppressive therapy.
In addition, FDA says that sponsors should plan on building a preapproval safety database of at least 300 patients, but says that a smaller database may be appropriate "depending on the benefit demonstrated."
The draft guidance goes on to make specific recommendations for primary and secondary endpoint selection, safety considerations, statistical analysis and specifies when sponsors should submit applications to be considered for accelerated approval.