Vifor Pharma andAngion Biomedica Corp announced that the phase-III trial of Angion’s ANG-3777 did not demonstrate a statistically significant difference from placebo on the primary endpoint (eGFR at 12 months) in the population of deceased donor kidney transplant patients who were at risk for developing DGF.
ANG-3777 showed a modest but not statistically significant difference in eGFR of 53.3mL/min/1.73m2 versus 50.4mL/min/1.73m2 for placebo (2.9 mL/min/1.73m2 (p=0.33)). In addition, ANG-3777 demonstrated an inconsistent benefit on key secondary endpoints. Based upon these data, it is not expected there is sufficient evidence to support an indication in the studied DGF population.
The statistical analysis plan also included an analysis of only those people who completed the trial, without using a multiple imputation method to account for missing data and intercurrent events. Under this analysis, ANG-3777 showed a difference on 12 month eGFR of 57.1mL/min/1.73m2 versus 52.2mL/min/1.73m2 (4.9mL/min/1.73m2, p=0.06) for placebo. These data are potentially indicative of biologic activity of ANG-3777.
The overall safety profile of ANG-3777 in this trial was consistent with the overall experience in its clinical development program and consistent with the published literature in this patient population.
“Unfortunately, the results of the phase-III registrational trial did not confirm as strong of an effect as we hoped for in the interests of patients experiencing DGF after kidney transplantation”, said Dr. Klaus Henning Jensen, Chief Medical Officer of Vifor Pharma. “These kinds of challenges are part of clinical development activities. Our collaboration with Angion and the development of ANG-3777 in cardiac-surgery associated acute kidney injury (CSA-AKI) continues unchanged, with topline data expected later this year.”
“We are disappointed in the outcome of this trial. While we saw signals of activity for ANG‑3777, we hoped ANG-3777 would robustly demonstrate a benefit for transplant recipients who have no treatment options when their transplants have DGF,” stated Jay Venkatesan, M.D., Angion’s President and CEO. “The totality of the DGF data, together with the CSA-AKI data expected later this year, will inform our clinical strategy with respect to ANG-3777 going forward. I want to extend my special thanks to the patients, their families, and the investigators and their staff members who participated and worked diligently on this trial.”
This multi-center, double-blinded, and placebo-controlled phase-III trial randomized 253 patients 1:1 to receive ANG-3777 or a placebo treatment dosed once per day for three days. Eligible patients received a deceased donor transplant and were determined to be at risk for delayed graft function by having low urine output (oliguria) for more than 8 consecutive hours post-transplant, reflecting potential graft injury. Twenty-five transplant centers in the U.S. enrolled patients in this phase-III registration trial. The primary endpoint was renal function assessed by estimated glomerular filtration rate (eGFR) with a primary analysis time point of eGFR at twelve months using a pre-specified multiple imputation method.
