Jonathan S. Bromberg
Use of the hepatocyte growth factor mimetic ANG-3777 showed long-term improvement in kidney function in patients who underwent transplantation but had signs of possible kidney injury after transplant.
“The two leading contributors to early graft failure are acute rejection and acute kidney injury (AKI) occurring during the transplantation process. While rejection can be managed utilizing immunosuppressant therapy, no therapies currently exist for [delayed graft function] DGF-associated AKI,” Jonathan S. Bromberg, MD, PhD, professor of surgery and microbiology and immunology and vice chair for research at the University of Maryland, and colleagues wrote.
They noted 20% to 50% of renal transplantation patients experience AKI. Currently, main management strategies are dialysis and monitoring for rejection with serial biopsies.
“DGF is associated with increased medical costs, including longer hospital stays, more frequent out-patient visits, increased imaging, increased invasive procedures including dialysis, and pharmacologic therapies,” the authors wrote.
Donor injury, length of cold ischemia time and ischemia reperfusion injury were significantly higher in organs procured from deceased compared to living donors and are leading factors that contribute to DGF-associated AKI, they said.
Patients selected for the phase 2 study of ANG-3777 had urine output of less than 50 cc/hour for 8 consecutive hours during the first 24 hours post-transplantation. Nineteen patients received once-daily IV infusions of ANG-3777 (2 mg/kg) and nine patients received placebo. The primary endpoint was days needed to achieve greater than 1,200 cc of urine output for 24 hours.
Results showed patients treated with ANG-3777 were more likely to achieve the primary endpoint by 28 days post-transplantation (78.9% vs 44.4%).
“Compared to placebo, patients in the ANG-3777 arm had larger increases in urine output; lower [serum creatinine] SCr; greater reduction in C-reactive protein (CRP) and neutrophil gelatinase-associated lipocalin (NGAL); fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher eGFR,” the authors wrote. “There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile.”
The authors said while adverse events were seen in a similar percentage of patients in both study arms, events per subject were twice as high in the placebo arm.
“We believe the publication of the phase 2 data in Transplantation further validates ANG-3777 as a potential treatment for acute organ injuries ... our enthusiasm around this program is supported by these phase 2 results showing ANG-3777 was generally well-tolerated and led to clinically meaningful improvements as compared to placebo in several key endpoints, including eGFR,” Jay Venkatesan, MD, Angion Biomedica Corp. president and CEO, said in a company press release.
“Our findings provide further support ANG-3777 has the potential to represent a significant improvement over current standard of care for patients in need of an effective therapeutic option,” Bromberg said in the release. – by Mark E. Neumann
Disclosures: Funding for this research was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, grant #DK066654. Bromberg reports research funding and/or consultancy fees unrelated to this study from Angion Biomedica. Please see the study for all other authors’ relevant financial disclosures.