Aravive announced the company has begun enrolling patients in the Phase 2a clinical trial of AVB-500 in patients with kidney fibrosis, specifically IgA Nephropathy (IgAN).

"We are very pleased to initiate this first trial of AVB500 in patients with renal fibrosis," said Gail McIntyre Ph.D., DABT, CSO at Aravive. "GAS6 is more highly expressed in human IgAN tissues than normal kidney tissue, GAS6 levels correlate with severity of the disease and inhibition of the pathway preclinically has demonstrated a positive effect."

This is an open-label Phase 2a clinical study designed to evaluate the safety and efficacy of AVB500 in patients with biopsy-proven IgAN and excreting 1-3 grams of protein daily in their urine. The primary endpoints will be safety of AVB500 in the population and efficacy of AVB500 treatment on decreasing the amount of protein in the urine.

IgAN, also known as Berger's disease, is a kidney disease that occurs when an antibody called immunoglobulin A builds up in the kidneys. This results in local inflammation that, over time, damages the kidneys. Preclinical studies have demonstrated that GAS6 acts as a mitogen, stimulating mesangial cell proliferation through binding to its cell-surface receptor AXL and an AXL decoy protein can inhibit mesangial cell proliferation by interfering with the GAS6/AXL pathway. IgA nephropathy usually progresses slowly over years and patients can develop end-stage kidney failure, requiring dialysis. No cure exists for IgAN, but certain medications can slow its course.

AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity, both as a single agent and in combination with a variety of anticancer therapies including radiation therapy, immuno-oncology agents and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors is correlated to poor prognosis and survival, and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies.

Aravive reported positive data from the expansion cohort in the Phase 1b portion of a Phase 1b/2 clinical trial of AVB-500 in platinum-resistant recurrent ovarian cancer. AVB-500 continues to be well tolerated with no dose limiting toxicities. An investigator-sponsored Phase 1 study of AVB-500, in combination with durvalumab in patients with platinum-resistant recurrent epithelial ovarian cancer, is also ongoing. Based on AVB-500’s safety profile and specifically targeted mechanism of action, this drug candidate has the potential to be used both in combination with existing therapies, as well as a maintenance drug. The U.S. Food and Drug Administration granted Fast Track Designation to AVB-500 in platinum-resistant recurrent ovarian cancer.

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