ZyVersa Therapeutics has reached a significant milestone in its development of VAR 200, announcing the activation of its first clinical site for a Phase 2a trial targeting diabetic kidney disease (DKD). The Clinical Advancement Center in San Antonio, Texas, led by principal investigator Pablo Pergola, MD, PhD, is now ready to begin patient recruitment for this first-in-human study of the potential first-in-class treatment.
Addressing an Unmet Medical Need
VAR 200 represents a novel approach to treating kidney disease by targeting renal lipotoxicity, a pathogenic pathway that has been largely neglected in current therapeutic strategies. According to ZyVersa, there are currently no available drugs targeting renal lipotoxicity, which damages the kidneys' filtration system and causes protein leakage into the urine (proteinuria) and disease progression.
"There is a large body of evidence demonstrating the critical need for therapies to address kidney lipotoxicity, a key pathway in development and progression of DKD and other kidney diseases," said Stephen C. Glover, ZyVersa's Co-founder, Chairman, CEO, and President. The company's approach targets excess accumulation of cholesterol and lipids in the glomerulus, the main filtering unit of the kidney.
Clinical Trial Design and Timeline
The Phase 2a proof-of-concept study is designed as a 16-week open-label trial, consisting of 12 weeks of treatment followed by a four-week follow-up period. The study will be conducted at one to two US sites and will enroll an adequate number of subjects to complete eight patients with type 2 diabetes and diabetic kidney disease with proteinuria.
VAR 200 will be administered intravenously twice weekly at a single dose and will be added to each patient's stable drug regimen. The primary efficacy endpoint is the percent change from baseline to week 12 in urinary albumin to creatinine ratio, a key marker of kidney function and disease progression.
ZyVersa expects preliminary data in the second half of 2025, with final results anticipated in the second half of 2026.
Mechanism of Action and Preclinical Evidence
VAR 200, also known as 2-hydroxypropyl-beta-cyclodextrin (2HPβCD), functions as a Cholesterol Efflux Mediator™. The injectable drug works to ameliorate renal lipid accumulation through both passive and active mechanisms, including upregulation of cholesterol efflux transporters ABCA1 and ABCG.
Preclinical studies have demonstrated VAR 200's efficacy across multiple kidney disease models, including DKD, Focal Segmental Glomerulosclerosis (FSGS), and Alport Syndrome. These studies showed reduced levels of cholesterol and lipids, protection against renal injury and fibrosis, and improvement in proteinuria.
Market Context and Development Strategy
The clinical need for new kidney disease treatments remains substantial. According to ZyVersa, despite newer treatment options for kidney disease, over 130,000 patients progress to renal failure each year in the US, and more than 800,000 patients are living with renal failure requiring dialysis or transplant to sustain life.
The company believes that adding VAR 200 to standard-of-care drugs, such as ACE inhibitors, ARBs, and SGLT2 inhibitors that address other pathogenic pathways, could be disease-modifying and provide better protection against further kidney injury and disease progression.
While VAR 200's lead indication is the orphan kidney disease FSGS, ZyVersa is conducting the DKD trial first, expecting it will provide patient proof-of-concept more quickly than an FSGS study. The company may pursue Alport Syndrome and diabetic kidney disease indications based on its indication expansion strategy.
Company Profile
ZyVersa Therapeutics is a clinical-stage specialty biopharmaceutical company developing first-in-class drugs for patients with renal and inflammatory diseases. The company's therapeutic pipeline is built around two proprietary technologies: Cholesterol Efflux Mediator™ VAR 200 for kidney diseases and Inflammasome ASC Inhibitor IC 100 for CNS and peripheral inflammatory diseases.
