FDA Authorizes Emergency Compassionate Use of VAR 200 for Ultra-Rare ApoCII Amyloidosis
Key Insights
The FDA has authorized emergency compassionate use of ZyVersa Therapeutics' VAR 200 for a patient with ApoCII amyloidosis (search), an ultra-rare kidney disease with no effective treatment options.
VAR 200, currently in Phase 2a trials for diabetic kidney disease (search), targets lipid accumulation in kidneys and was selected based on evidence of lipotoxic glomerular injury in the patient's kidney biopsy.
The treatment will be administered at the University of Miami under Dr. Alessia Fornoni's care, following the protocol of the ongoing diabetic kidney disease (search) clinical trial.
The FDA has authorized emergency compassionate use of ZyVersa Therapeutics' investigational drug VAR 200 for a patient with ApoCII amyloidosis (search), marking a significant development in the treatment of this ultra-rare kidney disease. The authorization provides access to the experimental therapy for a condition that currently has no effective treatment options.
ApoCII amyloidosis (search) results from abnormal organ deposition of toxic fibrillar amyloid proteins and is an ultra-rare condition that primarily affects the kidneys, manifesting with protein spillage into the urine (proteinuria) and chronic kidney disease (search). Despite treatment with standard-of-care renal drug therapy including ACE inhibitors, SGLT2 inhibitors, statins, and ezetimibe, the patient authorized to receive VAR 200 continues to show kidney disease progression.
Precision Medicine Approach Drives Treatment Selection
The decision to pursue emergency compassionate use was based on evidence from the patient's kidney biopsy, which demonstrated lipid deposition. Dr. Alessia Fornoni, Professor of Medicine at the University of Miami Miller School of Medicine and VAR 200 inventor, hypothesized that the drug has potential to alleviate lipid accumulation, proteinuria, and disease progression.
"We are at a time where Precision Medicine offers new tools to endophenotype patients and to identify the molecular signature that allows us to match the right patient to the right drug. The evidence of lipotoxic glomerular injury in this patient is what prompted me to request emergency compassionate use," stated Dr. Fornoni.
The rationale for VAR 200 use is supported by the drug's consistent results across preclinical studies in three different models of kidney disease, as well as supporting clinical data with 2-hydroxypropyl-beta-cyclodextrin (HP𝛽CD) in patients with lysosomal storage and protein deposition disorders, such as Niemann-Pick disease type C (search).
VAR 200 Mechanism and Clinical Development
VAR 200 (2-hydroxypropyl-beta-cyclodextrin, 2HP𝛽CD) is an injectable drug currently in Phase 2a development designed to ameliorate renal lipid accumulation that damages the kidneys' filtration system. The drug removes excess lipids from the kidney both passively and actively by upregulating cholesterol efflux transporters ABCA1 (search) and ABCG (search).
Preclinical studies with VAR 200 in animal models of focal segmental glomerulosclerosis (search) (FSGS), Alport syndrome (search), and diabetic kidney disease (search) have demonstrated reduced levels of cholesterol and lipids, protection against renal injury and fibrosis, and improvement in proteinuria.
The patient will receive treatment at the University of Miami Peggy and Harold Katz Family Drug Discovery Center under Dr. Fornoni's care. VAR 200 treatment and monitoring will follow the protocol of the ongoing diabetic kidney disease (search) clinical trial, VAR200-0301 (ClinicalTrials.Gov ID: NCT06489340).
Implications for Clinical Development
Stephen C. Glover, ZyVersa's Co-founder, Chairman, CEO, and President, expressed optimism about the potential impact: "We are proud to support Dr. Fornoni's Emergency Compassionate Use of VAR 200 in her patient with ApoCII amyloidosis (search) who currently has no other effective treatment options. We are hopeful that VAR 200 will help to improve the course of her disease and quality of life."
The company anticipates that data from this compassionate use case, combined with results from the Phase 2a diabetic kidney disease (search) trial, will inform the design of VAR 200's ongoing clinical development program. Dr. Fornoni noted that experimental treatment cases like this one could drive further clinical development for other patients as well.
Broader Development Strategy
VAR 200's lead indication is orphan kidney disease focal segmental glomerulosclerosis (search) (FSGS). Prior to initiating a Phase 2a trial in FSGS patients, ZyVersa is conducting a small Phase 2a trial in patients with diabetic kidney disease (search), which the company expects will provide patient proof-of-concept more quickly than an FSGS study. Alport Syndrome (search) and diabetic kidney disease indications may be pursued based on the company's indication expansion strategy.
Emergency Compassionate Use, also called Emergency Expanded Access, provides a pathway for patients with serious or immediately life-threatening diseases to gain access to investigational drugs for treatment outside of clinical trials when enrollment criteria are not met or there are no comparable or satisfactory alternative therapy options.