ZyVersa Therapeutics Supports FDA-Authorized Emergency Compassionate Use of Cholesterol Efflux Mediator™ VAR 200 in a Patient with ApoCII Amyloidosis

Rhea-AI Summary

ZyVersa Therapeutics (NASDAQ:ZVSA) has received FDA authorization for Emergency Compassionate Use of its Cholesterol Efflux Mediator™ VAR 200 in a patient with ApoCII amyloidosis, an ultra-rare kidney condition. The treatment will be administered at the University of Miami under the care of Dr. Alessia Fornoni, who is also the inventor of VAR 200.

The patient, who has shown continued kidney disease progression despite standard treatments, will receive VAR 200 following the protocol of the ongoing Phase 2a diabetic kidney disease (DKD) clinical trial. The drug was selected due to evidence of lipid deposition in the patient's kidney biopsy and VAR 200's demonstrated ability to reduce renal lipid accumulation in preclinical studies.

Positive

• FDA authorization for Emergency Compassionate Use demonstrates regulatory flexibility
• Potential expansion of VAR 200's therapeutic applications beyond diabetic kidney disease
• Treatment supported by positive preclinical data in three different kidney disease models

Negative

• VAR 200 is still in early clinical development (Phase 2a)
• Success in a single compassionate use case may not predict broader efficacy

Insights

Biotech Investment Analyst

FDA-authorized compassionate use of VAR 200 validates ZyVersa's technology and potentially expands its market opportunities beyond DKD.

This FDA authorization for Emergency Compassionate Use represents a strategic opportunity for ZyVersa's clinical development program. The company's Cholesterol Efflux Mediator™ VAR 200, currently in Phase 2a trials for diabetic kidney disease, is now being deployed in a patient with ApoCII amyloidosis—an ultra-rare condition with limited treatment options.

This development carries several important implications:

• It demonstrates regulatory confidence in VAR 200's safety profile sufficient to permit compassionate use
• Provides ZyVersa an opportunity to gather early efficacy data in an additional indication beyond their primary DKD focus
• Potentially expands VAR 200's addressable market by establishing a mechanism-based approach rather than a disease-specific one
• Leverages VAR 200's unique ability to reduce lipid accumulation, which appears relevant across multiple kidney pathologies

The fact that treatment will be conducted under Dr. Fornoni, the drug's inventor, ensures optimal protocol implementation. This single-patient application could generate valuable data to inform future indication expansion strategy. For a clinical-stage biotech with a market cap below $50 million, every additional potential application significantly enhances the value proposition of their pipeline assets.

While a single compassionate use case won't materially impact financials near-term, positive outcomes could accelerate partnership discussions and enhance ZyVersa's strategic positioning in the kidney disease therapeutic landscape.

Nephrology Specialist

The application of VAR 200 for ApoCII amyloidosis represents a fascinating mechanistic approach to an ultra-rare kidney disease with few therapeutic options. What makes this case particularly intriguing is the precision medicine approach being employed.

The treating physician identified lipid deposition in the patient's kidney biopsy, creating a scientific rationale for VAR 200's application. This drug's mechanism—enhancing cholesterol efflux from tissues—directly addresses the lipotoxic injury pattern seen in this patient's kidneys.

From a nephrologist's perspective, the connection between ApoCII amyloidosis and VAR 200's mechanism is scientifically sound for several reasons:

• Amyloidoses involve abnormal protein deposition that disrupts tissue architecture and function
• Lipid accumulation often accompanies protein deposition disorders, creating a toxic cellular environment
• The patient's failure to respond to standard therapies (ACEi, SGLT2 inhibitors, statins, ezetimibe) suggests the need for a mechanism-specific approach
• VAR 200's hydroxypropyl-β-cyclodextrin (HPβCD) component has shown promise in other protein/lipid deposition disorders like Niemann-Pick disease

This case exemplifies translational medicine at its best—applying mechanistic insights from preclinical models directly to patient care. If successful, it could establish a precedent for targeting kidney diseases based on molecular phenotype rather than traditional diagnostic categories. The medical community will watch this case closely, as it may inspire similar mechanism-based approaches for other rare kidney diseases.

• ApoCII amyloidosis, resulting from abnormal organ deposition of toxic fibrillar amyloid proteins, is an ultra-rare condition that mostly affects the kidneys and manifests with protein spillage into the urine (proteinuria) and chronic kidney disease.
• Despite being treated with standard-of-care renal drug therapy (ACEi, SGLT2, statin, and ezetimibe), the patient authorized by FDA to receive VAR 200 is showing continued kidney disease progression. Because her kidney biopsy demonstrated lipid deposition, the treating physician, Dr. Alessia Fornoni, hypothesized that VAR 200 has potential to alleviate lipid accumulation, proteinuria, and disease progression. This is based on VAR 200’s consistent results across preclinical studies in three different models of kidney disease, and supporting HPβCD clinical data in patients with lysosomal storage and protein deposition disorders, such as Niemann-Pick disease type C.
• VAR 200, currently in a phase 2a clinical trial for diabetic kidney disease (DKD), was designed to passively and actively reduce renal lipid accumulation to protect against renal injury and fibrosis and improve kidney function.
  

WESTON, Fla., July 08, 2025 (GLOBE NEWSWIRE) -- ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA; “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of patients with renal and inflammatory diseases who have unmet medical needs, is pleased to provide regulatory and product support for FDA-authorized Emergency Compassionate Use of Cholesterol Efflux Mediator™ VAR 200 in a patient with ApoCII amyloidosis. Emergency Compassionate Use, also called Emergency Expanded Access, is a pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational drug for treatment outside of clinical trials when enrollment criteria are not met or there are no comparable or satisfactory alternative therapy options.

The patient with ApoCII amyloidosis will receive treatment at the University of Miami Peggy and Harold Katz Family Drug Discovery Center under the care of the Center Director, Dr. Alessia Fornoni, Professor of Medicine, University of Miami Miller School of Medicine, and VAR 200 inventor. VAR 200 treatment and monitoring will follow the protocol of the ongoing DKD clinical trial, VAR200-0301 (ClinicalTrials.Gov ID: NCT06489340).

“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. I am very excited about the opportunity to test the efficacy of VAR 200 for this new indication, as I believe experimental treatment cases like this one will drive further clinical development for other patients as well,” stated Dr. Fornoni.

“We are proud to support Dr. Fornoni’s Emergency Compassionate Use of VAR 200 in her patient with ApoCII amyloidosis 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,” said Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO, and President. “We look forward to learning the effects of VAR 200 on proteinuria in this patient with ApoCII amyloidosis, which in combination with the data from our Phase 2a DKD trial, will support the design of our ongoing VAR 200 clinical development program.”

ABOUT CHOLESTEROL EFFLUX MEDIATOR™ VAR 200

Cholesterol Efflux Mediator™ VAR 200 (2-hydroxypropyl-beta-cyclodextrin, 2HPβCD) is an injectable drug in phase 2 development to ameliorate renal lipid accumulation that damages the kidneys’ filtration system, leading to development and progression of kidney disease. VAR 200 removes excess lipids from the kidney both passively, and actively by upregulation of cholesterol efflux transporters, ABCA1 and ABCG.

Preclinical studies with VAR 200 in animal models of FSGS, Alport syndrome, and diabetic kidney disease demonstrate reduced levels of cholesterol and lipids, protection against renal injury and fibrosis, and improvement in proteinuria. Additional information can be found in the VAR 200 White Paper.

The lead indication for VAR 200 is orphan kidney disease, focal segmental glomerulosclerosis (FSGS). Prior to initiating a Phase 2a trial in patients with FSGS, we are conducting a small Phase 2a trial in patients with diabetic kidney disease, which we expect will provide patient proof-of-concept more quickly than an FSGS study. Alport Syndrome and diabetic kidney disease indications may be pursued based on our indication expansion strategy.

ABOUT ZYVERSA THERAPEUTICS, INC.

ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and peripheral inflammatory diseases. For more information, please visit www.zyversa.com. 

CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS

Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc. (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing.
New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities.

Corporate, IR, and Media Contact
Karen Cashmere
Chief Commercial Officer
kcashmere@zyversa.com 
786-251-9641
                

FAQ

What is the FDA Emergency Compassionate Use approval for ZVSA's VAR 200?

The FDA has authorized VAR 200's emergency use in a patient with ApoCII amyloidosis, a rare kidney condition, who has failed standard treatments and shows evidence of lipid deposition in kidney tissue.

What is ApoCII amyloidosis and how does VAR 200 aim to treat it?

ApoCII amyloidosis is an ultra-rare condition causing toxic protein deposits in organs, particularly kidneys. VAR 200 aims to reduce renal lipid accumulation to protect against kidney injury and improve function.

What stage of development is ZVSA's VAR 200 currently in?

VAR 200 is currently in a Phase 2a clinical trial for diabetic kidney disease (DKD), with the trial ID NCT06489340.

Who will oversee the compassionate use treatment of VAR 200?

Dr. Alessia Fornoni, the inventor of VAR 200 and Director of the University of Miami Peggy and Harold Katz Family Drug Discovery Center, will oversee the treatment.

How will the compassionate use results impact ZVSA's drug development?

The results will help understand VAR 200's effects on proteinuria in ApoCII amyloidosis and, combined with Phase 2a DKD trial data, will support the ongoing clinical development program.