Gene Therapy for Wilson Disease Receives FDA Fast Track Designation


A phase 1/2 study evaluating Vivet Therapeutic’s VTX-801 is set to initiate in August 2021.

The FDA has granted fast track designation to Vivet Therapeutics’ VTX-801 for the treatment of Wilson disease.1

VTX-801 is an investigational, recombinant adeno-associated virus (rAAV) gene therapy designed to deliver a miniaturized, transgene encoding, ATP7B protein. The therapy is set to be investigated in the phase 1/2 GATEWAY trial (NCT04537377) starting in August 2021. 

“The FDA’s decision to grant VTX-801 Fast Track designation underscores the urgent need for new therapeutic options to address this devastating disease, which, if left untreated, can be fatal,” said Seng Cheng, PhD, senior vice president and chief scientific officer, Rare Disease Research Unit, Pfizer, which is partnered with Vivet, in a statement. “We are pleased to collaborate with Vivet on this important development program, which we believe, if successful, could make a meaningful difference in the lives of patients living with Wilson Disease.”

The multicenter, nonrandomized, open-label GATEWAY trial aims to evaluate the safety, tolerability, and pharmacological activity of VTX-801 delivered in a single intravenous infusion in adult patients with Wilson disease. The trial, which plans to enroll up to 16 patients, will be conducted across 6 centers in the US and Europe. 

READ MORE: FDA Lifts Clinical Hold on Novartis SMA Gene Therapy

Patients enrolled in GATEWAY will cease any background therapy treatments, participate in a predosing observational period, and be treated prophylactically with steroids. The trial’s primary end point will assess the safety and tolerability of up to 3 dose levels of VTX-801 at 52 weeks after infusion. Secondary end points will assess changes in radiocopper-related parameters as well as disease-related biomarkers such as free serum copper and serum ceruloplasmin activity. VTX-801 responder status will also be monitored to allow withdrawal in preference of standard-of-care.

Principal investigator Michael Schilsky, MD, director, Center of Excellence for Wilson Disease, Yale University, added to the statement that “we are proud to participate in this important clinical trial. If VTX-801 is successfully developed, it has the potential to be a truly innovative medicine with the ability to restore copper metabolism after a single injection, addressing significant unmet medical needs for patients with Wilson Disease.”

The ATP7B protein has previously been shown to restore copper homeostasis and reduce copper accumulation in mouse models of Wilson disease, as well as reverse liver disease.2 Research published in Hematology compared the AAV serotype 8 vector carrying the ATP7B complementary DNA (cDNA) to an optimized shorter AAV vector generated to be more efficient, which carried miniATP7B protein cDNA.

This therapy restored copper homeostasis in 6- and 12-week-old male and female mice with Wilson disease. The miniATP7B gene in combination with a synthetic AAV vector, AAVAnc80, was effective at preventing liver damage, restoring copper homeostasis, and improving survival 1 year after treatment. Transduction of approximately 20% of hepatocytes was sufficient to normalize copper homeostasis and the therapy did not result in copper deficiency.

“With the FDA’s authorization of the IND application for VTX-801–combined with Pfizer’s state-of-the-art gene therapy manufacturing capabilities–we are well-positioned to rapidly advance development of this potential therapy,” said Jean-Philippe Combal, PharmD, PhD, chief executive officer and co-founder of Vivet.1

1. VTX-801 receives U.S. FDA fast track designation for the treatment of Wilson Disease. News release. Vivet Therapeutics. August 12, 2021.
2. Murillo O, Moreno D, Gazquez C, et al. Liver expression of a MiniATP7B gene results in long-term restoration of copper homeostasis in a Wilson Disease model in mice. Hematology. 2019;70(1):108-126. doi:10.1002/hep.30535
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