Takeaways
- The FDA has granted Priority Review for pz-cel, an investigational gene-corrected epidermal sheet, as a treatment for recessive dystrophic epidermolysis bullosa (RDEB).
- The Prescription Drug User Fee Act (PDUFA) date is set for May 25, 2024, with no Advisory Committee meeting planned for pz-cel.
- The Biologics License Application (BLA) is supported by evidence from a phase 1/2 study and the pivotal phase 3 VITAL study, demonstrating wound healing and pain reduction in RDEB patients.
- RDEB is a rare connective tissue disorder caused by a defect in the COL7A1 gene, leading to the inability to produce functional Type VII collagen.
- Pz-cel aims to integrate the COL7A1 gene into the patient's skin cells using a retroviral vector, securing long-term expression and has received additional designations, including Regenerative Medicine Advanced Therapy and Orphan Drug.
The FDA has granted Priority Review for pz-cel (prademagene zamikeracel; Abeona), an investigational autologous, COL7A1 gene-corrected epidermal sheet to treat patients with recessive dystrophic epidermolysis bullosa (RDEB), Abeona Therapeutics announced in a press release.1
The FDA has set a Prescription Drug User Fee Act (PDUFA) date of May 25, 2024 and is not planning to have an Advisory Committee meeting to discuss pz-cel.1
The Biologics License Application (BLA) is supported by confirmatory evidence from a phase 1/2 study (NCT01263379) that enrolled 12 individuals aged 13 years and older and the pivotal phase 3 VITAL study (NCT04227106) that featured 11 participants aged 6 years and up.1-3
According to Abeona, both studies demonstrated that a 1-time application of pz-cel on “large and chronic” wounds revealed wound healing and pain reduction of RDEB, a rare connective tissue disorder characterized by skin wounds that result in pain and can lead to systemic complications.1
A defect in the COL7A1 gene leaves individuals unable to produce functioning Type VII collagen, which is necessary to anchor the dermal and epidermal layers of the skin.1
"In this Phase 3 trial with patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB), supported by Abeona and completed at Stanford University and the University of Massachusetts, investigators implanted sheets impregnated with the EB101 gene," Bernard A. Cohen, MD, professor of pediatrics and dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Contemporary Pediatrics.
"This turns on production of Collagen type VII and results in production of anchoring fibrils that attach the epidermis to dermis."
The treatment is designed to include the functional collagen-producing COL7A1 gene into the patient’s skin cells, enabling long-term expression via a retroviral vector to stably integrate into the dividing target cell genome.1
"The results of treated ulcers compared with control untreated ulcers were dramatic with healing of chronic wounds within 12 weeks and decrease in pain," Cohen added.
In addition to Priority Review designation, pz-cel has been granted Regenerative Medicine Advanced Therapy and Orphan Drug and Rare Pediatric Disease by the FDA.1
"Itching in treated wounds improved dramatically within 24 weeks, and the response to therapy was persistent," Cohen said. "The investigators have requested an early approval by FDA based on these Phase 3 study results. Hopefully we will hear from the FDA shortly."
References:
- Abeona Therapeutics announces FDA accepts and grants Priority Review for pz-cel Biologics License Application. Abeona Therapeutics. Press release. November 27, 2023. Accessed November 28, 2023. https://www.biopharmcatalyst.com/company/ABEO/news/171820
- Gene transfer for recessive dystrophic epidermolysis bullosa. ClincalTrials.gov. August 8, 2022. Accessed November 28, 2023. https://clinicaltrials.gov/study/NCT01263379
- Phase 3, open-label clinical trial of EB-101 for the treatment of recessive dystrophic epidermolysis bullosa (DEB). ClinicalTrials.gov. December 5, 2022. Accessed November 28, 2023. https://clinicaltrials.gov/study/NCT04227106
