Abeona Therapeutics Inc. has announced the resubmission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for prademagene zamikeracel (pz-cel), an investigational autologous cell-based gene therapy intended for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). This action follows a Type A meeting with the FDA in August 2024, where Abeona aligned with the agency on the content of the resubmission.
The resubmitted BLA aims to address all Chemistry, Manufacturing, and Controls (CMC) requirements outlined in the Complete Response Letter (CRL) received in April 2024. According to Abeona, the CRL did not identify any deficiencies related to the clinical efficacy or safety data, and the FDA did not request any new clinical trials or data to support the approval of pz-cel. The application is supported by data from the pivotal Phase 3 VIITAL™ study (NCT04227106) and a Phase 1/2a study (NCT01263379).
Addressing Manufacturing Requirements
The primary focus of the resubmission is to provide additional information to satisfy the CMC requirements specified by the FDA. This includes addressing observations from the completed Pre-License Inspection of Abeona's manufacturing facility. Vish Seshadri, Chief Executive Officer of Abeona, expressed confidence that the resubmission package adequately addresses these items.
Pz-cel: Gene Therapy for RDEB
Prademagene zamikeracel (pz-cel) is an autologous, COL7A1 gene therapy being developed for RDEB, a rare genetic skin disease caused by mutations in both copies of the COL7A1 gene. This genetic defect prevents cells from producing functional collagen VII protein, which is essential for forming anchoring fibrils that connect the epidermis to the dermis. The absence of these fibrils leads to fragile skin prone to blistering, chronic wounds, and an increased risk of infection and squamous cell carcinoma.
Pz-cel involves genetically correcting a patient's own skin cells with a functional COL7A1 gene, enabling them to produce collagen VII. These corrected cells are then expanded into keratinocyte sheets, which are surgically applied to cover wound areas in a single procedure. The FDA has granted pz-cel Regenerative Medicine Advanced Therapy, Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations.
Regulatory Timeline
Upon acceptance of the BLA resubmission, the FDA is expected to establish a new Prescription Drug User Fee Act (PDUFA) target action date for pz-cel. The review period for a resubmitted BLA is either two or six months from the resubmission date, depending on the FDA's classification of the resubmission as Class 1 or Class 2, respectively. The FDA typically decides whether to accept a BLA resubmission within 14 calendar days.
