FDA Tells Abeona It Won’t Approve RDEB Cell Therapy without Additional CMC Information

Rare Daily Staff

The U.S. Food and Drug Administration told Abeona Therapeutics that it would not approve its experimental cell therapy prademagene zamikeracel for the rare connective tissue disorder recessive dystrophic epidermolysis bullosa without additional information to satisfy the agency’s chemistry, manufacturing, and controls requirements.

The FDA provided Abeona with a Complete Response Letter following its completion of Abeona’s Late Cycle Review Meeting with the agency in March 2024. The company said it submitted plans to the FDA with the commitment to provide chemistry, manufacturing, and controls (CMC) data prior to approval of its application and full validation reports after approval in mid-2024. The FDA indicated that the proposed timing of the data submission by Abeona would not allow sufficient time for the FDA to complete its review on its original timeline of May 25, 2024.

The information needed to satisfy the CMC requests in the complete response letter relates to validation requirements for certain manufacturing and release testing methods, including some that were captured in the observations during the FDA’s pre-license inspection. The letter did not identify any deficiencies related to the clinical efficacy or clinical safety data in the company’s application, and the FDA did not request any new clinical trials or clinical data to support the approval of prademagene zamikeracel (pz-cel).

“While we are surprised and disappointed by this CRL, we are committed to providing the CMC information necessary to respond to the agency’s asks, with the goal of bringing pz-cel to patients with recessive dystrophic epidermolysis bullosa (RDEB) as quickly as possible,” said Vish Seshadri, CEO of Abeona. “We are already hard at work generating the additional CMC information, and we expect that all of FDA’s requests will be addressable in a reasonable timeframe. We anticipate completing the BLA resubmission in the third quarter of 2024 with necessary updates to fully satisfy all the deficiencies outlined in the CRL.”

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by a defect in the COL7A1 gene that results in the inability to produce Type VII collagen. Pz-cel, Abeona’s experimental autologous, COL7A1 gene-corrected epidermal sheets, is currently being developed for the treatment RDEB.

Pz-cel is designed to incorporate the functional collagen-producing COL7A1 gene into a patient’s own skin cells and enable long-term gene expression by using a retroviral vector to stably integrate into the dividing target cell genome. Pz-cel is being investigated for its ability to enable normal Type VII collagen expression and to facilitate wound healing and pain reduction in even the toughest-to-treat RDEB wounds after a one-time application procedure.

The pivotal phase 3 VIITAL study is a randomized clinical trial that evaluated the efficacy, safety and tolerability of pz-cel in 43 large chronic wound pairs in 11 subjects with RDEB. The FDA has granted pz-cel Regenerative Medicine Advanced Therapy, Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations.

Photo: Vish Seshadri, CEO of Abeona