FDA Accepts Abeona Therapeutics' BLA for Epidermolysis Bullosa Gene Therapy Pz-Cel

Abeona Therapeutics' biologics license application (BLA) for prademagene zamikeracel (pz-cel; EB-101), an investigational autologous gene-corrected epidermal sheet therapy for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), has been accepted for filing by the FDA.¹

The agency has set the Prescription Drug User Fee Act (PDUFA) action date for the BLA for April 29, 2025. Notably, the BLA is a resubmission, made by Abeona in October 2024 following a Type A meeting with the FDA that took place in August 2024 and in which the company reached an accord with the agency on necessary additional information pertaining to Chemistry Manufacturing and Controls (CMC).²

“The FDA acceptance of our BLA resubmission moves us one step closer to providing pz-cel as a differentiated treatment option to address the persistent unmet needs of people with RDEB in the US,” Vish Seshadri, PhD, MBA, the chief executive officer of Abeona, said in a statement.¹ “We look forward to continuing to work with the FDA to finalize the review of the pz-cel application.”

Abeona’s original BLA submission for pz-cel was made in September 2023 and accepted with priority review on November 27, 2023.^3-5 The original BLA was met with a complete response letter (CRL) from the FDA in April 2024, in which the agency requested more CMC information with regard to validation requirements for specific manufacturing and release testing methods.² Abeona noted that the FDA did not take issue with any of the clinical efficacy or safety data included in the company's BLA for pz-cel, and did not request additional clinical trials or clinical data.

“We have worked closely with the FDA in preparing for the pz-cel BLA resubmission and thank the Agency for their ongoing guidance,” Seshadri said in an October 2024 statement.² “We have incorporated the agency’s feedback and are confident that our resubmission package addresses all the CMC items identified in the CRL, including observations from the completed PreLicense Inspection of our manufacturing facility.”

The BLA is supported by data from the phase 3 VIITAL study (NCT04227106) and a phase 1/2a study (NCT01263379) that evaluated pz-cel, both of which are now completed.⁶ Results from VIITAL reported in November 2022 indicated that treatment with the therapy significantly improved wound healing and reduced pain in 11 participants with 43 wound pairs.⁷ Notably, VIITAL met its primary end points, with over 50% wound healing and a greater magnitude of pain reduction benefit at 6 months after treatment compared to baseline and control wounds reported.

“Large chronic RDEB wounds are the toughest to treat and often associated with intense chronic pain that significantly impacts the quality of life of RDEB patients, necessitating frequent use of opioids,” principal investigator Jean Tang, MD, PhD, a professor of Dermatology at Stanford University School of Medicine, said in a statement November 2022 statement.⁷ “In the phase 3 VIITAL study, EB-101 has been shown to both heal such large chronic wounds and significantly reduce pain. And we continue to see durable clinical benefit of EB-101 with up to 8 years of follow-up in our phase 1/2a study.”

Pz-cel is derived from patient’s own skin cells that have been engineered ex-vivo to express a functional copy of the disease-targeted COL7A1 gene.¹ The cells are expanded into keratinocyte sheets before being used to cover patients’ RDEB wounds in a surgical application. The FDA has granted pz-cel regenerative medicine advanced therapy, breakthrough therapy, orphan drug, and rare pediatric disease designations.⁷

If approved, pz-cel would not be the first advanced therapeutic to receive FDA approval for the treatment of RDEB. Krystal Biotech’s gene therapy beremagene geperpavec (B-VEC, marketed as Vyjuvek in the United States) was approved by the FDA on May 19, 2023.⁸ B-VEC is also currently under review for approval in the European Union.⁹ B-VEC is redosable and applied topically directly to DEB wounds and is the first gene therapy for a dermatological condition to have been approved in the US.⁸ It is intended to deliver 2 functional copies of COL7A1 via a herpes-simplex virus type 1 vector, to allow the skin cells to produce the normal COL7 protein.⁹

REFERENCES
1. Abeona Therapeutics® announces FDA acceptance of BLA resubmission of pz-cel for the treatment of recessive dystrophic epidermolysis bullosa. News release. Abeona Therapeutics Inc. November 12, 2024. Accessed November 13, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/294/abeona-therapeutics-announces-fda-acceptance-of-bla
2. Abeona Therapeutics® completes pz-cel biologics license application resubmission to U.S. Food and drug administration. News release. Abeona Therapeutics Inc. October 29, 2024. Accessed November 13, 2024.https://investors.abeonatherapeutics.com/press-releases/detail/291/abeona-therapeutics-completes-pz-cel-biologics-license
3. Abeona Therapeutics submits biologics license application to U.S. FDA seeking priority review and approval of EB-101 for the treatment of patients with Recessive Dystrophic Epidermolysis Bullosa. News release. Abeona Therapeutics. September 26, 2023. Accessed November 13, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/265/abeona-therapeutics-submits-biologics-license-application
4. Abeona Therapeutics Announces Positive Pre-BLA Meeting with FDA for EB-101 and Plans for BLA Submission. News release. Abeona Therapeutics. August 30, 2023. Accessed November 13, 2024. https://firstwordpharma.com/story/5775999?from=article
5. Abeona Therapeutics announces FDA accepts and grants priority review for Pz-cel biologics license application (BLA). News release. Abeona Therapeutics. November 27, 2023. Accessed November 13, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/268/abeona-therapeutics-announces-fda-accepts-and-grants
6. Abeona Therapeutics Provides Regulatory Update on Pz-cel. News release. Abeona Therapeutics. April 22, 2024. Accessed November 13, 2024. https://finance.yahoo.com/news/abeona-therapeutics-provides-regulatory-pz-200500676.html
7. Abeona Therapeutics announces positive topline results with both co-primary endpoints met in pivotal phase 3 VIITAL™ study of EB-101. News release. Abeona Therapeutics. November 3, 2022. Accessed November 13, 2024. https://www.globenewswire.com/news-release/2022/11/03/2547492/0/en/Abeona-Therapeutics-Announces-Positive-Topline-Results-with-Both-Co-Primary-Endpoints-Met-in-Pivotal-Phase-3-VIITAL-Study-of-EB-101.html
8. rystal Biotech Receives FDA Approval for the First-Ever Redosable Gene Therapy, VYJUVEK™ (beremagenegeperpavec-svdt) for the Treatment of Dystrophic Epidermolysis Bullosa. News release. Krystal Biotech. May 19, 2023. Accessed November 13, 2024. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-receives-fda-approval-first-ever-redosable-gene
9. Krystal Biotech announces EMA validation of marketing authorization application for VYJUVEK for the treatment of dystrophic epidermolysis bullosa. News release. Krystal Biotech, Inc. November 27, 2023. Accessed November 13, 2024. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-ema-validation-marketing-authorization