FDA Issues CRL for Abeona's Epidermolysis Bullosa Gene Therapy Pz-Cel


The FDA is requesting more CMC information, specifically with regard to validation requirements for specific manufacturing and release testing methods.

This is a developing story and will be updated with new information as it becomes available.

The FDA has issued a complete response letter (CRL) for the 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), according to an announcement from Abeona Therapeutics, the therapy’s developer.1

Via the CRL, the FDA is requesting more chemistry, manufacturing, and controls (CMC) information, specifically with regard to validation requirements for specific manufacturing and release testing methods. Abeona noted that the FDA did not take issue with any of the clinical efficacy or safety data included in the company's biologics license application (BLA) for pz-cel, and is not requesting additional clinical trials or clinical data. The CMC information was previously requested by the FDA in a March 2024 Late Cycle Review Meeting. Following this request, Abeona had provided the agency with plans indicating its intent to submit additional CMC data before pz-cel's approval and full validation reports after approval. Although, the FDA determined that the timing that Abeona suggested for the provision of this information would not allow the agency enough time to make a decision on pz-cel by its previously set Prescription Drug User Fee Act (PDUFA) of May 25, 2024, and hence issued the CRL.

“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 RDEB as quickly as possible,” Vish Seshadri, the chief executive officer of Abeona, said in a statement.1 “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.”

Abeona previously submitted its BLA for pz-cel in September 2023 after announcing a positive preBLA meeting in August.2,3 During this meeting, Abeona established that the efficacy and safety data seen with pz-cel so far would be enough to support the BLA submission and that retroviral vector manufactured at Abeona and Indiana University appear comparable based on provided data. The BLA was accepted with priority review on November 27, 2024.4

The BLA is supported by data from the phase 3 VIITAL study (NCT04227106) and a phase 1/2a study (NCT01263379).1 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.5 The study met both its primary end points of achieving over 50% wound healing and achieving a greater magnitude of pain reduction benefit at 6 months after treatment compared to baseline and control wounds. In terms of safety, pz-cel was well-tolerated with no serious treatment-related adverse events observed.

“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, Professor, Dermatology, Stanford University School of Medicine, said in a November 2022 statement. "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."

1. Abeona Therapeutics Provides Regulatory Update on Pz-cel. News release. Abeona Therapeutics. April 22, 2024. Accessed April 22, 2024. https://finance.yahoo.com/news/abeona-therapeutics-provides-regulatory-pz-200500676.html
2. 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 April 22, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/265/abeona-therapeutics-submits-biologics-license-application
3. 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 April 22, 2024. https://firstwordpharma.com/story/5775999?from=article
4. Abeona Therapeutics announces FDA accepts and grants priority review for Pz-cel biologics license application (BLA). News release. Abeona Therapeutics. November 27, 2023. Accessed April 22, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/268/abeona-therapeutics-announces-fda-accepts-and-grants
5. 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 April 22, 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
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