Abeona Therapeutics Resubmits BLA to FDA for Epidermolysis Bullosa Gene Therapy Pz-Cel

Following the complete response letter (CRL) that Abeona Therapeutics received from the FDA earlier this year for the biologics license application (BLA) that the company submitted to the agency 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), Abeona has resubmitted the BLA for the therapy.¹

The company made the resubmission after reaching an accord with the FDA in a Type A meeting with the agency that took place in August 2024. Notably, in the meeting, Abeona came into alignment with the FDA on additional information pertaining to Chemistry Manufacturing and Controls (CMC).

In the CRL, which was issued to Abeona in April 2024, the FDA had 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,” Vish Seshadri, PhD, MBA, the chief executive officer of Abeona, said in a statement.¹ “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. Upon acceptance of the BLA, we look forward to assisting the FDA in the completion of its review.”

Abeona’s BLA for pz-cel was originally submitted to the FDA in September 2023 and accepted with priority review on November 27, 2024.^3-5 Data from the phase 3 VIITAL study (NCT04227106) and a phase 1/2a study (NCT01263379) support the BLA.²

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.⁶ Furthermore, the study’s primary end points—over 50% wound healing and a greater magnitude of pain reduction benefit at 6 months after treatment compared to baseline and control wounds—were both met. With regard to safety, pz-cel was characterized as well-tolerated, and no serious treatment-related adverse events were reported.

“I am incredibly enthused to see new clinical evidence of EB-101’s potential to treat the more difficult chronic and large wounds,” Brett Kopelan, the executive director of Dystrophic Epidermolysis Bullosa Research Association (debra) of America, said in a November 2022 statement.⁶ “Our patient community needs options to address not only the healing of wounds but also the chronic pain and the acute treatment related pain of daily wound care associated with these wounds. Today’s standard of care comprises hours of brutal and painful wound care, and EB-101’s promise to be a transformational option for RDEB patients is truly exciting."

CGTLive® has previously interviewed Kopelan about the potential of various advanced therapeutic options currently under development for DEB, including pz-cel. In the interview, which was conducted in October 2023 in observance of EB Awareness Week, which is held each year from October 25 to 31, Kopelan pointed out that some products may be better at treating large EB wounds and that others may be better filling in the gaps. Ultimately, he concluded that in the future, a combination of approaches is most likely to be successful in treating EB, rather than relying on a single therapeutic agent.

“I think when we are discussing being able to treat this disease effectively, we really need to look at a holistic approach to it...” Kopelan told CGTLive. “I can see in the near future where a patient is actually using more than one cell and gene therapy.”

REFERENCES
1. 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 October 31, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/291/abeona-therapeutics-completes-pz-cel-biologics-license
2. Abeona Therapeutics Provides Regulatory Update on Pz-cel. News release. Abeona Therapeutics. April 22, 2024. Accessed October 31, 2024. https://finance.yahoo.com/news/abeona-therapeutics-provides-regulatory-pz-200500676.html
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 October 31, 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 October 31, 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 October 31, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/268/abeona-therapeutics-announces-fda-accepts-and-grants
6. 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 October 31, 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