FDA Approves Abeona Therapeutics' Epidermolysis Bullosa Gene Therapy Pz-Cel
The agency's decision was based on data from the phase 3 VIITAL study (NCT04227106).
This is a developing story and will be updated with new information as it becomes available.
The FDA has approved Abeona Therapeutics' prademagene zamikeracel (pz-cel; EB-101), an autologous gene-corrected epidermal sheet therapy, for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB).1 The therapy will be marketed under the name Zevaskyn.
“Today’s approval of Zevaskyn represents a pivotal moment in the treatment of RDEB, answering the call of people living with the clinical, economic, and human impact of this devastating disease,” Vish Seshadri, PhD, MBA, the chief executive officer of Abeona, said in a statement.1 “We have heard from the RDEB community that there is a persistent unmet need to reliably address RDEB wounds, especially those that are chronic and prone to infection. Through a single surgical application, Zevaskyn can now offer people with RDEB the opportunity for wound healing and pain reduction in even the most severe wounds, as evidenced by the results from our pivotal phase 3 study.”
The agency's decision was based on results from the phase 3 VIITAL clinical trial (NCT04227106) and a phase 1/2a clinical (NCT01263379), both of which are now completed.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.3 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.
With regard to safety, the "Important Safety Information" for pz-cel notes that serious allergic reactions to the product are possible, and that any patients who develop itching, swelling, hives, difficulty breathing, runny nose, watery eyes, or nausea should immediately seek medical help.1 Furthermore, it is noted that anaphylaxis can happen in rare cases. Possible contribution to cancer development is listed as potential risk of pz-cel and it is noted that patients should be monitored for cancer for the duration of their lives. A risk of infection because of the product's derivation from human and animal materials is noted. Pain and itching constitute the most common treatment-related adverse events for patients undergoing treatment with pz-cel. Although, Abeona points out that these most common adverse events in VIITAL were seen in fewer than 5% of patients.
“Zevaskyn was well-tolerated and efficacious in clinical studies, providing clinically meaningful improvements in wound healing, pain reduction, and other associated symptoms in large chronic RDEB wounds after a single application,” lead principal investigator of VIITAL Jean Tang, MD, PhD, a professor of dermatology, added to the statement.1 “In the completed phase 1/2a study of Zevaskyn, we have observed wound healing and pain reduction that have lasted for years after a single application. Today we can celebrate the availability of an exciting new therapeutic option made possible by the incredible courage of patients and families who participated in these clinical studies.”
Abeona noted that it anticipates pz-cel will be available at qualified treatment centers in the third quarter of this year. Furthermore, the company stated that it will be providing personalized support, such as information on insurance benefits and travel and logistical help, for eligible patients via a patient services program referred to as Abeona Assist.
Notably, the FDA granted Abeona a rare pediatric disease priority review voucher in conjunction with pz-cel's approval. The company stated its intent to sell this voucher.
“Grafting gene-corrected skin onto chronically open wounds of patients with recessive dystrophic epidermolysis bullosa promises the potential to provide long-term healing of wounds, reduction in pain and reduced risk of infection," Amy Paller, MD, a pediatric dermatologist and clinical researcher, added to the statement.1 "This therapeutic option will nicely complement recently approved topical products.”
The biologics license application leading to the approval was a resubmission made by Abeona in October 2024 after an August 2024 Type A meeting held between the company and the FDA brought about alignment on a need for additional information related to Chemistry Manufacturing and Controls (CMC).4
The first BLA for pz-cel had been accepted by the FDA with priority review in November 2023, after Abeona submitted it to the agency in September 2023, but resulted in a complete response letter (CRL) from the agency in April 2024.4-7 The CRL specifically pertained to the FDA's desire for more CMC information with regard to validation requirements for specific manufacturing and release testing methods and did not suggest any concerns of the agency with regard to the efficacy and safety data supporting the BLA.
Pz-cel is derived from patient’s own skin cells that have been engineered ex-vivo to express a functional copy of COL7A1, the disease-targeted gene.2 The cells are expanded into keratinocyte sheets prior to being used to cover RDEB wounds via a surgical application process. Pz-cel is the second advanced therapeutic to be approved by the FDA for the treatment of RDEB, following the approval of Krystal Biotech’s gene therapy beremagene geperpavec (B-VEC, marketed as Vyjuvek in the United States) in May 2023.8
