The FDA has issued a complete response letter (CRL) to a biologics license application (BLA) for prademagene zamikeracel (pz-cel) because the agency said it needs more information to satisfy chemistry manufacturing and controls (CMC) requirements, according to a release from Abeona Therapeutics.1
The information requested by the FDA in its CRL is related to validation requirements for certain manufacturing and release testing methods. Some of these requirements were recorded during a pre-license inspection that took place at the company’s manufacturing facility in Ohio and was concluded on March 1.
Key Takeaways
- The FDA issued a complete response letter (CRL) to Abeona Therapeutics regarding its biologics license application (BLA) for prademagene zamikeracel (pz-cel), citing the need for more information to meet chemistry manufacturing and controls (CMC) requirements.
- The CRL requested additional information related to validation requirements for certain manufacturing and release testing methods, identified during a pre-license inspection at Abeona's manufacturing facility. Despite Abeona's response, the timing of data submission was insufficient for the FDA's review by the May 25 PDUFA date.
- Pz-cel is an investigational therapy for recessive dystrophic epidermolysis bullosa (RDEB), a genetic disorder causing blistering and wounds on the skin. Abeona plans to address the FDA's requests and resubmit the BLA in the third quarter of this year.
After the 2 week inspection, the FDA issued Abeona a Form 483 due to observations related to process controls.2 The company then submitted a response to the FDA on March 15 outlining steps taken to resolve the issues prior to BLA approval, with full reports provided after approval later this year.
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However, the FDA in its CRL said that the timing of the data which was to be submitted by Abeona would not give the agency enough time to complete its review by the May 25 prescription drug user fee act (PDUFA) date. The release from Abeona noted that the FDA did not identify any deficiencies in the efficacy or safety data in the BLA and did not request any additional clinical trials or clinical data.
“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…” Vish Seshadri, CEO of Abeona, said in a release.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.”
Pz-cel is an investigational autologous, COL7A1 gene-corrected epidermal sheet therapy for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), a genetic collagen disorder that leads to blistering wounds and scarring on the skin.3 The BLA for pz-cel, which was accepted and granted priority review in November, was supported by data from the phase 3 VIITAL study (NCT04227106) and a Phase 1/2 a study (NCT01263379).
The phase 3 VIITAL study evaluated the efficacy, safety and tolerability of pz-cel in 11 patients aged 6 years or older with RDEB. During the study, 43 large chronic wound pairs measuring greater than 20 cm2 of surface area that were open for a minimum of 6 months and a maximum of 21 years were treated with the therapy. Pz-cel met both primary endpoints, which were: the proportion of RDEB wound sites with greater than or equal to 50% healing from baseline, and pain reduction associated with wound dressing change.4 The therapy was well tolerated with no serious treatment-related adverse events.
“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,” Jean Tang, MD, PhD, principal investigator of the VIITAL study, said in a release at the time data from the study was announced.4 “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.”
Seshadri said in the release that the company anticipates re-submitting the BLA for pz-cel to the FDA in the third quarter of this year with all of the necessary updates to satisfy the deficiencies outlined in the CRL.1
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References
1. Abeona Therapeutics Provides Regulatory Update on Pz-cel. News Release. Abeona Therapeutics. April 22, 2024. Accessed April 23, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/276/abeona-therapeutics-provides-regulatory-update-on-pz-cel
2. Abeona Therapeutics Reports Full Year 2023 Financial Results and Announces Completion of FDA Inspections. News Release. Abeona Therapeutics. March 18, 2024. Accessed April 23, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/274/abeona-therapeutics-reports-full-year-2023-financial
3. Tang JY, Marinkovich MP, Lucas, E. et al. A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa. Orphanet J Rare Dis 16, 175 (2021). https://doi.org/10.1186/s13023-021-01811-7
4. 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 23, 2024. https://investors.abeonatherapeutics.com/press-releases/detail/243/abeona-therapeutics-announces-positive-topline-results-with
