The FDA made the decision in response to manufacturing process information that it considered a major amendment.
The Prescription Drug User Fee Act (PDUFA) date for Krystal Biotech's B-VEC, an investigational, redosable gene therapy intended to treat dystrophic epidermolysis bullosa (DEB), has been extended to May 19, 2023, a 3-month extension from its original February 17, 2023, PDUFA date.1,2
The FDA made the extension based on manufacturing process information, which included information about the replacement of a hardware unit in the process’s concentration step and associated comparability data regarding its use. The information was provided by Krystal Biotech in December 2022 in response to an information request made by the FDA. While Krystal Biotech noted that processing parameters and product contact materials were not affected by the unit, the agency considered the change a major amendment necessitating an extension.
Krystal also noted that during the biologics license application (BLA) late-cycle review meeting, which was completed on December 15, 2022, the FDA informed the company that an Advisory Committee meeting and a Risk Evaluation and Mitigation Strategies program are unnecessary for the application. Proposed labeling discussions are scheduled to take place by April 20, 2023. Krystal Biotech also stated that pre-approval inspections of clinical sites and internal manufacturing and testing facilities are complete.
“While we are disappointed that this change was viewed as a major amendment, we are committed to working with the FDA as it completes its review of the B-VEC application,” Krish S. Krishnan, chairman and chief executive officer, Krystal Biotech, said in a statement regarding the news.1 “We will continue our commercial readiness efforts and upon approval bring this important treatment to DEB patients as soon as possible.”
The BLA for B-VEC was originally accepted by the FDA with priority review in August of last year. The BLA, which was submitted in June 2022, was supported by data from 2 intrapatient, placebo-controlled clinical trials: the phase 2 GEM-1/2 (NCT03536143) study and the phase 3 GEM-3 study (NCT04491604).1,2 A full data readout from the GEM-3 study was published in the New England Journal of Medicine last month.3 The data included the finding that 67% of wounds treated with B-VEC had complete healing at 6 months compared to 22% not treated with B-VEC in 31 patients (difference, 46%; 95% CI[24-68]; P = .002). In terms of safety, B-VEC was well-tolerated, with pruritis and chills noted as common adverse events.
“The impressive phase 3 results with B-VEC are the best we have seen to date in patients with DEB and, if approved, B-VEC provides hope for these patients suffering through debilitating and potentially life-threatening symptoms associated with the disease,” first author and primary investigator Peter Marinkovich, MD, director, Blistering Disease Clinic, Stanford Health Care, and Associate Professor of Dermatology, Stanford University School of Medicine, said in a December 2022 statement regarding the data’s publication.4
B-VEC is intended for topical application directly to DEB wounds and delivers 2 functional copies of the disease-targeted gene, COL7A1, to allow the skin cells to produce the normal COL7 protein.2 B-VEC previously received orphan drug designation from both the FDA and the European Medicines Agency (EMA) and fast track and rare pediatric disease designations from the FDA. It has also received regenerative medicine advanced therapy designation from the FDA and Priority Medicines eligibility from the EMA.1