Source: FDA, National Drug Code (US) Revision Year: 2025
In patients with recessive dystrophic epidermolysis bullosa (RDEB), both copies of the COL7A1 gene are mutated, resulting in the absence or low levels of biologically active C7 protein which form anchoring fibrils (AFs). The lack of AFs disrupts the connection between the epidermis and the dermis and causes skin fragility and other signs and symptoms of RDEB. ZEVASKYN consists of a patient's own cells that have been gene-modified through RVV transduction to express the COL7A1 gene to produce the C7 protein. These cells are formed into cellular sheets for topical application onto wounds.
In a single-arm clinical study (n=7), C7 was assessed by both immunofluorescence and the presence of AFs at Months 3, 6, and 12. The NC2 domain of C7 was assessed using the LH24 antibody, and the presence of AFs was assessed by immunoelectron microscopy. The NC2 domain of C7 and AFs were detected in 6 patients at 3 months and in 5 patients at 6 months. One year after treatment with ZEVASKYN, 3 patients were positive for NC2 or AFs. At Year 2, 2 out of 3 patients with biopsies were positive for NC2 or AFs (1 patient was positive for both AFs and NC2; the second patient was positive only for NC2, as an additional biopsy for AF assessment was not obtained).
No clinical studies have been conducted to evaluate the pharmacokinetics of ZEVASKYN.
No carcinogenicity studies have been conducted with ZEVASKYN. Integration site analysis in RDEB keratinocytes transduced with LZRSE-Col7A1 showed a low level of integration distributed throughout the host genome with no predilection to specific integration sites, including in genes associated with malignant transformation in humans. No studies have been conducted to evaluate the effects of ZEVASKYN on fertility.
The efficacy of ZEVASKYN was evaluated in a multi-center, randomized, intrapatient-controlled study (VIITAL; NCT04227106). The study compared the application of ZEVASKYN to the standard of care treatment in patients with wounds associated with recessive dystrophic epidermolysis bullosa (RDEB). For enrollment, the patients were required to have at least one pair of matched, large (at least one wound ≥20 cm2 for treatment and at least one wound ≥20 cm2 for control) and chronic wounds (open for ≥6 months) associated with RDEB. Patients with current or history of squamous cell carcinoma (SCC) at the treatment site were excluded. Matched wound pairs were randomized in a 1:1 ratio to receive either ZEVASKYN (up to 6 sheets) or control treatment (standard of care wound dressings).
A total of 86 wounds in 11 patients were enrolled and treated with ZEVASKYN or standard of care in the study. The demographic characteristics of the population were as follows: the mean age was 23 years (range 6 to 40 years) including 2 pediatric patients (aged 6 and 16 years), 7 patients (64%) were female, 10 patients (91%) were White, 1 patient (9%) was of unknown race, and 2 patients (18%) were Hispanic or Latino. The wounds assessed in the study at baseline had been open for a median of 5 years (range 0.5-21 years).
The co-primary efficacy outcome measures were 1) proportion of randomized wound pairs with at least 50% healing at Month 6 with confirmation of wound healing two weeks later as assessed using baseline digital photography by the Investigator, and 2) pain reduction as assessed by the mean differences in patient-reported pain scores using the Wong-Baker FACES scale between randomized wound pairs at Month 6.1 Secondary outcome measures were proportion of randomized wound pairs with complete wound healing defined as reepithelialization with no drainage or erosion and presence of only minor crusting from baseline at Month 3 and at Month 6 with confirmation of wound healing two weeks later.
The efficacy results are summarized in Table 2.
Table 2. Efficacy results for VIITAL Study (N=86 wounds):
| Efficacy endpoint | ZEVASKYN (N=43 wounds) | Control (N=43 wounds) | P value |
|---|---|---|---|
| Proportion of randomized wound pairs healed ≥50% from baseline at Month 6a n (%) | 35 (81%) | 7 (16%) | <0.0001 |
| Mean pain reduction from baseline at Month 6b Mean (SD) | -3.07 (3.19) | -0.90 (2.73) | 0.0002 |
| Proportion of randomized wound pairs completely healed from baseline at Month 3 n (%) | 6 (14%) | 0 (0%) | 0.0316 |
| Proportion of randomized wound pairs completely healed from baseline at Month 6a n (%) | 7 (16%) | 0 (0%) | 0.0160 |
N=total number of observations; SD=Standard deviation; %=percentage
Complete wound healing is defined as re-epithelialization with no drainage or erosion and presence of only minor crusting.
a The proportion of wounds achieving success criteria at Month 6 must have been confirmed at least 2 weeks later.
b One wound was excluded from the control group due to missing baseline value.
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