Prademagene Zamikeracel

ZEVASKYN is indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB). ZEVASKYN is an autologous cell sheet-based gene therapy indicated for the treatment of wounds in adult and pediatric patients with recessive dystrophic epidermolysis bullosa (RDEB). ( 1 )

ZEVASKYN is supplied as single-dose cellular sheets each measuring 41.25 cm 2 (5.5 cm x 7.5 cm) and consisting of patient's own viable, gene-modified cells that contain functional copies of the COL7A1 gene, which express collagen 7 (C7) protein. Up to twelve (12) C7-expressing cellular sheets are supplied for each surgical session (supplied as up to 3 containers containing up to 4 sheets). ZEVASKYN is supplied as a single-dose of up to twelve cellular sheets each measuring 41.25 cm 2 (5.5 cm x 7.5 cm) and consisting of patient's own, viable, gene-modified cells that contain functional copies of the COL7A1 gene, which express collagen 7 (C7) protein. ( 3 )

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Hypersensitivity reactions to vancomycin, amikacin, or product excipients may occur with ZEVASKYN application. ( 5.1 ) Retroviral vector (RVV)-mediated insertional oncogenesis may potentially occur after treatment with ZEVASKYN. ( 5.2 ) Transmission of Infectious Agents may occur because ZEVASKYN is manufactured using human- and bovine-derived reagents. ( 5.3 )

5.1 Hypersensitivity Reactions Severe hypersensitivity reactions to vancomycin, amikacin, or product excipients may occur with ZEVASKYN application. Monitor for signs and symptoms of hypersensitivity reactions such as itching, swelling, hives, difficulty breathing, runny nose, watery eyes, nausea, and in severe cases, anaphylaxis and treat according to standard clinical practice. 5.2 R etroviral Vector (R VV ) -Mediated I nsertional O ncogenesis RVV-mediated insertional oncogenesis may potentially occur after treatment with ZEVASKYN [see N onclinical T oxicology ( 13 ) ] . Monitor patients lifelong after treatment with ZEVASKYN for the development of malignancies. In the event that a malignancy occurs, contact Abeona Therapeutics Inc. at 1-844-888-2236 to obtain instructions on collecting patient samples for testing. 5. 3 Transmission of Infectious Agents Transmission of infectious disease or agents may occur with ZEVASKYN administration because it is manufactured using human and bovine-derived reagents, which are tested for human and animal viruses, bacteria, fungi, and mycoplasma before use. These measures do not eliminate the risk of transmitting these or other infectious diseases or agents.

The most common adverse reactions (incidence ≥5%) were procedural pain and pruritus. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Abeona Therapeutics Inc at 1-844-888-2236 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to the rates in the clinical trials of another product and may not reflect the rates observed in practice. The safety data described in this section reflects exposure of 11 patients to ZEVASKYN in the VIITAL study [see Clinical Studies ( 14 ) ] . The median number of sheets patients received was 6 (range 3-6), and the total exposure time was 6 months following ZEVASKYN application. The most common adverse reactions occurring in ≥5% of patients were procedural pain (n=3; 27%) and pruritus (n=1; 9%).

8.1 Pregnancy Risk Summary There are no available data with ZEVASKYN use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with ZEVASKYN. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy at the time of treatment with ZEVASKYN.

8.2 Lactation Risk Summary There is no information regarding the presence of ZEVASKYN in human milk, its effect on the breastfed infant, or its effects on milk production. Animal lactation studies have not been conducted with ZEVASKYN. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZEVASKYN and any potential adverse effects on the breast-fed infant from ZEVASKYN or from the underlying maternal condition. 8. 3 Females and Males of Reproductive Potential No studies were performed to evaluate the effect of ZEVASKYN on fertility. 8. 4 Pediatric Use The safety and effectiveness of ZEVASKYN have been established in pediatric patients. The use of ZEVASKYN in pediatric patients was supported by evidence from one clinical study which included two pediatric patients aged 6 years and 16 years [ see Adverse Reactions ( 6 ) and Clinical Studies ( 14 ) ] .

8.5 Geriatric Use The safety and effectiveness of ZEVASKYN have not been studied in geriatric patients ≥ 65 years of age.

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.