VYJUVEK

Vyjuvek should be initiated by healthcare professionals experienced in the management of patients with dystrophic epidermolysis bullosa. Posology Vyjuvek is applied cutaneously to wound(s) once a week in small droplets in a grid- like pattern, approximately 1-cm by 1-cm apart.

All wounds may not be possible to be treated at each treatment visit. The recommended total maximum weekly dosing for children from birth up to 3 years old is 1 mL (2×109 PFU). The recommended total maximum weekly dosing for children above 3 years of age, adolescents, and adults is 2 mL (4×109 PFU).

Vyjuvek should be applied to wounds until they are closed before selecting new wound(s) to treat. Weekly treatment of previously treated wounds should be prioritised if they re-open. If no wounds are present, Vyjuvek should not be administered.

The table below provides a reference on dose per approximate size of the wound in children, adolescents, and adults. Table 1. 6 to < 2 PFU= plaque forming units. a: The maximum dose in children below 3 years of age is 1 mL (2×109 PFU) If a dose is missed, Vyjuvek should be administered as soon as possible, and weekly dosing should be resumed thereafter.

Special populations Elderly population No dose adjustment is required in patients ≥ 65 years old. 4). During preparation, administration, and disposal, appropriate precautions must be taken. g. gloves, mask, and eye protection) should be worn when handling Vyjuvek.

6). Administration For cutaneous use on wounds only. Prior to cutaneous use the suspension and gel must be thawed, and the suspension must be mixed into the gel in a pharmacy setting. 6. g. clinic) or the home setting. If deemed appropriate by the healthcare professional, trained patients or caregivers may also apply Vyjuvek.

Wounds should be gently cleaned prior to cutaneous administration using a product that does not contain a virucidal agent. 5). Table 2. Steps for administration Step 1. The Vyjuvek syringe should be primed prior to the initial application by pulling the plunger down and pushing it upwards, so that a small droplet of Vyjuvek forms at the tip of the syringe.

Step 2. Vyjuvek should be applied to the selected wound, in small droplets approximately 1-cm by 1-cm apart (width of a fingertip) with only the droplet touching the wound. Only the gel should contact the skin. The tip of the syringe should not touch the skin to prevent the contamination of the gel in the syringe.

Summary of the safety profile Eighteen patients (58%) in the clinical trial reported at least one adverse reaction. 7%).. No adverse reactions led to discontinuation. Tabulated list of adverse reactions Unless otherwise stated, the frequencies of adverse reactions are based on all causal adverse event frequencies identified in 31 patients exposed to beremagene geperpavec during a median duration of 25 weeks in the Phase 3 randomised, intra-subject placebo-controlled study.

1 for information on the main characteristics of patients in clinical trial. In the following table, adverse reactions are listed by MedDRA system organ class (SOC), preferred term, and by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The frequency of adverse reactions is defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000), not known (cannot be estimated from the available data).

Table 3. 7%) aged 3 years or less. Of the 19 paediatric subjects, 8 were female (42%). Given the identity of the product, and its route of administration and localized containment, frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

Immunogenicity There was minimal evidence of systemic vector exposure after cutaneous application of Vyjuvek. Antibodies against the viral vector (HSV-1) and transgene protein (COL7) were evaluated in a subset of subjects in the randomised, intra-subject placebo-controlled clinical study.

A total of 64% of evaluated subjects (14/22) were anti-HSV-1 antibody positive at baseline. Six of the 8 anti-HSV-1 seronegative subjects seroconverted by week 26 following treatment with Vyjuvek. For subjects with available matched baseline and end-of-study serum samples, anti-drug antibodies (ADAs) to COL7 were detected in 72% (13/18) of subjects treated with Vyjuvek for up to 26 weeks.

Traceability In order to improve the traceability of the biological medicinal product, the name and the batch number of the administered medicinal product should be clearly recorded. Squamous cell carcinoma Vyjuvek should not be applied to wounds with a confirmed or suspicious diagnosis of squamous cell carcinoma (SCC).

Vyjuvek may still be applied to other wounds in patients who develop SCC. Transmission of an infectious agent Beremagene geperpavec will not replicate in cells and does not integrate into or otherwise interact with the native DNA. Although beremagene geperpavec is tested for sterility, a risk of transmission of infectious agents exists.

Healthcare professionals administering Vyjuvek must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed. 6). Pregnant women should not handle dressing waste. Carers or HCPs applying the gel should comply with the requirement to cover wounds with dressings.

Patients should also be advised to avoid touching or scratching wound sites to avoid contamination of other areas of the body or close contacts. Long-term follow-up Patients are expected to enroll in a non-interventional multi-country study, to assess the long-term safety of beremagene geperpavec in a real-life setting.

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