VYJUVEK Kit, biological suspension and excipient gel for topical application Ref.[107249] Active ingredients: Beremagene geperpavec

5.1 Accidental Exposure to VYJUVEK

VYJUVEK is a genetically modified, herpes-simplex virus type 1 vector-based, replication-deficient, non-integrating gene therapy. VYJUVEK will not replicate in the subject’s cells and does not integrate into the subject cells' native genetic material. For precautions,

• Avoid direct contact with treated wounds (e.g., touching or scratching) and dressings of treated wounds for approximately 24 hours following treatment.
• Wear protective gloves when assisting subjects with changing wound dressings and handling the disposal.
• In the event of an accidental exposure (e.g., through a splash to the eyes or mucous membranes), flush with clean water for at least 15 minutes.

The most common adverse reactions (>5%) were itching, chills, redness, rash, cough, and runny nose.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in this section primarily reflect exposure to VYJUVEK gel in a randomized, intra-subject placebo‑controlled study. A total of 31 subjects with dystrophic epidermolysis bullosa (DEB), including 30 subjects with autosomal recessive DEB and one subject with autosomal dominant DEB received topical administration of VYJUVEK gel to their wounds. The age of the subjects ranged from 1 year to 44 years (mean age 17 years). Of the 31 subjects, 19 (61%) were pediatric subjects (less than 17 years of age), and 11 (36%) were females. Each subject received weekly topical application of VYJUVEK gel at one or more wound sites and placebo at a matching wound site as an intra-subject comparator. The median duration of exposure to VYJUVEK gel was 25 weeks. The most frequent adverse reactions (incidence >5%) observed in the study are summarized in Table 3. There were no discontinuations due to adverse reactions.

Table 3. Adverse Reactions (incidence >5%) Following Treatment with VYJUVEK gel (n=31):

In addition, the safety profile of VYJUVEK in two subjects with autosomal recessive DEB (RDEB) of six and seven months of age, respectively, who received topical VYJUVEK gel weekly in an open-label study was similar to the safety profile of VYJUVEK observed in the randomized, intra-subject placebo‑controlled study described above.

Risk Summary

There are no data with VYJUVEK gel use in pregnant women to inform a drug-associated risk. Animal developmental and reproductive toxicity studies have not been conducted with VYJUVEK.

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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

If the patient becomes pregnant while being administered VYJUVEK gel, the patient should be apprised of the potential hazards to the fetus and neonate. Women of childbearing potential should be advised to use an effective method of contraception to prevent pregnancy during treatment with VYJUVEK gel.

Risk Summary

There is no information available on the presence of VYJUVEK in human milk, the effects on the breastfed infant, or the effects on milk production. Animal lactation studies have not been conducted with VYJUVEK.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYJUVEK and any potential adverse effects on the breastfed child from VYJUVEK or from the underlying maternal condition.

No nonclinical or clinical studies were performed to evaluate the effect of VYJUVEK on fertility.

The safety and effectiveness of VYJUVEK gel was studied in pediatric patients. The safety and efficacy findings of VYJUVEK gel in pediatric patients were similar to safety and efficacy findings in adult patients [see Clinical Studies (14)].

Clinical studies of VYJUVEK gel did not include geriatric patients aged 65 years and over.