Vyjuvek

VYJUVEK is indicated for the treatment of wounds in adult and pediatric patients with dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. VYJUVEK is a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy indicated for the treatment of wounds in adult and pediatric patients with dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. (1)

VYJUVEK is an opalescent yellow to colorless biological suspension, mixed into excipient gel, for topical application. VYJUVEK biological suspension is supplied as a 1 mL extractable volume in a single-use vial with a green cap, at a nominal concentration of 5×10 9 PFU/mL. The excipient gel is a clear viscous solution supplied as a 1.5 mL fill volume in a separate single-use vial with a blue cap. VYJUVEK biological suspension (1 mL) is mixed into the excipient gel vial prior to administration. VYJUVEK is a biological suspension, mixed into excipient gel, for topical application. VYJUVEK biological suspension is supplied as a 1 mL extractable volume in a single dose vial at a nominal concentration of 5×10 9 PFU/mL. The excipient gel is supplied as a 1.5 mL fill volume in a separate single use vial. VYJUVEK biological suspension (1 mL) is mixed into the excipient gel vial prior to administration as VYJUVEK gel. ( 3 )

None. None. (4)

Accidental Exposure to VYJUVEK: Avoid direct contact with treated wounds and dressings of treated wounds until the next dressing change, following application. Clean the affected area if accidental exposure occurs. (5.1)

5.1 Accidental Exposure to VYJUVEK Accidental exposure to VYJUVEK may occur to close contacts and caregivers. VYJUVEK is a genetically modified, herpes-simplex virus type 1 vector-based, replication-deficient, non-integrating gene therapy. VYJUVEK will not replicate in the patient’s cells and does not integrate into the patient cells’ native genetic material. For precautions, Avoid direct contact with treated wounds (e.g., touching or scratching) and dressings of treated wounds until the next dressing change. Wear protective gloves when assisting patients with changing wound dressings and handling the disposal. In the event of an accidental exposure through a splash to the eyes or mucous membranes, flush with clean water for at least 15 minutes.

5.1 Accidental Exposure to VYJUVEK Accidental exposure to VYJUVEK may occur to close contacts and caregivers. VYJUVEK is a genetically modified, herpes-simplex virus type 1 vector-based, replication-deficient, non-integrating gene therapy. VYJUVEK will not replicate in the patient’s cells and does not integrate into the patient cells’ native genetic material. For precautions, Avoid direct contact with treated wounds (e.g., touching or scratching) and dressings of treated wounds until the next dressing change. Wear protective gloves when assisting patients with changing wound dressings and handling the disposal. In the event of an accidental exposure 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. The most common adverse drug reactions (incidence >5%) were itching, chills, redness, rash, cough, and runny nose. (6) To report SUSPECTED ADVERSE REACTIONS, contact Krystal Biotech, Inc. at 1-844-557-9782 or FDA at 1-800-FDA-1088 or http://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 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 reflects exposure to VYJUVEK gel in a randomized, intra-patient placebo‑controlled study. A total of 31 patients with dystrophic epidermolysis bullosa (DEB), including 30 patients with autosomal recessive DEB and one patient with autosomal dominant DEB received topical administration of VYJUVEK gel to their wounds. The age of the patients ranged from 1 year to 44 years (mean age 17 years). Of the 31 patients, 19 (61%) were pediatric patients (less than 17 years of age), and 11 (36%) were females. Each patient 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) Adverse Reactions Patients n (%) Itching 3 (10) Chills 3 (10) Redness 2 (6) Rash 2 (6) Cough 2 (6) Runny Nose 2 (6) In addition, the safety profile of VYJUVEK in two patients 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-patient placebo‑controlled study described above.

6.1 Clinical Trials Experience 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 reflects exposure to VYJUVEK gel in a randomized, intra-patient placebo‑controlled study. A total of 31 patients with dystrophic epidermolysis bullosa (DEB), including 30 patients with autosomal recessive DEB and one patient with autosomal dominant DEB received topical administration of VYJUVEK gel to their wounds. The age of the patients ranged from 1 year to 44 years (mean age 17 years). Of the 31 patients, 19 (61%) were pediatric patients (less than 17 years of age), and 11 (36%) were females. Each patient 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) Adverse Reactions Patients n (%) Itching 3 (10) Chills 3 (10) Redness 2 (6) Rash 2 (6) Cough 2 (6) Runny Nose 2 (6) In addition, the safety profile of VYJUVEK in two patients 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-patient placebo‑controlled study described above.

No drug interaction studies have been performed.

8.1 Pregnancy 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.

8.2 Lactation 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.

8.3 Females and Males of Reproductive Potential No nonclinical or clinical studies were performed to evaluate the effect of VYJUVEK on fertility.

8.4 Pediatric Use The safety and effectiveness of VYJUVEK have been established in pediatric patients with dystrophic epidermolysis bullosa (DEB). The use in pediatric patients (0 to 16 years of age) was supported by evidence from adequate and well-controlled study which included 19 pediatric patients 1 year of age and older. [ see Adverse Reactions ( 6 ) Clinical Studies (14) ].

8.5 Geriatric Use Clinical study of VYJUVEK gel did not include geriatric patients aged 65 years and older.

Dystrophic epidermolysis bullosa (DEB) is caused by mutation(s) in the COL7A1 gene, which results in reduced or absent levels of biologically active COL7. Upon topical application to the wounds, VYJUVEK can transduce both keratinocytes and fibroblasts. Following entry of VYJUVEK into the cells, the vector genome is deposited in the nucleus. Once in the nucleus, transcription of the encoded human COL7A1 is initiated. The resulting transcripts allow for production and secretion of COL7 by the cell in its mature form. These COL7 molecules arrange themselves into long, thin bundles that form anchoring fibrils. The anchoring fibrils hold the epidermis and dermis together and are essential for maintaining the integrity of the skin. Patients with autosomal dominant DEB (DDEB) have lower than normal functional anchoring fibrils, and patients with RDEB have no functional anchoring fibrils.