beremagene geperpavec (Rx)

1-10%

Itching (10%)

Chills (10%)

Redness (6%)

Rash (6%)

Cough (6%)

Runny Nose (6%)

Contraindications

None

Cautions

Drug is a genetically modified, herpes-simplex virus type 1 vector-based, replication-deficient, nonintegrating gene therapy; it will not replicate in subject’s cells and does not integrate into subject cells’ native genetic material

Avoid direct contact with treated wounds (eg, touching or scratching) and dressings of treated wounds for ~24 hr following treatment

Wear protective gloves when changing wound dressings and handling disposal

If accidentally exposed (eg, through a splash to eyes or mucous membranes), flush with clean water for ≥15 minutes

Pregnancy

There are no data with topical gel use in pregnant females to inform a drug-associated risk

No animal developmental and reproductive toxicity studies have been conducted

Clinical considerations

• If patient becomes pregnant during treatment, advise patient of potential hazards to fetus and neonate
• Advise females of childbearing potential to use an effective method of contraception to prevent pregnancy during treatment

Lactation

There is no information available on drug presence in human milk, effects on breastfed infants, or effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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 wounds, beremagene geperpavec can transduce both keratinocytes and fibroblasts; once into the cells, it is deposited in the nucleus and transcription of the encoded human COL7A1 is initiated

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

Anchoring fibrils hold the epidermis and dermis together and are essential for maintaining skin integrity

Patients with autosomal dominant DEB (DDEB) have lower than normal functional anchoring fibrils, and patients with recessive (RDEB) have no functional anchoring fibrils

Pharmacokinetics

No viral vector DNA was detected in blood or urine

No extracellular infectious particles were detected on skin surface of any subject at any timepoint tested, after topical application

Preparation

Vial

• Prepare gel at pharmacy by mixing biological suspension into excipient gel for immediate use within 8 hr of application
• If pregnant, do not prepare or apply gel and avoid direct contact with treated wounds or dressings from treated wound
• Wash hands and put on protective gloves
• Remove vial for biological suspension and excipient gel from carton and thaw vial at room temperature for ≥20 minutes
• Visually inspect vials to ensure both are in liquid form and completely thawed; excipient gel is more viscous and will take longer to thaw
• Invert biological suspension vial 4-5 times; do NOT invert the excipient gel vial
• Remove caps from vials and wipe each vial with a 70% isopropyl alcohol pad
• Aseptically connect an 18-gauge needle to 3-mL preparation syringe
• Hold vial at 45-90º, puncture vial, and withdraw 1 mL biological suspension into preparation syringe
• Remove preparation syringe (still connected to needle) containing 1 mL of biological suspension from vial; do NOT engage safety lock
• Discard biological suspension vial in biohazard waste
• Puncture excipient gel vial and transfer biological suspension into excipient gel vial
• Do NOT remove needle from excipient gel vial; lift bevel of needle above the liquid and pull plunger back to 1 mL mark
• Remove preparation syringe with 1 mL of air and engage safety lock
• Discard preparation syringe and needle into biohazard waste
• Place 70% isopropyl alcohol pad on top of the excipient gel vial stopper and shake vigorously for 10 seconds

Administration syringe

• Aseptically connect an 18-gauge needle to first 1-mL administration syringe and remove needle cap
• Hold vial at 45-90º, insert needle into excipient vial containing gel, and withdraw 0.4 mL of gel
• Note: An air pocket may form near plunger when extracting
• Do not remove needle from vial; lift bevel of the needle above gel and disconnect administration syringe containing 0.4 mL of prepared gel
• Disconnect administration syringe containing gel with air pocket visible
• Note: Leave needle in the excipient gel vial stopper
• Do not flick syringe to remove the air pocket; manipulate plunger up and down, until all air pockets have been removed
• Cap administration syringe and set aside
• Repeat above steps if multiple administration syringes are required
• Clean all surfaces that were in contact with biological suspension or gel and treat all spills with a virucidal agent such as 70% isopropyl alcohol, 6% hydrogen peroxide or <0.4% ammonium chloride; blot using absorbent materials
• Dispose all materials that may have come in contact with biological suspension or gel into a biohazard bag or container
• Place capped administration syringes containing gel in a sealable plastic bag.
• Place sealable plastic bag with administration syringes into an appropriate insulated secondary container at 2-8ºC (35.6-46.4ºF) for transport from preparation site to administration site

Topical Administration

Apply gel to selected wound(s) in droplets spaced evenly within the wound, ~1cm-by-1cm apart; resulting droplet pattern should loosely resemble a grid

Avoid touching administration syringe to skin

Recommended dose by wound size

• <20 cm²: 4 x 10⁸ PFU (0.2 mL)
• 20 to <40 cm²: 8 x 10⁸ PFU (0.4 mL)
• 40-60 cm²: 1.2 x 10⁹ PFU (0.6 mL)
• >60 cm²: Calculate total dose based on above until maximum weekly dose is reached

Using clean scissors, cut nonadherent hydrophobic dressing to a slightly larger size than wound and on dressing atop gel droplets

Cut standard dressing used by patient to a size slightly larger than hydrophobic dressing and place standard dressing atop hydrophobic dressing

Clean all surfaces that may have come in contact with gel and treat all spills with a virucidal agent such as 70% isopropyl alcohol, 6% hydrogen peroxide or <0.4% ammonium chloride; blot using absorbent materials

Discard unused administration syringes gel after preparation and any all materials (eg, syringe, cleaning materials) that may have come in contact with biological suspension or gel into a biohazard bag or container

Do not change wound dressing within approximately 24 hr after gel application

Missed dose

• If a dose is missed, apply gel as soon as possible and resume weekly dosing thereafter

Storage

Appropriate handling, preparation, application, and disposal of materials; follow universal biohazard precautions for handling

Unopen carton

• Freeze carton at -15ºC to -25ºC (5°F to -13ºF)
• If a freezer is not available, refrigerate at 2-8ºC (35.6-46.4ºF) for up to 1 month

Prepared administration syringes

• Room temperature at 20-25ºC (68-77ºF)) for up to 8 hr, OR
• If immediate use is not possible, may refrigerate at 2-8ºC (35.6-46.4ºF) for up to 48 hr