General Information

Vyjuvek (beremagene geperpavec-svdt) is a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy.

Vyjuvek is specifically indicated for the treatment of wounds in patients 6 months of age and older with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene.

Vyjuvek is supplied as a biological suspension mixed with excipient gel for topical application.

Dosing/Administration

• The recommended dose of Vyjuvek gel is based on age in the table below. Vyjuvek gel is applied topically to wound(s) once a week
• It may not be possible to apply Vyjuvek gel to all the wounds at each treatment visit.
• Apply Vyjuvek gel to wounds until they are closed before selecting new wound(s) to treat. Prioritize weekly treatment to previously treated wounds if they re-open.
•  If a dose is missed, apply Vyjuvek gel as soon as possible and resume weekly dosing thereafter.

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 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.

Side Effects

Adverse effects associated with the use of Vyjuvek may include, but are not limited to, the following:

• itching
• chills
• redness
• rash
• cough
• runny nose

Clinical Trial Results

The FDA approval of Vyjuvek was based on  two clinical studies. The GEM-1/2 trial was an intra-patient, open label, single center, randomized, placebo-controlled study showing that repeat topical applications of Vyjuvek were associated with durable wound closure, full-length cutaneous COL7 expression, and anchoring fibril assembly with minimal reported adverse events. The GEM-3 trial was an intra-patient, double-blinded, multi-center, randomized, placebo-controlled study that met both its primary endpoint of complete wound healing at six months and its key secondary endpoint of complete wound healing at three months.