Beremagene geperpavec

Identification

Summary

Beremagene geperpavec is gene therapy used to treat wounds associated with dystrophic epidermolysis bullosa.

Brand Names

Vyjuvek

Generic Name

Beremagene geperpavec

DrugBank Accession Number

DB17831

Background

Beremagene geperpavec is a live, replication-defective herpes simplex virus type 1 (HSV-1)-based vector therapy. Developed by Krystal Biotech, it was first approved by the FDA on May 19, 2023, for the treatment of wounds associated with dystrophic epidermolysis bullosa (DEB).⁵ DEB is caused by mutations in the COL7A1 gene that encodes collagen VII (COL7), a major component of the anchoring fibrils for dermal–epidermal cohesion.¹ Beremagene geperpavec is genetically modified to deliver COL7A1, thereby restoring the levels of the COL7 protein.⁴

Type

Biotech

Groups

Approved

Biologic Classification

Gene Therapies
Other gene therapies

Synonyms

B-VEC
Bercolagene telserpavec
Dna (recombinant herpes simplex virus type 1 strain kos plasmid vector kb103 human collagen col7a1-specifying)

External IDs

KB-103
KB103

Pharmacology

Indication

Beremagene geperpavec is indicated for the treatment of wounds in patients six months of age and older with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene.⁴

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Wound

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Beremagene geperpavec is a gene therapy that restores the deficient levels of human type VII collagen (COL7) protein.⁴ In RDEB mice and human RDEB xenografts, beremagene geperpavec restored C7 expression in keratinocytes and fibroblasts.¹ In a trial comprising patients with dystrophic epidermolysis bullosa, the topical administration of beremagene geperpavec was associated with greater wound healing at three and six months compared to placebo.³

Mechanism of action

Collagen VII (C7, COL7), encoded by the COL7A1 gene, is an anchoring fibril component that holds the epidermis and dermis together to maintain skin integrity.^1,2 COL7 is synthesized by epidermal keratinocytes and dermal fibroblasts.² Dystrophic epidermolysis bullosa (DEB) is an inherited disorder caused by COL7A1 gene mutations, leading to reduced or deficient levels of biologically active and functional COL7. Deficient levels of COL7 result in no functional anchoring fibrils and impaired dermal-epidermal adhesion.^1,2 DEB is associated with blistering, wounding, and scarring of the skin and other organs starting at birth.^1,4

Beremagene geperpavec is a herpes simplex virus type 1 (HSV-1)-based vector genetically modified to express COL7. Upon topical application to wounds, beremagene geperpavec enters both keratinocytes and fibroblasts and the vector genome is deposited in the nucleus. Once in the nucleus, transcription of the encoded human COL7A1 is initiated to produce and secrete COL7 by the cell in its mature form. COL7 molecules arrange themselves into long, thin bundles that form anchoring fibrils.⁴

Absorption

There is limited information available regarding the absorption of beremagene geperpavec. In an initial clinical study, viral vector DNA was detected in skin swab samples in all nine treated subjects, with a maximum level ranging from 5.1×10⁴ to 4.1×10⁸ vector genomes.⁴

Volume of distribution