Beremagene geperpavec is a gene therapy based on an engineered, replication-defective herpes simplex virus 1 (HSV-1) encoded with COL7A1 gene, addressing the underlying genetic cause of dystrophic epidermolysis bullosa. The HSV-1 vector belongs to the human herpes virus (HHV) family of double-stranded DNA viruses. Upon cutaneous application to the wounds, beremagene geperpavec can transduce both keratinocytes and fibroblasts. Following entry of beremagene geperpavec into the cells, the vector genome is deposited in the nucleus without integrating into, or otherwise disrupting, host cell DNA. 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.
In the confirmatory trial, systemic exposure assessments were conducted at weekly clinical site visits via quantification of beremagene geperpavec genomes in blood and urine samples (vector shedding) using a validated qPCR assay. All blood samples and all but one urine sample collected throughout the study were below the limit of detection/quantification for all subjects, indicating no significant systemic exposure of the subjects to the vector.
Biodistribution and vector shedding studies were supportive and indicated a lack of systemic exposure after localised, cutaneous administration of beremagene geperpavec.
Non-clinical data revealed no special hazard for humans based on conventional studies of single and repeated dose administration in toxicology studies.
Animal developmental and reproductive toxicity studies have not been conducted.
No studies have been conducted to evaluate the effects of beremagene geperpavec on carcinogenesis, mutagenesis, or impairment of fertility.
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