VYJUVEK Suspension and gel for gel Ref.[115167] Active ingredients: Beremagene geperpavec

Pharmacotherapeutic group: Preparations for the treatment of wounds and ulcers, cicatrizants
ATC code: D03AX16

Mechanism of action

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.

Clinical efficacy and safety

The efficacy of Vyjuvek in subjects one year of age and older with DEB with mutation(s) in the COL7A1 gene was evaluated in a randomised controlled trial. All study subjects had DEB with genetically confirmed mutation(s) in the COL7A1 gene. Two comparable wounds in each subject were selected and randomised to receive either cutaneous application of beremagene geperpavec or placebo (gel only) weekly for 26 weeks. The total maximum weekly dose was defined based on age category: subjects ≥6 months to <3 years received 1.6×10⁹ PFU/week, subjects ≥3 years to <6 years received 2.4×10⁹ PFU/week, and subjects ≥6 years received 3.2×10⁹ PFU/week.

The study enrolled 31 subjects (20 males and 11 females), including 30 subjects with autosomal recessive DEB and one subject with autosomal dominant DEB. The size of the beremagene geperpavec-treated primary wounds ranged from 2 to 57 cm², with 74% of wounds <20 cm² and 19% from 20 to <40 cm². The size of the placebo gel-treated wounds ranged from 2 to 52 cm², with 71% of wounds <20 cm² and 26% from 20 to <40 cm². The largest size secondary wound treated was ≥130 cm². The mean age of the subjects was 17 years (1 year to 44 years), including 61% paediatric subjects (n=19, age 1 to <17 years) and 9.7% subjects less than 3 years. Sixty-four percent of subjects were White; 19% were Asian, and the remainder were American Indian or Alaska Native.

Efficacy was assessed on the basis of improved wound healing defined as the difference in the proportion of complete (100%) wound closure at 24 weeks confirmed at two consecutive study visits 2 weeks apart, assessed at weeks 22 and 24 or at weeks 24 and 26, between the beremagene geperpavec-treated and the placebo gel-treated wounds. Efficacy was also assessed by the difference in the proportion of complete wound closure assessed at weeks 8 and 10 or at both weeks 10 and 12 between the beremagene geperpavec-treated and the placebo gel-treated wounds. Complete wound healing was defined as 100% wound closure from the exact wound area selected at baseline, specified as skin re-epithelialization without drainage, evaluated at two consecutive visits two weeks apart. The efficacy results are summarised in Table 4.

Table 4. Primary end point and key secondary end point*:

^* The primary and key secondary end points were analysed in the intention-to-treat population.
Multiple-imputation methods were used to account for missing data. Fractional counts are due to the multiple-imputation procedure used for analysis. Hypothesis testing was performed with the use of exact McNemar’s test.
^† Primary wounds were assessed at weeks 22 and 24 or weeks 24 and 26.
^‡ Primary wounds were assessed at weeks 8 and 10 or weeks 10 and 12.