Beremagen geperpavec (1) – Vyjuvek®

• Clinical trials
  • For the benefit assessment of Beremagen geperpavec for the treatment of patients with wounds caused by dystrophic epidermolysis bullosa (DEB) with a mutation in the gene for the alpha-1 chain of type VII collagen (COL7A1), the pharmaceutical manufacturer presents results from the pivotal, multicentre, placebo-controlled, double-blind Phase III trial GEM-3, as well as from the single-arm, open-label extension trial (OLE) B-VEC-EX-02.

Patients with wounds resulting from dystrophic epidermolysis bullosa (DEB) with a mutation in the gene encoding the alpha-1 chain of type VII collagen (COL7A1)

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• For Beremagen geperpavec for the treatment of patients with wounds resulting from dystrophic epidermolysis bullosa with a mutation in the gene for the alpha-1 chain of type VII collagen, a non-quantifiable additional benefit is identified, as the scientific evidence does not permit quantification.
• mortality
  • Fatalities were recorded in both studies as part of the safety assessment. No fatalities occurred in either the GEM-3 study or the B-VEC-EX-02 study.
• Morbidity – complete wound closure
  • In the GEM-3 study, the endpoint of complete wound closure was predefined as the proportion of primary wounds with confirmed, complete wound closure from baseline to month 6, as well as the proportion of primary wounds with confirmed, complete wound closure from baseline to month 3.
  • For the endpoint of complete wound closure, the data at month 3, month 6, and at both month 3 and 6 each show a statistically significant advantage of Beremagen geperpavec over placebo.
  • The differences observed at the endpoint of complete wound closure indicate a clearly pronounced effect in favour of treatment with Beremagen geperpavec compared with the placebo control, which is not called into question despite the split-body design.
• Morbidity – pain during dressing changes
  • The endpoint of pain is generally regarded as clinically relevant in the therapeutic indication for epidermolysis bullosa.
  • As part of the commenting procedure, further information on the assessment of pain during dressing changes was submitted. Even though the assessments for the intervention and control groups were carried out sequentially, it is not possible to make a differentiated assessment between the intervention and control groups due to the systemic nature of the pain experienced. The criterion of local measurability is therefore not met, and a valid assessment is not possible due to the split-body design.
  • Overall, the results for the endpoint ‘pain during dressing changes’ are therefore presented only as supplementary data.
• Morbidity – symptoms assessed using Skindex-29
  • The ‘symptoms’ domain assessed using the Skindex-29 is relevant to patients.
  • The assessment of symptoms using the Skindex-29 relates to a person’s overall condition and, due to the split-body design, cannot be attributed to the intervention with Beremagen or the placebo control. A comparative statement is therefore not possible for this endpoint.
  • Due to uncertainties regarding the validity of the questionnaire for non-adult patients and the split-body design, the results of the Skindex-29 are presented for supplementary purposes only.
• Morbidity – General health status
  • General health status was assessed in the GEM-3 and B-VEC-EX-02 studies using the ‘European Quality of Life 5-Dimension 5-Level’ (EQ-5D-5L) questionnaire.
  • The EQ-5D-VAS score reflects a person’s overall health status and, due to the split-body design, cannot be attributed to the intervention with Beremagen or the placebo control. A comparative analysis is therefore not possible for this endpoint in the present study.
• quality of life
  • In the GEM-3 study, health-related quality of life was assessed using the Skindex-29 questionnaire. As described above, the domains ‘Emotion’ and ‘Function’ are assigned to the endpoint category of health-related quality of life. The ‘Emotion’ and ‘Function’ domains assessed using the Skindex-29 are relevant to patients.
  • As already explained, due to uncertainties regarding the validity of the questionnaire for non-adult patients and the split-body design, it is not possible to draw any comparative conclusions for this endpoint. The results of the Skindex-29 are therefore presented for supplementary purposes only.
• Side effects
  • Adverse events (AEs) were defined in the GEM-3 study as any adverse occurrence that occurred in a person who received the study medication.
• Overall assessment
  • For the benefit assessment of Beremagen geperpavec for the treatment of patients with wounds resulting from dystrophic epidermolysis bullosa with a mutation in the gene for the alpha-1 chain of type VII collagen, results are available from the placebo-controlled GEM-3 trial and the open-label extension study B-VEC-EX-02.
  • The placebo-controlled GEM-3 study was conducted using a split-body design. Each participant in the study had two comparable cutaneous wounds: one of these wounds was treated with the intervention Beremagen geperpavec, whilst the other wound served as a control and received a placebo. Due to the split-body design, the results presented relate to a person’s overall condition and – with the exception of the endpoint ‘complete wound closure’ – cannot be attributed specifically to the Beremagen geperpavec intervention or the placebo control. The study design therefore does not allow for any comparative conclusions between the intervention and the control group regarding the endpoint categories of mortality, health-related quality of life and side effects.
  • For the endpoint of complete wound closure, the data collected at month 3, month 6, and at both months 3 and 6 each show a statistically significant advantage of Beremagen geperpavec over placebo. The differences observed at the endpoint of complete wound closure indicate a clearly pronounced effect in favour of treatment with Beremagen geperpavec, which is not called into question despite the split-body design.
  • Overall, therefore, whilst there is a statistically significant advantage for the active ingredient (INN) Beremagen geperpavec over placebo for the endpoint of complete wound closure, the study design means that it is not possible to weigh up the benefits against the risks on the basis of the data presented. The data presented are therefore, on the whole, not suitable for quantifying the extent of the additional benefit.

Courtesy translation only, please refer to the German original.