Etranacogen Dezaparvovec (1) – Hemgenix®

• Clinical trials
  • The HOPE-B trial is an open-label, single-arm, multicentre Phase III trial designed to assess the efficacy and safety of etranacogen dezaparvovec in adults with severe and moderate haemophilia B.
  • In addition, the open-label, single-arm Phase IIb trial CT-AMT-061-01 is presented; this trial included only three patients and, due to the minor sample size, is not used to derive any additional benefit.

Adults with severe and moderate haemophilia B (congenital factor IX deficiency) with no history of factor IX inhibitors

• For adults with severe and moderate haemophilia B (congenital factor IX deficiency) with no history of factor IX inhibitors, there is a hint of a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• Overall, there is a hint of a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• The strength of the evidence is therefore classified as a hint.
• mortality
  • One death occurred in the HOPE-B study.
• morbidity
  • Bleeding events and annualised bleeding rates (ABR)
  • The ABR endpoint is the primary endpoint of the HOPE-B study.
  • Approximately 43% of patients experienced no bleeding between day 22 and month 24 following administration of etranacogen dezaparvovec.
  • Furthermore, approximately 61% of patients experienced no Factor IX-treated bleeding events throughout the entire course of the study.
  • The estimated annualised bleeding rate (ABR) for ‘all bleeds’ is 1.01 and for ‘bleeds treated with factor IX’ is 0.82.
  • Factor IX activity
  • The endpoint ‘factor IX activity’ is a parameter that is not, in itself, clinically relevant to patients, as it is a laboratory parameter.
  • As the present before-and-after comparison is not recognised, no conclusions can be drawn regarding the extent of the additional benefit.
  • Furthermore, there are no data available on whether these are long-term effects.
• Quality of life – health status using the EQ-5D-5L VAS
  • Health status is assessed in the HOPE-B study using the visual analogue scale (VAS) of the EQ-5D-5L.
  • The data show an increase in scores for this endpoint from baseline to month 24.
  • As this before-and-after comparison is not recognised, no conclusions can be drawn regarding the extent of the additional benefit.
• Quality of life – functional impairment using the Haemophilia Activities List (HAL)
  • The HAL results show a change from baseline to month 24, suggesting a reduction in the degree of functional impairment.
  • As this before-and-after comparison is not recognised, no conclusion can be drawn regarding the extent of the additional benefit.
• Quality of life – pain assessed using the Brief Pain Inventory – Short Form (BPI-SF)
  • The results of the BPI-SF show a change from baseline to month 24, suggesting a reduction in the impact of pain.
  • As the present before-and-after comparison is not recognised, no conclusion can be drawn regarding the extent of the additional benefit.
• Quality of life – Haemophilia-specific Quality of Life Index for Adults (Ham-A-QoL)
  • Depending on the domain, mean changes of between 1 and 10 points were reported when comparing baseline to month 24, with the range of mean baseline values being 10–44 points.
  • Due to the uncontrolled design, no conclusions can be drawn regarding the effects of etranacogen dezaparvovec on quality of life.
• Side effects
  • As part of the safety endpoint analyses, no additional analyses were conducted that excluded disease-related events or events related to the underlying condition.
  • Adverse events occurred in all patients in the HOPE-B study.
  • Up to the 2-year data cut-off, 20% of the 54 patients experienced serious AEs and 26% experienced severe AEs.
  • In one patient, an AE led to the premature termination of the infusion, meaning that only a partial dose was administered.
• Overall assessment
  • Data are available from the single-arm study CT-AMT-061-02 (HOPE-B) on the endpoints of mortality, morbidity, quality of life and side effects.
  • In addition, a before-and-after comparison based on the HOPE-B study and an indirect comparison of etranacogen dezaparvovec (HOPE-B study) with albutrepenonacog (PROLONG-9FP study) were presented. Both of these comparisons are subject to major methodological limitations and are deemed insufficiently valid to be used for the benefit assessment.
  • Overall, there are no suitable data available for a comparative assessment. It is therefore not possible to quantify the extent of the additional benefit on the basis of the data presented.
  • Taking the available results as a whole, no conclusions can be drawn regarding the extent of the additional benefit. A quantitative assessment of the extent of the effect and a quantification of the additional benefit into one of the categories ‘minor’, ‘considerable’ or ‘major’ is not possible on the basis of the data provided. Taking into account the severity of the condition, the written submissions and the oral hearing, the G-BA classifies the extent of the additional benefit of etranacogen dezaparvovec for the treatment of severe and moderate haemophilia B in adults, on the basis of the criteria set out in Section 5(7) of the AM-NutzenV is non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.