Eliglustat (2) – Cerdelga®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted results from the ELIKIDS study. This is a multicentre, open-label, uncontrolled and non-randomised Phase III study investigating the safety, efficacy and pharmacokinetics of eliglustat.

Children and adolescents aged 6 years and over, weighing at least 15 kg, with Gaucher disease type 1 (GD1), who are stabilised on enzyme replacement therapy and who, with regard to cytochrome P450 type 2D6 (CYP2D6) are slow (PMs), intermediate (IMs) or rapid metabolisers (EMs)

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• The strength of the evidence is summarised as ‘hint’.
• mortality
  • Fatalities were recorded as part of the safety monitoring. No fatalities had occurred by the data cut-off date of 21 June 2023.
  • Due to the single-arm study design, a comparative assessment of the data is not possible; no conclusion can be drawn regarding the extent of the additional benefit based on the mortality endpoint.
• Morbidity – bone pain
  • The endpoint of bone pain was assessed in the ELIKIDS study using a patient-reported question regarding the intensity of bone pain over the past 4 weeks, with 6 predefined response options.
  • At the start of the study, 96% of patients were pain-free and 4% experienced very mild pain. After 52 weeks, 90% of patients remained pain-free, whilst 4% reported very mild pain and 6% reported mild pain.
  • During the study, both analgesics and topical products for joint and muscle pain were used by 45% of patients in each case, which may bias the results for these endpoints.
  • Due to the single-arm study design, a comparative assessment of the data is not possible; no conclusion can be drawn regarding the extent of the additional benefit based on the bone pain endpoint.
• Morbidity – Fatigue assessed using the Paediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL Fatigue)
  • For the benefit assessment, self-reported measures are used, which are available for patients aged 5 years and over.
  • At baseline, the mean score was 76.6 points and at week 52 it was 75.4 points. There were therefore no marked numerical changes over the course of the study.
  • Due to the single-arm study design, a comparative assessment of the data is not possible; no conclusion can be drawn regarding the extent of the additional benefit based on the fatigue endpoint.
• Morbidity – Pain assessed using the Paediatric Quality of Life Inventory (PedsQL) Paediatric Pain Questionnaire
  • The PedsQL Paediatric Pain questionnaire assesses the extent of current pain (‘acute pain’) and the most severe pain experienced in the last 7 days, as well as the location of the pain.
  • For current pain, the mean score at baseline was 9.1 points and at week 52 was 10.0 points. The mean scores for the most severe pain over the past 7 days were 13.2 points at baseline and 14.7 points at week 52. There were therefore no marked numerical changes over the course of the study.
  • Due to the single-arm study design, a comparative evaluation of the data is not possible; no conclusions can be drawn regarding the extent of the additional benefit based on the endpoints ‘acute pain’ and ‘most severe pain over the past 7 days’.
• Morbidity – spleen volume
  • In the ELIKIDS study, spleen volume was measured using abdominal magnetic resonance imaging (MRI). Spleen volume was assessed by calculating the ‘multiple of normal’ (MN), which takes individual body weight into account.
  • Data are available for 46 patients. At baseline, the mean value in MN was 3.35; at week 52, it was 3.25. Overall, spleen volume thus remained largely stable over the course of the study.
  • A sustained reduction in pathologically enlarged spleen volume, combined with a noticeable reduction in debilitating symptoms and an improvement in quality of life for patients, is considered clinically relevant.
  • However, a comparative assessment of the data is not possible in this case due to the single-arm study design. No conclusion can be drawn regarding the extent of the additional benefit based on the endpoint of spleen volume.
• quality of life
  • Health-related quality of life was assessed using the Paediatric Quality of Life Inventory (PedsQL).
  • At baseline, the mean score was 80.3 points and at week 52 it was 79.5 points. There were therefore no marked numerical changes over the course of the study.
  • Due to the single-arm study design, a comparative assessment of the data is not possible; no conclusions can be drawn regarding the extent of the additional benefit for the quality of life category.
• Side effects
  • In addition to pharmacokinetic parameters, side effects were recorded as primary endpoints in the ELIKIDS study.
  • Four patients (8 %) experienced a severe AE; 5 patients (10 %) experienced a serious adverse event (SAE) and 7 patients (14 %) experienced an AE that led to discontinuation of the study medication.
  • Due to the single-arm study design, a comparative assessment of the data is not possible; no conclusion can be drawn regarding the extent of the additional benefit in the ‘side effects’ category.
• Overall assessment
  • The benefit assessment of eliglustat for the treatment of children and adolescents aged 6 years and over, weighing at least 15 kg, with type 1 Gaucher disease, who are stabilised on enzyme replacement therapy and who, with regard to cytochrome P450 type 2D6 (CYP2D6) are slow (PMs), intermediate (IMs) or rapid metabolisers (EMs), are based on the results of the single-arm ELIKIDS study.
  • Results are available on mortality, health status, health-related quality of life and side effects. Due to the single-arm study design, no comparative conclusions can be drawn; consequently, it is not possible to quantify the extent of the additional benefit on the basis of the data provided.
  • In its overall assessment of the available results, the G-BA classifies the extent of the additional benefit of eliglustat for the treatment of children and adolescents aged 6 years and over with a body weight of at least 15 kg who have type 1 Gaucher disease, who have been stabilised with enzyme replacement therapy and who are slow, intermediate or rapid metabolisers of cytochrome P450 type 2D6, as non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.