Somatrogon (1) – Ngenla®

• Clinical trials
  • To assess the additional benefit of Somatrogon for children and adolescents aged 3 years and over with growth disorders caused by insufficient growth hormone secretion, the pharmaceutical manufacturer submitted the open-label, randomised, controlled Phase III-trial CP-4-006, which formed the basis for marketing authorisation, in a parallel-group design with data collection up to month 12.
  • In the CP-4-006 study, Somatrogon was compared with Genotropin.

Children and adolescents aged 3 years and over with growth disorders caused by insufficient growth hormone secretion

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• Overall, for children and adolescents aged 3 years and over with growth disorders caused by insufficient growth hormone secretion, there is a hint of a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• mortality
  • No deaths occurred in the CP-4-006 study.
• Morbidity – height (z-score)
  • The anthropometric parameter of height is considered a patient-relevant morbidity parameter, particularly in children with characteristic, disease-related growth disorders.
  • No statistically significant difference was observed between the treatment groups for the endpoint ‘height (z-score)’.
• Morbidity – Growth velocity
  • The primary endpoint, growth velocity, describes the annual increase in standing height [cm/year] and is presented solely for supplementary purposes, as it does not provide any information on growth beyond standing height that is relevant to the benefit assessment.
  • In the CP-4-006 study, no statistically significant difference was observed between the treatment groups for the endpoint of growth velocity.
• Quality of life – Quality of Life in Short Stature Youth Questionnaire (QoLISSY)
  • The QoLISSY questionnaire is a tool for assessing the quality of life of children and adolescents with short stature, for which there is a version for direct questioning of children and adolescents in the age groups 8 to 12 years and 13 to 18 years, as well as a version for questioning the parents of affected children and adolescents in the age groups 4 to 7 years, 8 to 12 years and 13 to 18 years.
  • For the QoLISSY, the CP-4-006 study found no statistically significant difference between the treatment groups in terms of improvement of ≥ 15 points at month 12.
• Side effects
  • In the CP-4-006 study, no statistically significant difference was observed between the treatment groups for the endpoints of serious adverse events (SAEs) and severe adverse events.
  • In the CP-4-006 study, one person in the Somatrogon arm discontinued treatment due to an AE. Consequently, there was no statistically significant difference between the treatment groups for the endpoint of therapy discontinuations due to AEs.
  • At the SOC (System Organ Class) and PT (Preferred Term) levels, there was a statistically significant disadvantage for Somatrogon compared with Genotropin for the endpoints ‘General disorders and administration site conditions’, ‘Eye diseases’ (SOC), pain at the injection site (PT), a statistically significant disadvantage of Somatrogon compared with Genotropin was observed in each case.
  • For the endpoint ‘Investigations’ (SOC), a statistically significant advantage of Somatrogon over Genotropin was observed.
  • Among the AEs of particular interest, a statistically significant disadvantage of Somatrogon compared with Genotropin was demonstrated for the endpoints ‘injection site reactions’ and ‘immunogenicity’.
  • In the category of side effects, there are no overall advantages or disadvantages for Somatrogon compared with Genotropin.
• Overall assessment
  • The CP-4-006 study provides results on mortality, morbidity, quality of life and side effects.
  • No deaths occurred in the CP-4-006 study.
  • For the endpoint in the morbidity category, ‘body height (z-score)’, no statistically significant difference was observed between the treatment groups.
  • In the quality of life category, no statistically significant difference was found between the treatment groups for the QoLISSY endpoint.
  • In the ‘side effects’ category, the overall assessment reveals no advantages or disadvantages for Somatrogon.
  • Overall, there is a non-quantifiable additional benefit, as the scientific evidence does not allow for quantification.
• Validity of the evidence
  • For the submitted study CP-4-006, there is a high potential for bias at the study level due to the open-label study design.
  • In the CP-4-006 study, the diagnosis of GHD was confirmed by two different GH stimulation tests with a maximum GH concentration of ≤ 10 ng/ml, measured by a local or central laboratory. However, according to the current S2e guideline, a cut-off of < 8 ng/ml for the highest measured GH concentration in two GH stimulation tests is recommended for the diagnosis of growth hormone deficiency in children and adolescents. It therefore remains unclear whether all patients included in the CP-4-006 study have GHD.
  • It remains unclear whether the results from the CP-4-006 study at month 12 are also applicable to patients with a bone age of ≥ 10 to ≤ 14 years (girls) or ≥ 11 to ≤ 16 years (boys), .
  • Overall, with regard to the validity of the evidence, there is a hint of a non-quantifiable additional benefit.

Courtesy translation only, please refer to the German original.