Lonapegsomatropin (1) – Skytrofa®

• Clinical trials
  • The heiGHt and CT-301-CN trials were randomised, open-label, actively controlled Phase III trials comparing lonapegsomatropin with a daily dose of somatropin over 52 weeks.

Children and adolescents aged 3 to < 18 years with growth disorder due to insufficient growth hormone secretion

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification
• Overall, the certainty of the evidence is classified as ‘hint’.
• mortality
  • No deaths occurred in the heiGHt and CT-301-CN studies.
• Morbidity – height (SDS)
  • Anthropometric parameters can be assessed as patient-relevant morbidity parameters, particularly in children with characteristic, disease-related growth disorders.
  • Standardised height was calculated using the Standard Deviation Score (SDS).
  • In the CT-301-CN study, an analysis was performed using ANCOVA. In the heiGHt study, in addition to the predefined analysis using MMRM, a non-pre-specified analysis using ANCOVA was carried out.
  • Whilst the CT-301-CN study showed a statistically significant advantage in favour of lonapegsomatropin in the analysis using ANCOVA, the heiGHt study revealed a statistically significant difference only in the non-predefined analysis using ANCOVA, but not in the predefined analysis using MMRM.
  • The significant difference in favour of lonapegsomatropin was also evident in the meta-analysis of both studies using ANCOVA.
  • However, the clinical relevance of the difference cannot be conclusively assessed.
  • For the subgroup characteristic ‘age’, the CT-301-CN study showed a statistically significant effect modification for the endpoint ‘height (SDS)’. Here, a significant advantage in favour of lonapegsomatropin compared with somatropin was observed in individuals under 6 years of age, whilst a smaller, non-significant effect was observed in individuals aged over 6 years.
• Morbidity – Annual growth velocity
  • The primary endpoint, growth velocity, describes the annual increase in standing height [cm/year] and is presented here 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 heiGHt and CT-301-CN studies, a statistically significant advantage in favour of lonapegsomatropin was observed for the growth rate endpoint.
• quality of life
  • No data on quality of life were collected.
• Side effects
  • Overall, only a few serious or severe adverse events (AEs) or therapy discontinuations due to AEs occurred.
  • No statistically significant difference was observed between the treatment groups for serious AEs, severe AEs and therapy discontinuations due to AEs.
  • Among the AEs of particular interest, the heiGHt study showed a statistically significant disadvantage for lonapegsomatropin compared with somatropin for the endpoints ‘abnormal reactions at the injection site’ and ‘redness’ respectively.
  • However, in the category of side effects, there are no overall advantages or disadvantages for lonapegsomatropin compared with somatropin.
• Overall assessment
  • For the endpoint in the morbidity category ‘height (SDS)’, the CT-301-CN study showed a statistically significant advantage in favour of lonapegsomatropin in the predefined analysis using ANCOVA. In the heiGHt study, a statistically significant advantage of lonapegsomatropin was observed in the non-predefined analysis using ANCOVA, but not in the predefined analysis using MMRM. The significant advantage in favour of lonapegsomatropin was also demonstrated in the meta-analytic analysis of both studies using ANCOVA.
  • Overall, however, the clinical relevance of the statistically significant difference in the endpoint ‘height (SDS)’ cannot be conclusively assessed, meaning that no conclusions can be drawn regarding the extent of the additional benefit.
  • Furthermore, there is a lack of long-term analyses that would allow an assessment of the subsequent course of growth.
  • In the category of side effects, the overall review reveals no advantages or disadvantages for lonapegsomatropin.

Courtesy translation only, please refer to the German original.