Vosoritid (3) – Voxzogo®

• Clinical trials
  • Study 206 was a randomised, double-blind Phase II trial comparing vosoritid with placebo in children aged 0 to < 5 years with genetically confirmed achondroplasia over a period of 52 weeks.
  • Children who completed the placebo-controlled Study 206 subsequently had the opportunity to participate in the open-label extension study 208 and continue treatment with vosoritid.

Patients aged 4 months to < 2 years with achondroplasia whose epiphyses have not yet closed

• Overall, the G-BA therefore provides a hint of unquantified additional benefit for vosoritid in children aged 4 months to < 2 years with achondroplasia compared with the appropriate comparator therapy (BSC), taking into account the results for patients aged ≥ 2 years.
• Due to the uncertainty arising from the extrapolation of results from an older patient population to the younger patient population under assessment here, there is a hint of a non-quantifiable additional benefit.
• mortality
  • No deaths occurred in Cohort 2 of Study 206.
  • In Cohort 3, there was no statistically significant difference between the treatment groups.
• Morbidity – height (z-score)
  • For the endpoint of height (z-score), the meta-analysis of cohorts 2 and 3 of study 206 shows no statistically significant difference between the treatment groups.
  • Z-scores for height are derived using age- and sex-specific reference data for children of average stature.
• Morbidity – Annual growth velocity
  • For the endpoint annual growth velocity, the meta-analysis of cohorts 2 and 3 of Study 206 shows no statistically significant difference between the treatment groups.
• Morbidity – Upper-to-lower body segment ratio and limb proportions
  • However, the operationalisation of the endpoints ‘upper-to-lower body segment ratio’ and ‘body proportion ratios’ presented in the dossier does not allow for an assessment of any patient-relevant change in disproportion, as only the change compared with baseline was analysed.
  • No suitable data are available for the endpoints ‘ratio of upper to lower body segments’ and ‘body proportion ratios of the extremities’.
• Morbidity – Functional Independence (WeeFIM)
  • In Study 206, the WeeFIM was only administered from the age of 6 months onwards. Consequently, no suitable data are available for Cohort 3 (children aged 0 to < 6 months) to assess functional independence.
  • For cohort 2 (children aged ≥ 6 months to < 2 years), the endpoint of functional independence showed no statistically significant difference between the treatment groups, either in the total score or in the individual domains.
• Health-related quality of life – Infant and Toddler Quality of Life Questionnaire (ITQoL)
  • Taken as a whole, this means that there are no suitable data available for health-related quality of life, as assessed using the ITQoL, from which to derive any additional benefit.
• Side effects – Serious adverse events (SUEs)
  • For the endpoint of serious adverse events (SUEs), the meta-analysis of cohorts 2 and 3 of study 206 shows no statistically significant difference between the treatment groups.
• Side effects – severe adverse events
  • No events occurred in cohort 2 of Study 206 for the endpoint of severe adverse events. In cohort 3, there was no statistically significant difference between the treatment groups.
• Side effects – Discontinuation due to adverse events (AEs)
  • For the endpoint ‘discontinuation due to adverse events’, no events occurred in either Cohort 2 or Cohort 3 of Study 206.
• Side effects – injection site reactions (AE)
  • For the endpoint ‘AE at the injection site’, the meta-analysis of cohorts 2 and 3 of Study 206 showed a statistically significant disadvantage of vosoritid compared with BSC.
• Overall assessment
  • No statistically significant differences were observed between the two treatment arms in the endpoint categories of morbidity and side effects.
  • No suitable data are available for the quality of life endpoint category.
  • In summary, based on the results from Study 206, there are no statistically significant differences compared with BSC for children aged 4 months to < 2 years.
  • Overall, for children aged 4 months to < 2 years with achondroplasia whose epiphyses have not yet closed, with reference to the results of Study 206 (Cohort 1) and Study 301 in patients aged ≥ 2 years, an additional benefit of vosoritide over standard care (BSC) is observed. However, the extent of this additional benefit cannot be quantified due to the limited evidence available.

Courtesy translation only, please refer to the German original.