Romosozumab (1) – Evenity®

• Clinical trials
  • The ARCH study was a randomised, double-blind, multicentre, two-arm, parallel-group trial investigating romosozumab followed by alendronic acid compared with alendronic acid alone in postmenopausal women with severe osteoporosis and a significant risk of fracture.

Postmenopausal women with established osteoporosis and a significantly increased risk of fracture

• For the treatment of established osteoporosis in postmenopausal women with a significantly increased risk of fracture, there is an indication for a minor additional benefit.
• When the results for patient-relevant endpoints are considered as a whole, a clear advantage – the prevention of fractures, which is particularly relevant in this indication – is offset by the negative effect of cerebrovascular side effects.
• In its decision-making process, the G-BA concludes that romosozumab followed by alendronic acid, compared with alendronic acid alone, offers a minor additional benefit in the treatment of established osteoporosis in postmenopausal women with a significantly increased risk of fracture.
• Due to the overall minor potential for bias at the study and endpoint levels, the certainty of the evidence for the identified additional benefit is classified as an indication.
• mortality
  • For the endpoint of all-cause mortality, no statistically significant difference was observed between the treatment groups in the ARCH study over the entire study period.
  • An additional benefit of romosozumab for all-cause mortality is therefore not proven.
• Morbidity – Clinical vertebral fractures
  • For the endpoint of clinical vertebral fractures, a statistically significant advantage was observed at month 24 between the treatment groups, in favour of romosozumab, followed by alendronic acid.
  • This indicates an advantage of romosozumab, followed by alendronic acid, compared with alendronic acid alone for the endpoint of clinical vertebral fractures.
• Morbidity – Major non-vertebral fractures
  • For the endpoint of major non-vertebral fractures, a statistically significant advantage was observed between the treatment groups at month 24, in favour of romosozumab, followed by alendronic acid.
  • The statistically significant advantage of romosozumab followed by alendronic acid was observed for hip and pelvic fractures.
• Morbidity – Non-major non-vertebral fractures
  • The endpoint ‘non-major non-vertebral fractures’ was not analysed separately.
• Morbidity – Most severe pain (mBPI-SF)
  • However, the data provided do not contain any usable information; consequently, this endpoint cannot be included in the assessment of the additional benefit of romosozumab.
• quality of life
  • In the analysis of the OPAQ-SV results, more than 30% of patients were excluded from the analysis at the relevant data cut-off point of month 24; consequently, regardless of the validity of the instrument, no usable data are available for the health-related quality of life endpoint.
  • The LAD consists of three individual questions and cannot therefore be regarded as a tool for assessing quality of life; in particular, it focuses on physical components, meaning that the LAD does not constitute a suitable construct for assessing health-related quality of life and, at best, addresses aspects of morbidity.
  • However, as it remains unclear overall which analysis method was used to analyse the collected data, the data presented are not taken into account for either quality of life or morbidity.
• Side effects – SAE and discontinuation due to AE
  • For the endpoints SAE and discontinuation due to AEs, no statistically significant difference was observed between the treatment groups in either case.
• Overall assessment / Conclusion
  • For the assessment of the additional benefit of romosozumab followed by alendronic acid, the results from the blinded, controlled, randomised parallel-group ARCH trial provide data on mortality (all-cause mortality), morbidity, quality of life and side effects compared with the appropriate comparator therapy (alendronic acid).
  • With regard to mortality, the data presented for the endpoint of overall mortality show no statistically significant difference in overall survival between the study arms.
  • For clinically significant vertebral fractures and major non-vertebral fractures (hip fractures and pelvic fractures), there were statistically significantly fewer fractures in the romosozumab group, followed by the alendronic acid group, compared with the alendronic acid group alone.
  • The extent of this effect is assessed as a marked improvement in treatment-related benefit.
  • The prevention of fractures represents an essential therapeutic goal in this indication.
  • No usable data are available for the 24-month treatment period to assess the impact of romosozumab followed by alendronic acid on quality of life.
  • With regard to side effects, romosozumab has a disadvantage in terms of a higher risk of cerebrovascular events.
  • At the end of the 24-month treatment phase, for both the overall study population and the patient population without pre-existing vascular disease, treatment with romosozumab followed by alendronic acid was associated with a higher incidence of cerebrovascular adverse events compared with alendronic acid alone .
• Overall assessment / Conclusion
  • For the assessment of the additional benefit of romosozumab followed by alendronic acid, the blinded, controlled, randomised parallel-group ARCH trial provides results on mortality (all-cause mortality), morbidity, quality of life and side effects compared with the appropriate comparator therapy (alendronic acid).
  • With regard to mortality, the data presented for the endpoint of overall mortality show no statistically significant difference in overall survival between the study arms.
  • For clinically significant vertebral fractures and major non-vertebral fractures (hip fractures and pelvic fractures), there were statistically significantly fewer fractures in the romosozumab group, followed by the alendronic acid group, compared with the alendronic acid group alone.
  • The extent of this effect is assessed as a marked improvement in treatment-related benefit.
  • The prevention of fractures represents an essential therapeutic goal in this indication.
  • No usable data are available for the 24-month treatment period to assess the impact of romosozumab followed by alendronic acid on quality of life.
  • With regard to side effects, romosozumab has a disadvantage in terms of a higher risk of cerebrovascular events.
  • At the end of the 24-month treatment phase, for both the overall study population and the patient population without a history of vascular disease, treatment with romosozumab followed by alendronic acid was associated with a higher incidence of cerebrovascular adverse events compared with alendronic acid alone .

Courtesy translation only, please refer to the German original.