Rezafungin (1) – Rezzayo®

• Clinical trials
  • ReSTORE (study period 2018–2021) is a multinational, double-blind, randomised, active-controlled Phase IIIstudy investigating the efficacy and safety of rezafungin compared with caspofungin for the treatment of adults with candidemia and/or invasive Candida infection.
  • The multinational, exploratory, double-blind, randomised, active-controlled Phase II trial STRIVE (study period 2016–2019) also compared rezafungin with caspofungin.

Adults with invasive Candida infections

• For adults with invasive Candida infections, there is a hint of a non-quantifiable additional benefit, as the scientific evidence base does not permit quantification.
• Overall, the strength of the evidence is classified as a hint.
• mortality
  • Deaths were recorded continuously throughout the entire treatment period and at follow-up visits, up to day 52 (participants with candidemia alone in the STRIVE study) or day 59 (all other participants in the STRIVE and ReSTORE studies).
  • According to the data submitted during the commenting procedure, 64 people from the pooled population died, of whom 30 were in the intervention arms and 34 in the control arms.
  • However, it is unclear which data cuts were used for the analysis.
  • Due to the ambiguities in the measurement of the endpoint, the endpoint of all-cause mortality is not used for the benefit assessment and is presented only as supplementary information.
  • The data presented show no significant differences between the study arms.
• Morbidity – Global Cure
  • ‘Global cure’ is a composite endpoint comprising clinical, mycological and radiological (in individuals with invasive candidiasis) response.
  • The clinical relevance of the sub-component ‘mycological eradication’ is unclear.
  • The suitability of the ‘clinical response’ endpoint also remains unclear due to major uncertainties in its operationalisation.
  • Due to the unclear clinical relevance of the sub-component ‘mycological eradication’ and major uncertainties regarding the operationalisation of the ‘clinical response’ endpoint, the composite endpoint ‘global cure’ is presented for supplementary purposes only.
  • The analyses show no significant differences between the study arms.
• Morbidity – Overall response
  • ‘Overall response at day 14’ is the primary efficacy endpoint of the STRIVE trial.
  • This is a composite endpoint, the assessment of which as ‘success’ is based on the components ‘mycological eradication’ and ‘resolution of systemic signs and symptoms’.
  • The clinical relevance of the sub-component “mycological eradication” is unclear.
  • The suitability of the endpoint “resolution of attributable systemic signs and symptoms” also remains unclear due to major uncertainties in its operationalisation.
  • Consequently, the clinical relevance of the endpoint ‘overall response at day 14’ is also classified as unclear, and the results are presented for supplementary information.
  • Notwithstanding the uncertainties in operationalisation, the analysis reveals no statistically significant differences between the treatment arms.
• Morbidity – Mycological eradication
  • The endpoint ‘mycological eradication’ is a composite endpoint comprising the components ‘Candida-negative blood culture / Candida-negative culture from normally sterile body sites’, ‘need for treatment with further antifungals’ and ‘survival’.
  • The clinical relevance is assessed as unclear, as it has not been demonstrated to what extent documented or suspected mycological eradication constitutes a robust criterion for a long-term and sustained therapeutic effect.
  • The results for this endpoint are presented as a supplementary component of the combined primary endpoints; they show no significant differences between the study arms.
• quality of life
  • No data on health-related quality of life were collected.
• Side effects
  • Adverse events (AEs) and serious adverse events (SAEs) were recorded continuously throughout the study.
  • As no additional analyses excluding disease-related events are available, it cannot be ruled out that events related to the underlying disease were included in the AE data.
  • With regard to side effects, the results show no statistically significant differences between the treatment arms.
• Overall assessment / Conclusion
  • The results of the pivotal ReSTORE study and the supportive STRIVE study are available for this benefit assessment of the treatment of invasive Candida infection in adults.
  • In the mortality endpoint category, the overall survival endpoint is not used for the benefit assessment due to existing ambiguities in the data collection.
  • In the morbidity endpoint category, the endpoints ‘length of hospital stay’ and ‘length of stay in the intensive care unit’ were used for the benefit assessment.
  • In its overall assessment of the available results for patient-relevant endpoints, the G-BA classifies the extent of the additional benefit of rezafungin for the treatment of adults with invasive Candida infections, on the basis of the criteria set out in Section 5(8), first sentence, 2 in conjunction with Section 5(7), first sentence, number 4 of the AM-NutzenV as non-quantifiable, because the scientific evidence does not permit quantification.
• Overall assessment / Conclusion
  • The results of the pivotal ReSTORE study and the supportive STRIVE study are available for the present benefit assessment of the treatment of invasive Candida infection in adults.
  • In the mortality endpoint category, the endpoint of overall survival is not used for the benefit assessment due to existing ambiguities in the data collection.
  • In the morbidity endpoint category, the endpoints ‘length of hospital stay’ and ‘length of stay in the intensive care unit’ were used for the benefit assessment.
  • In its overall assessment of the available results on patient-relevant endpoints, the G-BA classifies the extent of the additional benefit of rezafungin for the treatment of adults with invasive Candida infections, on the basis of the criteria set out in Section 5(8), first sentence, 2 in conjunction with Section 5(7), first sentence, number 4 of the AM-NutzenV as non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.