Asciminib (3) – Scemblix®

• Clinical trials
  • Both studies are ongoing, open-label, randomised, controlled trials (RCTs) designed to investigate the efficacy and safety of asciminib in patients with newly diagnosed CML in the chronic phase.

a) Adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP), first-line treatment

• Hint for a considerable additional benefit
• Overall, the G-BA has determined that asciminib offers considerable additional benefit, based on the marked improvement in symptoms alongside a relevant improvement in quality of life and a reduction in side effects.
• The certainty of the established additional benefit is classified as a hint.
• mortality
  • In the ASC4FIRST and ASC4START studies, overall survival is defined as the period between randomisation and death from any cause.
  • For the endpoint of overall survival, no statistically significant difference between the treatment arms was observed either in the individual studies or in the meta-analysis of the ASC4FIRST and ASC4START studies.
• Morbidity – Progression to blast crisis
  • The endpoint ‘progression to blast crisis’ is defined in the ASC4FIRST and ASC4START studies as the period between randomisation and the first occurrence of progression to blast crisis, defined as ≥ 30% blasts in peripheral blood or bone marrow aspirate.
  • For the endpoint ‘progression to blast crisis’, no statistically significant difference between the treatment arms was observed either in the individual studies or in the meta-analysis.
• Morbidity – Symptoms (fatigue, nausea and vomiting, constipation, disease-specific symptoms)
  • With regard to symptoms, the meta-analysis presented showed statistically significant differences in favour of asciminib in the time to first worsening on the EORTC QLQ-C30 symptom scales for fatigue, nausea and vomiting, as well as constipation, and in the time to first worsening of disease-specific symptoms, as assessed using the EORTC QLQ-CML24.
  • For the morbidity endpoint category, this therefore results in an overall advantage for asciminib over the appropriate comparator therapy, which is based on the positive effects of asciminib with regard to the symptoms of fatigue, nausea and vomiting, as well as constipation, and disease-specific symptoms.
• Health-related quality of life – social functioning and impact on daily life
  • With regard to health-related quality of life, the meta-analysis of the ASC4FIRST and ASC4START studies showed a statistically significant advantage in favour of asciminib in the time to first deterioration in social functioning, as assessed using the EORTC QLQ-C30, as well as in the impact on daily life, assessed using the EORTC QLQ-CML24.
  • An advantage of Asciminib in terms of health-related quality of life can therefore be established.
• Side effects – severe adverse events (AEs) and therapy discontinuations due to AEs
  • For the endpoints of severe AEs and therapy discontinuations due to AEs, the meta-analysis of the ASC4FIRST and ASC4START studies revealed statistically significant advantages for asciminib.
  • With regard to severe AEs, a statistically significant difference in favor of asciminib was observed in the ‘vascular disorders’ system organ class.
  • For the endpoint category of side effects, an overall improvement can be inferred for asciminib compared with the appropriate comparator therapy, based on the positive effects observed for severe AEs and discontinuations due to AEs.
• Overall assessment
  • To assess the additional benefit of Asciminib for the treatment of adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP), the pharmaceutical manufacturer presented the results of a meta-analytical synthesis of the ASC4FIRST and ASC4START studies, in which asciminib was compared with other tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib, bosutinib).
  • With regard to overall survival, there was no statistically significant difference between the treatment arms.
  • In the morbidity endpoint category, advantages were observed for the endpoints of fatigue, nausea and vomiting, as well as constipation, as assessed using the EORTC-QLQ-C30. Furthermore, an advantage was observed in disease-specific symptoms, as assessed using the EORTC-QLQ-CML24.
  • In the quality of life category, asciminib showed an advantage due to improvements in social functioning, assessed using the EORTC QLQ-C30, and in the impact on daily life, assessed using the EORTC QLQ-CML24.
  • In the ‘side effects’ endpoint category, advantages for asciminib were observed for the endpoints of severe adverse events and therapy discontinuations due to adverse events. Specifically, a disadvantage for asciminib was observed in the vascular system organ class.
  • An overall assessment of the results for patient-relevant endpoints shows that asciminib leads to a significant improvement in symptoms, accompanied by a relevant improvement in quality of life and in the management of side effects.
  • Consequently, Asciminib is found to offer a considerable amount of additional benefit compared with the appropriate comparator therapy for the treatment of adults with newly diagnosed Ph+ CML-CP.

b) Adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who have previously been treated with a TKI; second-line therapy

• The additional benefit is not proven.
• An additional benefit of asciminib for adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who have previously been treated with a TKI is not proven.
• For the benefit assessment, the pharmaceutical manufacturer has provided a descriptive comparison of data from studies involving newly diagnosed patients (first-line, ASC4FIRST and ASC4START studies), patients with exactly one prior treatment (second-line, ASC2ESCALATE study) and patients with at least two prior treatments (ASCEMBL study), on the basis of which it justifies the transferability of the results for first-line treatment and for patients with at least two prior treatments to the second-line treatment setting.
• A descriptive comparison of data across different treatment lines is not considered suitable for assessing the additional benefit of asciminib for patients who have received exactly one prior treatment.

Courtesy translation only, please refer to the German original.