Asciminib (2) – Scemblix®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the results of the ASCEMBL trial. This is a completed, multicentre, open-label RCT comparing asciminib with bosutinib.

a1) Adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who have previously been treated with two or more tyrosine kinase inhibitors, for whom bosutinib represents the appropriate individualised therapy

• Overall, a minor additional benefit is identified.
• The certainty of the evidence for the identified additional benefit is classified as an indication.
• mortality
  • In the ASCEMBL study, overall survival is defined as the time from randomisation to death from any cause. No statistically significant difference was observed between the treatment arms for the endpoint of overall survival.
• Morbidity – Progression to blast crisis
  • In the ASCEMBL study, blast crisis was defined as a proportion of ≥ 30% blasts in the blood or bone marrow. No statistically significant difference was observed for the endpoint ‘progression to blast crisis’.
• Morbidity – Symptoms and health status
  • Statistically significant advantages were observed in favour of asciminib compared with bosutinib for the endpoints of symptom severity and impairment of daily life due to symptoms, both assessed using the MDASI-CML.
  • For the endpoint ‘impact on daily life’, an effect modification by the characteristic of sex was observed. In this regard, an advantage for asciminib was observed only in the patient population of women. The results for the overall population are used for the assessment.
  • For the endpoints ‘symptoms’, assessed using the PGIC, and ‘health status’, assessed using the EQ-5D VAS, no statistically significant differences were observed between the treatment arms.
• Morbidity – impairment of activity (WPAI-CML question 6)
  • Results are available for question 6 of the WPAI-CML questionnaire. Question 6 of the WPAI-CML is classified under the category of morbidity. However, as the MDASI-CML (impact of symptoms on daily life) provides adequate coverage of patients’ activity impairment, the WPAI-CML is not used for assessment.
• quality of life
  • Endpoints relating to health-related quality of life were not assessed in the study.
• Side effects – Total adverse events (AEs)
  • In the ASCEMBL study, almost all randomised patients experienced at least one adverse event. The results are presented here for supplementary information only.
• Side effects – Serious adverse events (SAE), severe AEs (CTCAE grade ≥ 3)
  • For the endpoints ‘serious adverse events’ (SAEs) and ‘severe AEs’ (CTCAE grade ≥ 3), a statistically significant advantage was observed between the treatment arms in favour of asciminib.
• Side effects – Therapy discontinuation due to AEs
  • For the endpoint of discontinuation due to side effects, a statistically significant advantage was observed in favour of asciminib compared with bosutinib
• Side effects – Specific adverse events
  • For severe AEs, detailed analysis reveals advantages for disorders of the respiratory tract, thoracic cavity and mediastinum; disorders of the gastrointestinal tract; disorders of the skin and subcutaneous tissue; elevated alanine aminotransferase; and elevated aspartate aminotransferase. For the severe AE thrombocytopenia, a statistically significant difference in the disadvantage of asciminib is evident in detail.
• Overall assessment / Conclusion
  • To assess the additional benefit of asciminib for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who had previously been treated with two or more tyrosine kinase inhibitors, the ASCEMBL RCT was presented, in which asciminib was compared with bosutinib.
  • The results for the overall survival endpoint show no statistically significant difference between the treatment groups.
  • In the morbidity endpoint category, there were no statistically significant differences between the treatment groups for the endpoints of progression to blast crisis, symptoms (assessed using the PGIC) and health status (assessed using the EQ-5D VAS). Advantages were observed in the endpoints of symptom severity and impairment of daily life due to symptoms (assessed using the MDASI-CML), which were classified as moderate.
  • In the ‘side effects’ endpoint category, an advantage for asciminib was observed for serious adverse events (SAEs), severe adverse events (severe AEs) and discontinuation due to adverse events. In detail, advantages are observed for severe AEs relating to respiratory, thoracic and mediastinal disorders, gastrointestinal disorders, skin and subcutaneous tissue disorders, elevated alanine aminotransferase and elevated aspartate aminotransferase, as well as a disadvantage for the endpoint of thrombocytopenia (severe AEs). Overall, the results regarding side effects are assessed as a significant improvement.
  • In its cost-benefit analysis, the G-BA concludes overall that, for asciminib in the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who have previously been treated with two or more tyrosine kinase inhibitors, and for whom bosutinib represents the appropriate individualised therapy, there is a minor additional benefit compared with bosutinib.

a2) Adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who have previously been treated with two or more tyrosine kinase inhibitors, for whom nilotinib, dasatinib or ponatinib is the appropriate individualised therapy

• No additional benefit has been demonstrated for asciminib in the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukaemia in the chronic phase (Ph+ CML-CP) who have previously been treated with two or more tyrosine kinase inhibitors and for whom nilotinib, dasatinib or ponatinib is the appropriate individualised therapy, there is no proof that it is better than the appropriate comparator therapy.
• No data were presented for comparison with nilotinib, dasatinib or ponatinib.

Courtesy translation only, please refer to the German original.