Asciminib (1) – Scemblix®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the results of the data cut-off of 6 October 2021 from the randomised, controlled, open-label, multicentre Phase IIIASCEMBL trial, in which asciminib was compared with bosutinib in 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.

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

• Overall, the G-BA concludes that asciminib offers little added benefit compared with bosutinib for the treatment of adult patients 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, offers a minor additional benefit compared with bosutinib.
• Consequently, based on the ASCEMBL study, the G-BA finds an indication of a minor additional benefit for asciminib compared with bosutinib.
• mortality
  • No statistically significant difference was observed between the treatment arms for the endpoint of overall survival.
  • In the ASCEMBL study, overall survival is defined as the period between randomisation and the date of death from any cause.
• Morbidity – progression to blast crisis
  • In the ASCEMBL study, progression to blast crisis is defined as the period between randomisation and the date of the first occurrence of progression to blast crisis.
  • This endpoint is classified as patient-relevant, as progression to blast crisis is associated with a deterioration in the patient’s health status that is directly perceptible to them.
  • No statistically significant difference was observed between the two treatment arms for this endpoint. Only a minor number of events occurred in both arms.
• Morbidity – Severity of disease-related symptoms (MDASI-CML)
  • Symptoms were assessed in the ASCEMBL study using the patient-reported MDASI-CML symptom questionnaire prior to study-related procedures at the start of each visit during the treatment phase until the end of treatment.
  • The assessment of the severity of disease-related symptoms (20 items) and the impact of these symptoms on daily life (6 items) via the MDASI-CML is considered to be relevant to patients.
  • For the endpoint ‘severe severity of disease-related symptoms’, the MMRM analyses show a statistically significant difference in the mean change at week 8 in favour of asciminib compared with bosutinib. However, the 95% confidence interval for the standardised mean difference (Hedges’ g) does not lie entirely outside the irrelevance range of –0.2 to 0.2. Consequently, it cannot be concluded that the observed effect is clinically relevant.
• Morbidity – General health status (EQ-5D visual analogue scale)
  • General health status was assessed in the ASCEMBL study using the EQ-5D visual analogue scale prior to study-related procedures at the start of each visit during the treatment phase until the end of treatment.
  • For this analysis, no statistically significant difference between the treatment arms was identified at week 8.
• Morbidity – PGI-C
  • The PGI-C questionnaire consists of a single question used to assess the patient’s perception of whether their symptoms have improved or worsened during treatment.
  • For this analysis, no statistically significant difference between the treatment arms was identified at week 12.
• Conclusion on morbidity
  • The results show that, within the morbidity endpoint category for the endpoint ‘severity of disease-related symptoms’, a statistically significant difference in the mean change in favour of asciminib over bosutinib was observed only at week 8 in the MMRM analysis of the MDASI-CML. However, the 95% confidence interval for the standardised mean difference does not lie entirely outside the non-significant range of -0.2 to 0.2. Consequently, it cannot be concluded that the observed effect is clinically relevant. Overall, therefore, there are no relevant differences between the treatment arms with regard to morbidity.
• quality of life
  • No data on quality of life were submitted.
  • It is therefore not possible to assess the extent to which treatment with asciminib, compared with bosutinib, affects patients’ quality of life. Data on health-related quality of life are considered of high importance in the present treatment context.
• Side effects – serious adverse events (SAEs), severe adverse events (CTCAE grade ≥ 3), discontinuation due to adverse events
  • For the endpoints of serious adverse events (SAEs), severe AEs (CTCAE ≥ 3) and discontinuation due to AEs, a statistically significant advantage was observed between the treatment arms in favour of asciminib in each case.
  • With regard to severe AEs, in detail, Asciminib showed advantages over Bosutinib exclusively in the areas of investigations, gastrointestinal disorders and disorders of the skin and subcutaneous tissue.
• Side effects – AEs of particular interest
  • For AEs of particular interest, statistically significant differences in favour of asciminib compared with bosutinib were observed for gastrointestinal tumours (severe AEs), hepatotoxicity (including laboratory parameters) (severe AEs) and hypersensitivity (severe AEs). For grade ≥ 3 myelosuppression (thrombocytopenia), there is a statistically significant difference to the detriment of asciminib compared with bosutinib.
• Overall assessment
  • Data are available from the randomised, controlled, open-label, multicentre Phase III ASCEMBL study to assess the additional benefit of asciminib in the treatment of adult patients 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, the randomised, controlled, open-label, multicentre Phase III ASCEMBL trial provides results for the endpoint categories of mortality, morbidity and side effects compared with bosutinib.
  • In summary, there is a marked improvement in side effects. With regard to patient-relevant endpoints such as overall survival, symptoms, health status and progression to blast crisis, no significant differences are observed. No data are available on health-related quality of life.
  • On balance, the G-BA concludes that asciminib offers little added benefit compared with bosutinib for the treatment of adult patients 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, there is a minor additional benefit compared with bosutinib.

Courtesy translation only, please refer to the German original.