Momelotinib (2) – Omjjara®

• Clinical trials
  • The pharmaceutical manufacturer has submitted results from the multicentre, randomised, double-blind, Phase III SIMPLIFY-1 trial for the benefit assessment, in which momelotinib was compared with ruxolitinib.
  • The SIMPLIFY-2 trial is a multicentre, randomised, open-label, Phase III trial in which momelotinib was compared with best available therapy (BAT).
  • The MOMENTUM study, presented as a supplement, is a multicentre, randomised, double-blind, Phase III study in which momelotinib was compared with danazol.

a) Adults with moderate or severe anaemia associated with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, who have not been treated with Janus-associated kinase inhibitors (JAK inhibitors); for the treatment of disease-related splenomegaly or symptoms

• The additional benefit is not proven.
• Overall, it is concluded that, for patients who have not been treated with JAK inhibitors, additional benefit is not proven for momelotinib compared with ruxolitinib.
• mortality
  • In the SIMPLIFY-1 trial, the endpoint of overall survival was defined as the time (in months) from the first dose in the blinded treatment phase until death, regardless of the cause of death.
  • No statistically significant difference was observed between the treatment arms.
• Morbidity – Leukaemic transformation
  • In the SIMPLIFY-1 trial, leukaemic transformation was defined as the time from randomisation to the occurrence of leukaemic transformation, defined as an increase in the blast count in the bone marrow of ≥ 20% or a blast count in peripheral blood of ≥ 20% in conjunction with an absolute blast count of ≥ 1 × 10/l for at least 2 weeks.
  • The results of the SIMPLIFY-1 study show no statistically significant difference between the treatment arms, with only one event observed in total.
• Morbidity – freedom from transfusions
  • For the present benefit assessment, post-hoc analyses of the proportion of patients who did not receive any transfusions of red blood cell concentrates over the entire 24-week observation period of the randomised controlled treatment phase are presented for transfusion-free status.
  • Due to the relevant uncertainties mentioned above, the results of SIMPLIFY-1 are assessed as insufficiently robust to derive any additional benefit from them.
• Morbidity – Symptoms assessed using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
  • Symptoms were assessed in the SIMPLIFY-1 study using the MPN-SAF at baseline and subsequently at 4-week intervals.
  • No statistically significant difference was observed between the treatment arms for the individual items of the MPN-SAF.
• Morbidity – Brief Fatigue Inventory (BFI)
  • The symptom ‘fatigue’ was assessed in the SIMPLIFY-1 study using the BFI.
  • No differences were observed between the treatment arms.
• Morbidity – Symptoms assessed using the Patient Global Impression of Change (PGIC)
  • In the dossier, the pharmaceutical manufacturer presents responder analyses for any improvement (‘very much improved’ to ‘slightly improved’) and any deterioration (‘slightly worsened’ to ‘very much worsened’) at week 24.
  • There is no statistically significant difference between the treatment arms.
• Morbidity – EQ-5D VAS
  • Health status was assessed in the SIMPLIFY-1 study using the EuroQoL 5-Dimensional (EQ-5D) visual analogue scale (VAS).
  • There is no statistically significant difference between the two treatment arms.
• Health-related quality of life
  • Quality of life was assessed in the SIMPLIFY-1 study using the Short Form Health Survey Version 2 (SF-36v2).
  • No difference in quality of life was observed between the treatment arms.
• Side effects – Serious adverse events (SAE) and severe adverse events (CTCAE grade ≥ 3)
  • There were no statistically significant differences between the treatment arms for SAE and severe AEs.
• Side effects – Therapy discontinuations due to adverse events (AEs)
  • For the endpoint of therapy discontinuations due to AEs, there was a statistically significant difference to the detriment of momelotinib compared with ruxolitinib.
• Side effects – Specific adverse events
  • In detail, the results for severe AEs (CTCAE grade ≥ 3) in the ‘anaemia’ PT show a statistically significant effect in favour of momelotinib compared with ruxolitinib.
  • In the ‘Nausea’ PT, a statistically significant effect was observed to the detriment of momelotinib compared with ruxolitinib.
• Conclusion on side effects
  • Overall, there are no statistically significant differences between the treatment arms in the endpoint category of side effects for SAE and severe AEs.
  • For the endpoint ‘therapy discontinuations due to AEs’, there is a disadvantage associated with momelotinib.
  • Due to the disadvantage regarding ‘therapy discontinuations due to side effects’, an overall disadvantage is inferred in the ‘side effects’ endpoint category.
• Overall assessment
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment groups.
  • In the morbidity endpoint category, no relevant differences were observed with regard to leukaemic transformation, although only one such event was recorded. No relevant differences were observed in the endpoints relating to symptoms (MPN-SAF, BFI, PGIC) or health status (EQ-5D VAS) either.
  • With regard to quality of life, as assessed using the SF-36v2, no major difference was observed.
  • With regard to the endpoint category of side effects, no statistically significant differences were observed between the treatment arms for the overall rate of SAE and severe AEs. There is a disadvantage associated with momelotinib in terms of ‘therapy discontinuations due to AEs’. Owing to this disadvantage in ‘therapy discontinuations due to AEs’, an overall disadvantage is inferred in the ‘side effects’ endpoint category.
  • Overall, for momelotinib compared with ruxolitinib in patients who have not been treated with JAK inhibitors, it is concluded that an additional benefit is not proven.

b) Adults with moderate or severe anaemia associated with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis who have been treated with ruxolitinib; for the treatment of disease-related splenomegaly or symptoms

• The additional benefit is not proven.
• Consequently, the SIMPLIFY-2 and MOMENTUM studies submitted by the pharmaceutical manufacturer are not suitable for demonstrating the additional benefit of momelotinib. There is therefore no evidence of additional benefit from momelotinib for the treatment of adults with moderate or severe anaemia associated with primary myelofibrosis, Post-polycythaemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis who have been treated with ruxolitinib is not proven.
• The treatment options used in the comparator arms of the SIMPLIFY-2 and MOMENTUM studies do not correspond to the appropriate comparator therapy as determined by the G-BA.

Courtesy translation only, please refer to the German original.