Ropeginterferon alfa-2b (1) – Besremi®

• Clinical trials
  • In the PROUD-PV trial, ropeginterferon alfa-2b was compared with the appropriate comparator therapy, hydroxyurea.
  • The CONTINUATION-PV study is an open-label Phase IIIb extension study investigating the long-term efficacy and safety of ropeginterferon alfa-2b in patients with polycythaemia vera who had previously participated in the PROUD-PV study.

a) Adult patients with polycythaemia vera who are either treatment-naiv or have been previously treated with hydroxyurea, without symptomatic splenomegaly, and who are neither resistant to nor intolerant of hydroxyurea

• An additional benefit is not proven.
• In summary, for untreated or hydroxyurea-treated adult patients with polycythaemia vera without symptomatic splenomegaly who are neither resistant to nor intolerant of hydroxyurea, an added benefit of ropeginterferon alfa-2b over hydroxyurea has not been demonstrated when considering the overall results regarding mortality, morbidity and side effects, additional benefit of ropeginterferon alfa-2b over hydroxyurea is not proven.
• mortality
  • For the overall survival endpoint, only one event occurred in the intervention arm and none in the control arm.
  • The presentation of an effect estimator is not informative.
  • Overall, the difference is not statistically significant.
  • An additional benefit of ropeginterferon alfa-2b for the mortality endpoint is not proven.
• Morbidity – Haematological response
  • The haematological response endpoint is defined as a haematocrit value < 45% in conjunction with a phlebotomy-free-free period of at least 3 months, as well as a platelet count < 400 × 10/L and a white blood cell count < 10 × 10/L.
  • For the post-hoc defined endpoint, which does not take spleen size into account, there is no statistically significant difference between the study arms (relative risk = 0.82 [0.64; 1.05]).
  • Consequently, the additional benefit of ropeginterferon alfa-2b for the haematological response endpoint is not proven.
• Morbidity – phlebotomies
  • With regard to the rate of phlebotomies performed due to a haematocrit of > 45%, no statistically significant differences were observed between the study arms for the entire 12-month study duration or for the titration phase (weeks 1–12).
  • For the maintenance phase (weeks 13–52), there was a statistically significant difference to the detriment of ropeginterferon alfa-2b (relative risk: 1.55 [1.19; 2.02]).
  • This difference is not considered sufficient to infer an overall disadvantage for the morbidity endpoint category.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint, as measured using the EQ-5D visual analogue scale (VAS), there are no statistically significant differences between the study arms.
  • An additional benefit of ropeginterferon alfa-2b for the health status endpoint is therefore not proven.
• quality of life
  • Data on health-related quality of life were not collected in the PROUD-PV study.
• Side effects
  • Adverse events (AEs) occurred at least once in > 80 % of patients in both study arms.
  • With regard to the endpoints of serious adverse events (SAEs), severe AEs (CTCAE Grade 3) and discontinuation due to AEs, there were no statistically significant differences between the study arms.
  • For the specific AEs ‘Gastrointestinal disorders’ (SOC), the sub-category ‘Nausea’ within this SOC, and the sub-category ‘Influenza’, there was a statistically significant advantage of ropeginterferon alfa-2b over hydroxyurea in each case.
  • Taking into account the clinical symptoms, the severity of the disease, and the nature and frequency of the adverse events, the advantages observed for these specific adverse events are assessed as an insignificant reduction in side effects.
  • Consequently, there are no differences between the study arms in the endpoint category of side effects that are relevant to the assessment.
• Overall assessment
  • For the endpoint of overall survival, there is no statistically significant difference between ropeginterferon alfa-2b and hydroxyurea.
  • For the morbidity endpoint category, there is no statistically significant difference between the study arms for the endpoints haematological response and health status (EQ-5D VAS).
  • For the endpoint ‘phlebotomies’, a statistically significant difference was observed to the detriment of ropeginterferon alfa-2b compared with hydroxyurea during the maintenance phase.
  • This difference is not considered sufficient to infer an overall disadvantage for the morbidity endpoint category.
  • Data on health-related quality of life were not collected in the PROUD-PV study.
  • For the endpoints SAE, severe AEs (CTCAE Grade 3) and discontinuation due to AEs, there were no statistically significant differences between the study arms in any case.
  • Advantages of ropeginterferon alfa-2b are evident for specific adverse events.
  • These advantages regarding the specific AEs are assessed, taking into account the clinical symptoms and the severity of the disease as well as the nature and frequency of the AEs, as an irrelevant reduction in side effects and therefore do not lead to the conclusion of any additional benefit.

b) Adult patients with polycythaemia vera without symptomatic splenomegaly who have been pre-treated with hydroxyurea and are resistant to or intolerant of hydroxyurea

• An additional benefit is not proven.
• For the group of adult patients with polycythaemia vera without symptomatic splenomegaly who have been previously treated with hydroxyurea and are resistant to or intolerant of hydroxyurea, no data have been presented to assess the additional benefit of ropeginterferon alfa-2b compared with the appropriate comparator therapy (ruxolitinib).
• Overall, therefore, an additional benefit of ropeginterferon alfa-2b is not proven for this patient population.

Courtesy translation only, please refer to the German original.