Obinutuzumab (5) – Gazyvaro®

• Clinical trials
  • To demonstrate additional benefit, the pharmaceutical manufacturer has submitted the results of the randomised, controlled, open-label, multicentre Phase III GADOLIN trial in the dossier.

Adults with follicular lymphoma (FL) who have not responded to treatment with rituximab or a rituximab-containing regimen, or who experienced disease progression during or up to 6 months after treatment

• The additional benefit is not proven.
• Consequently, it must be concluded that the additional benefit, as defined in Chapter 5, Section 18(1), fourth sentence, of the G-BA’s Rules of Procedure (VerfO), is not proven.
• mortality
  • The pharmaceutical manufacturer has not submitted complete analyses for all endpoints for any of the data sets submitted, in particular not for the final data set.
  • For the final data set dated 30 November 2018, the pharmaceutical manufacturer provides, in Module 4, only analyses of endpoints in the categories of mortality and side effects.
• morbidity
  • The analyses submitted for the patient-reported endpoints in the categories of morbidity and health-related quality of life are based on an earlier data cut-off date of 1 September 2014.
• Health-related quality of life
  • The analyses submitted for the patient-reported endpoints in the categories of morbidity and health-related quality of life are based on an earlier data cut-off date of 1 September 2014.
  • Health-related quality of life was assessed in the GADOLIN study using the FACT-Lym, which comprises five subscales.
  • The information on response rates was incomplete and was only available for selected analysis time points.
  • Similarly, the analyses presented using a mixed-measures repeated measures (MMRM) model for the FACT-G and the FACT-LymS subscale cannot be conclusively interpreted due to missing data.
• Side effects
  • The pharmaceutical manufacturer has not submitted complete analyses for all endpoints for any of the data cuts submitted, in particular not for the final data cut.
  • For the final data cut-off of 30 November 2018, the pharmaceutical manufacturer provides, in Module 4, only analyses for endpoints in the categories of mortality and side effects.
  • Furthermore, the data on adverse events submitted by the pharmaceutical manufacturer are incomplete.
  • Only adverse events, regardless of severity, that occurred in ≥ 10 per cent of patients in a study arm were reported.
• Summary of the assessment
  • The presentation of the study data in the dossier proved, in each instance, to be of serious extent inadequate and incomplete in terms of content, with the result that this precludes a proper assessment of the additional benefit.
  • The dossier did not contain analyses for all the endpoints recorded for any of the data sets, particularly not for the most recent one.
  • Furthermore, the analyses of health-related quality of life were inadequate.
  • Moreover, the results submitted on common adverse events were incomplete.
  • Even the analyses submitted subsequently with the written statement were not suitable for facilitating a proper assessment of the additional benefit due to their inadequate processing.
  • Consequently, it is therefore concluded that the additional benefit is not proven.

Courtesy translation only, please refer to the German original.