Niraparib (3) – Zejula®

• Clinical trials
  • PRIMA is a multicentre, double-blind, randomised trial comparing niraparib with placebo.

Adult female patients with advanced epithelial (stages III and IV), high-grade carcinoma of the ovaries, fallopian tubes or primary peritoneal carcinoma, who are in remission (complete or partial) following completion of first-line platinum-based chemotherapy; maintenance therapy

• For maintenance therapy in adult female patients with advanced epithelial (FIGO stages III and IV) high-grade carcinoma of the ovaries, fallopian tubes or primary peritoneal carcinoma, who have shown a response (complete or partial) following platinum-based first-line chemotherapy, additional benefit is not proven.
• Consequently, the G-BA determines, in accordance with Chapter 5, Section 18, sentence 4 of the G-BA’s Rules of Procedure (VerfO), that the additional benefit is not proven.
• mortality
  • The pharmaceutical manufacturer presents results relating to the endpoint categories of mortality, morbidity, health-related quality of life and side effects in the dossier.
  • In its dossier assessment, the IQWiG found that the results of the PRIMA study submitted by the pharmaceutical manufacturer in the dossier were incomplete in terms of content and inadequately presented.
  • Consequently, IQWiG was unable to carry out an adequate assessment of the study data, meaning that the results of the PRIMA study were deemed unusable overall for the benefit assessment.
• morbidity
  • The pharmaceutical manufacturer presents results on the endpoint categories of mortality, morbidity, health-related quality of life and side effects in the dossier.
  • In its dossier assessment, the IQWiG found that the results of the PRIMA study submitted by the pharmaceutical manufacturer in the dossier were incomplete in terms of content and inadequately presented.
  • Consequently, IQWiG was unable to carry out an adequate assessment of the study data, meaning that the results of the PRIMA study were deemed, on the whole, to be unsuitable for use in the benefit assessment.
• Health-related quality of life
  • Health-related quality of life was assessed in the PRIMA study using the EORTC QLQ-C30 and EORTC QLQ-OV28 instruments.
  • In the dossier, the pharmaceutical manufacturer fails to present the analyses of the EORTC QLQ-C30 questionnaire in full and provides only results for the ‘global health status’ scale.
  • No justification for this selective reporting is provided in the dossier.
  • Due to the incomplete presentation of results from the core module EORTC QLQ-C30, the results of the disease-specific supplementary module EORTC QLQ-OV28 cannot be assessed either.
  • Consequently, extensive information on patient-reported endpoints was missing from the dossier assessment, and no analyses of health-related quality of life were available, even though this data had been collected.
• Side effects
  • Furthermore, the information in the pharmaceutical manufacturer’s dossier regarding adverse events (AEs) is incomplete.
  • For instance, only selected adverse events are presented for the ‘side effects’ endpoint category.
  • Of the common AEs, the pharmaceutical manufacturer reports only those SOCs and PTs for which a significant treatment difference was identified (hazard ratio or relative risk).
  • Furthermore, the pharmaceutical company lists the AEs that occurred in at least 10 patients receiving niraparib but not in those receiving placebo, and for which no HR or RR could be calculated.
• Overall assessment
  • In conclusion, the IQWiG states that, overall, due to the incomplete data, it is not possible to adequately weigh up the benefits and harms and thus to assess the additional benefit of niraparib compared with the appropriate comparator therapy.
  • Following a thorough examination of the IQWiG’s analysis of the shortcomings in the dossier, the G-BA concurs with the IQWiG’s assessment and, for its part, notes that, in accordance with Chapter 5, Chapter § 18(1) of the G-BA’s VerfO, the presentation of the documents in the dossier deviates from the requirements set out in Chapter 5 § 9 of the G-BA’s VerfO to such an extent that it precludes a proper assessment of the additional benefit.
  • The presentation of the data provided by the pharmaceutical manufacturer in this case does not meet the requirements set out in Chapter 5, Section 9 of the G-BA’s Procedural Rules (VerfO) and proves to be inadequate and incomplete, thereby precluding a proper assessment of the additional benefit.

Courtesy translation only, please refer to the German original.