Idelalisib (3) – Zydelig®

• Clinical trials
  • The dossier presented here sets out the results of the registration trial GS-US-312-0119 (idelalisib in combination with ofatumumab versus ofatumumab alone).

2) Idelalisib in combination with rituximab – first-line treatment in the presence of a 17p deletion or a TP53 mutation in patients for whom no other therapies are suitable

• The G-BA classifies the extent of the additional benefit of idelalisib in combination with rituximab as non-quantifiable, based on the criteria set out in Section 5(7) of the AM-NutzenV, taking into account the severity of the disease and the therapeutic objective in the treatment of the disease.
• There is a hint of additional benefit compared with the appropriate comparator therapy, best supportive care; however, this additional benefit is non-quantifiable because the available scientific data do not permit this.
• Morbidity – Progression-free survival (PFS)
  • Results of the GS-US-312-0116 study for the 17p-deletion or TP53-mutation patient population:
• Morbidity – Overall Response Rate (ORR)
  • Results from the GS-US-312-0116 trial for the 17p deletion or TP53 mutation patient population:
• Overall review
  • An overall review of the results of the marketing authorisation trial GS-US-312-0116 suggests a hint of an additional benefit compared with the appropriate comparator therapy (best supportive care); however, this is non-quantifiable because the available scientific data do not permit this.
  • A subgroup analysis shows, for patients with 17p-deletion or TP53 mutation, with regard to progression-free survival and the overall response rate, which the G-BA considers to be of particular relevance to healthcare provision for these study participants, who are classified as high-risk patients.
  • “This is a significant improvement for this high-risk sub-population, and its relevance is not diminished by the fact that the subjects in the study had previously been treated.”

1a) Patients who have received at least one prior course of treatment – patients with relapsed or refractory CLL for whom chemotherapy is indicated

• An additional benefit over the appropriate comparator therapy is not proven.
• The submitted dossier presents results from the registration trial GS-US-312-0119 (idelalisib in combination with ofatumumab versus ofatumumab) without using these to derive any additional benefit.
• In the pharmaceutical manufacturer’s assessment, the patient population included in the study cannot be fully assigned to either patient population 1a or patient population 1b.
• The pharmaceutical manufacturer has not carried out any additional analyses in the dossier to address this point.
• Consequently, there are no relevant data available for assessing the additional benefit of idelalisib in combination with ofatumumab.

1b) Patients who have received at least one prior course of treatment – patients with relapsed or refractory CLL for whom chemotherapy is not indicated

• An additional benefit over the appropriate comparator therapy is not proven.
• The submitted dossier presents results from the registration trial GS-US-312-0119 (idelalisib in combination with ofatumumab versus ofatumumab) without using them to establish additional benefit.
• In the pharmaceutical manufacturer’s assessment, the patient population included in the study cannot be fully assigned to either patient population 1a or patient population 1b.
• The pharmaceutical manufacturer has not carried out any additional analyses in the dossier to address this point.
• Consequently, no relevant data are available for assessing the additional benefit of idelalisib in combination with ofatumumab.

2) Ofatumumab – first-line treatment in the presence of a 17p deletion or a TP53 mutation in patients for whom no other therapies are suitable

• An additional benefit compared with the appropriate comparator therapy is not proven.
• No relevant data were presented to assess the additional benefit of idelalisib in combination with ofatumumab in this patient population.

Courtesy translation only, please refer to the German original.