Belatacept (1) – Nulojix®

a) Patients who received a transplant from a donor selected according to standard criteria (SCD).

• For patients who received a transplant from a donor selected according to standard criteria (SCD), there is an indication of a minor additional benefit compared with the appropriate comparator therapy.
• Morbidity – Renal insufficiency at CKD stage 4/5
  • Analysis of the results of the BENEFIT study on renal function (cGFR) shows, using the Chronic Kidney Disease (CKD) staging system, that, after 36 months of treatment, a lower proportion of patients had CKD stage 4 or 5 renal insufficiency whilst on belatacept than whilst on the appropriate comparator therapy.
  • The extent of the additional benefit at the endpoint level is quantified as ‘minor’, as a moderate improvement is achieved.
• Side effects – overall rate of serious adverse events
  • After 36 months of treatment, fewer serious adverse events occurred in the belatacept arm of the study compared with the arm receiving the appropriate comparator therapy.
• Side effects – Discontinuations due to adverse events
  • Furthermore, therapy discontinuation due to adverse events occurred less frequently.
• With regard to the other endpoints underlying this benefit assessment – drawn from the categories of mortality, morbidity, health-related quality of life and side effects – there are no further differences in benefit between belatacept and the appropriate comparator therapy.
• With regard to the health-related quality of life endpoints, although there is a statistically significant difference in the mental health summary score in favour of belatacept, the magnitude of the effect is such that a clinically relevant difference cannot be assumed.
• The 95% confidence interval for this score does not lie entirely above the irrelevance threshold of 0.2 (Hedges’ g), meaning that additional benefit of belatacept for this endpoint is not proven.
• Overall assessment
  • In its overall assessment of all endpoints, the G-BA summarises the extent of the additional benefit, taking into account the severity of the disease, as ‘minor’.
  • The decisive factors for this assessment are the results at endpoint level for ‘renal insufficiency at CKD stage 4/5’, ‘overall rate of serious adverse events’ ” and “discontinuations due to adverse events”, which demonstrate a moderate improvement in patient-relevant benefit compared with the appropriate comparator therapy in accordance with Section 5(7) in conjunction with Section 2(3) of the AM-NutzenV.
  • A balancing test was not required.

a) Patients who received a transplant from an extended criteria donor (ECD)

• For patients who received a transplant from an extended criteria donor (ECD), there is an indication of a minor additional benefit compared with the appropriate comparator therapy.
• Morbidity – renal insufficiency with CKD stage 4/5
  • In the BENEFIT-EXT study, the proportion of patients with renal insufficiency at CKD stage 4 or 5 after 36 months of treatment was minor compared to the appropriate comparator therapy.
  • The extent of the additional benefit at the endpoint level is quantified as ‘minor’, as a moderate improvement is achieved.
• With regard to the other endpoints underlying this benefit assessment – drawn from the categories of mortality, morbidity, health-related quality of life and side effects – there are no further differences in benefit between belatacept and the appropriate comparator therapy.
• With regard to the health-related quality of life endpoints, although there is a statistically significant difference in the physical health summary score in favour of belatacept, the magnitude of the effect does not suggest a clinically relevant difference.
• The 95% confidence interval for this score does not lie entirely above the irrelevance threshold of 0.2 (Hedges’ g), meaning that the additional benefit of belatacept for this endpoint is not proven.
• Overall assessment
  • In its overall assessment of all endpoints, the G-BA summarises the extent of the additional benefit, taking into account the severity of the disease, as ‘minor’.
  • The decisive factor for this assessment is the result at endpoint level for ‘renal insufficiency with CKD stage 4/5’, which demonstrates a moderate improvement in patient-relevant benefit compared with the appropriate comparator therapy, in accordance with Section 5(7) in conjunction with Section 2(3) of the AM-NutzenV.
  • A balancing decision was not required.

Courtesy translation only, please refer to the German original.