Belatacept (trade name: Nulojix) has been approved since June 2011 for adults after a kidney transplant. It is used together with other drugs to prevent the body from rejecting the transplanted organ. After a first early benefit assessment in April 2012, the German Institute for Quality and Efficiency in Health Care (IQWiG) now reexamined whether the drug offers an added benefit over the appropriate comparator therapy. This new assessment was conducted because a limitation of the corresponding decision by the Federal Joint Commission (G-BA) expired in July 2015.
An indication of considerable added benefit in comparison with ciclosporin A can be derived from the second dossier. Renal insufficiency due to rejection reactions occurs less frequently under belatacept -- and this is the case in all transplanted patients. The first dossier, in contrast, had shown an indication of minor added benefit only in a certain type of donors.
Observation period of seven instead of three years
The company used the same randomized controlled trials in its second dossier as it had done in its first dossier. However, the second dossier contained additional analyses of the data that were already known, and results from later data cut-offs. These now referred to an observation period of seven years; in the first dossier, the observation period considered had only been three years.
Advantage in renal insufficiency
These long-term data showed no relevant differences between the treatment groups regarding mortality. Belatacept had an advantage in renal insufficiency, however: This occurred less frequently in transplanted patients with advanced-stage chronic kidney disease (stage 4/5). IQWiG assessed this as an indication of considerable added benefit. This assessment is independent from the classification of the respective donor.
One study investigated standard criteria donors (SCDs), where the organs come from living donors or from donors deceased after an accident, for example. The other study included patients with extended criteria donors (ECDs). ECD means that only organs from deceased donors are used who also have certain accompanying diseases or who are over 60 years of age.
Standard criteria donors: hint of added benefit in further outcome
If an SCD kidney was used, the 7-year data also showed an advantage of belatacept in the composite outcome "death or graft loss", which IQWiG assessed as a hint of an added benefit. This did not apply to ECDs, however.
Regarding further aspects of symptoms and late complications decisive for patients, such as cardiovascular disease or occurrence of diabetes mellitus, no statistically significant differences between the study arms were shown. The dossier contained no evaluable data for health-related quality of life.
Greater or lesser harm not proven
The advantage of belatacept determined in the first dossier assessment had been based on fewer side effects (serious adverse events) and on fewer treatment discontinuations due to such events. Based on the data that represent the effects over the much longer period of seven years, there were either no relevant group differences for these outcomes, or the data were not evaluable.
The latter applies to treatment discontinuation due to adverse events. The reason is that the data in the dossier did not apply to the total population of the study, but only to a limited population. Greater or lesser harm of belatacept is therefore not proven.
Overall, IQWiG therefore sees an indication of considerable added benefit of belatacept in comparison with ciclosporin A.
G-BA decides on the extent of added benefit
This dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.
An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website » http://www.
More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on » http://www.