Benefit assessment requirements should be considered in the early trial planning

Tue, 2018 / 07 / 10

[vc_row][vc_column][vc_column_text]The recent benefit assessments published by the Institute for Quality and Efficiency in Health Care (IQWIG) for the active substances emicizumab and glycopyrronium bromide confirm this position. Emicizumab is a monoclonal antibody approved for routine hemophilia A prophylaxis with Factor VIII inhibitors. Glycopyrronium bromide, on the other hand, is indicated for children and adolescents from 3 years of age with a chronic neurological disease to symptomatically treat the associated severe sialorrhoea (chronic pathologically increased salivation). Although both indications have a great unmet medical need and both products have displayed effectiveness in clinical trials, the manufacturers failed to demonstrate the additional benefit in relation to the comparator therapy defined by the G-BA.

In the case of both drugs, the study design did not take into account the appropriate comparator as established by the G-BA, IQWiG concluded. Accordingly, due to the lack of these data the additional benefit postulated by the developer could not be confirmed by IQWiG. This was the case despite the positive results of the studies conducted and successful marketing approval. In the randomized clinical study of emicizumab (HAVEN 1), the drug was compared with the so-called on-demand treatment rather than routine prophylaxis which is the relevant comparator set by the G-BA. In the case of glycopyrronium bromide, randomized trials compared the therapy only with a placebo. In this case, however, the comparator determined by the G-BA was "Best Supportive Care", a personalized symptomatic treatment of patients, for example through speech therapy or occupational therapy. However, this was not included in the placebo-controlled comparison arms of the clinical trials.

The demonstration of an additional benefit compared to the comparator defined by the G-BA is of central importance for the pricing of the product in Germany. The consequences of an inadequate study design can be far-reaching for the success of a new drug at a national level, depending on the indication and price anchor. However, a low German price can also have significant international implications due to the international price referencing system. This emphasises once again that the requirements of national HTA procedures, especially the early benefit assessment in Germany, must be taken into account early in the study design in order to ensure that the necessary evidence is generated. Conversely, a lack of these considerations can fundamentally jeopardize the commercial potential of an otherwise promising new drug.[/vc_column_text][/vc_column][/vc_row]