Empagliflozin (trade name: Jardiance) has actually been approved because Could 2014 for adults along with type 2 diabetes mellitus in whom diet regimen and physical exercise alone do not offer adequate glycaemic control. In 2014, the German Institute for Quality and Efficiency in Good health Care (IQWiG) concluded in its dossier assessment that an added reward of the drug in comparison along with the right comparator therapies was not proven. Partly, the drug manufacturer had presented no relevant data; partly not just the drugs, however likewise the therapeutic strategies differed; in addition, the indirect comparisons were based on studies unsuitable for the assessment.
The manufacturer now requested a brand-new reward assessment as a result of “brand-new scientific findings”, and submitted two dossiers: one for empagliflozin alone, and one for empagliflozin in combination along with metformin. IQWiG determined in the 2 early reward assessments that the dossiers still contained no data and analyses relevant or suitable for the research questions. Hence an added reward of empagliflozin alone or in combination along with metformin in comparison along with the right comparator therapies is still not proven. The analyses of the large study EMPA-REG-Outcome additionally submitted were unsuitable for an assessment of the added reward in Germany.
Same studies, Exact same problems
Both the single agent and the combination of empagliflozin along with metformin are approved alone or in combination along with various other blood-glucose lowering drugs including insulin. According to the Federal Joint Committee (G-BA), this resulted in 3 and four research questions respectively. The manufacturer again presented no relevant data for 5 of these seven research questions so that an added reward is not proven. One study of direct comparison also as several studies for indirect comparisons, every one of which had currently been cited in the dossier or in the commenting procedure in 2014, were readily available for the various other two research questions.
The assessment of the data from the indirect comparison was incomplete along with regard to content, even though it had been known to the manufacturer because the initial dossier assessment which patient-relevant outcomes were important. In particular, there was no write-up on personal side events for which a disadvantage of empagliflozin versus the comparator therapy was shown. The write-up offered on among the indirect comparisons had the Exact same deficiency; furthermore, there were contradictions to the clinical study reports. The second indirect comparison was not evaluable due to the fact that the studies compared were not sufficiently similar and due to the fact that therapeutic strategies rather than drugs were compared along with one an additional again.
Hence there was no hint of an added reward of empagliflozin in comparison along with the right comparator therapies for the single agent or for the fixed combination.
Study EMPA-REG-Outcome unsuitable for the assessment of the added benefit
Both dossiers additionally contained a description of the EMPA-REG-Outcome study used by the manufacturer to answer a question posed by the manufacturer itself, i.e. whether empagliflozin (alone or along with metformin) along with standard treatment offers an added reward for patients at higher cardio risk in comparison along with standard treatment alone plus placebo.
The antidiabetic therapy in this study cannot be considered standard treatment, however: The blood-glucose lowering treatment was not escalated appropriately and the top threshold values specified in guidelines were not consistently respected. And also if treatment was escalated, this was mostly done as emergency treatment, however not as Section of a planned treatment expansion.
Effects in favour of empagliflozin mainly in Latin America and Asia
Moreover, marked local differences were notable: Effects in favour of empagliflozin mainly taken place in study centres in Latin America and Asia, whereas in Europe, partly benefits and partly disadvantages of empagliflozin were shown. Finally, the study addressed neither the G-BA’s research questions nor the right comparator therapies stated there.
Thomas Kaiser, Head of the IQWiG Drug Assessment Department, commented on this attempt by the manufacturer to prove an added reward for at the very least certain patients: “This is a wasted opportunity. It need to be welcomed that studies of this size and this duration, which are therefore potentially informative, are conducted. however it was conducted along with obvious deficiencies. Experts had pinned higher hopes on this study, particularly as, in contrast to various other large outcome studies, it appeared to create positive outcomes at initial glance. A thorough analysis of the study and the outcomes in European participants did not confirm this impression, however.”
G-BA decides on the extent of added benefit
The dossier assessments are Section of the early reward 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 assessments, the G-BA conducts commenting procedures and makes Last decisions on the extent of the added benefit.
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An overview of the outcomes of IQWiG’s reward assessments is provided by German-language executive summaries. In addition, the Website gesundheitsinformation.de, published by IQWiG, provides easily understandable German-language information.
More English-language write-up will certainly be readily available soon (Sections 2.1 to 2.7 and Appendix A of dossier assessment A16-12, and Sections 2.1 to 2.6 of dossier assessment A16-13 also as subsequently published Good health write-up on informedhealth.org). If you would certainly love to be informed once these documents are available, please send an e-mail to » info@iqwig.de.
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