Additional benefit of lixisenatide not used

Lixisenatide is approved for the treatment of diabetes mellitus type second IQWiG has now checks whether this new drug compared with the previous standard therapy offers an additional benefit.

Lixisenatide (Lyxumia ®) has been approved in February 2013, when these do not provide adequate along with diet and exercise increased blood sugar levels for the treatment of type 2 diabetes mellitus in combination with oral hypoglycaemic agents or basal insulin. The Institute for Quality and Efficiency in Health Care (IQWiG) has reviewed an early benefit assessment pursuant pharmaceutical market Restructuring Act (AMNOG) whether this new drug compared with the previous standard therapy offers an additional benefit. However, from the dossier, such an additional benefit can not be inferred because the manufacturer has submitted data suitable for any of the possible applications of lixisenatide.



G-BA determines appropriate comparator therapy
Lixisenatide is approved in combination with other anti-diabetic medicines, including basal insulin. Depending on the type of treatment arising within the area of ​​different indications for the use of lixisenatide for which the Federal Joint Committee (G-BA) has defined each different comparison therapies. For the combination of metformin with sulfonylurea is lixisenatide (glibenclamide or glimepiride) and metformin therapy, the appropriate comparator. In the indication "lixisenatide plus sulfonylurea" are terms of appropriate comparator therapy two subpopulations distinguished: is suitable for patients for whom metformin is compared with the combination of metformin and sulfonylurea. For patients who can not tolerate metformin, compared with human insulin. Unless individually necessary and a sulfonylurea, in addition to human insulin.

The triple combination of lixisenatide with metformin and sulfonylurea is for comparison with human insulin (possibly plus metformin). If lixisenatide combination with basal insulin with or without metformin, human insulin is also (possibly plus metformin) as the appropriate comparator therapy.

Manufacturer differs from suitably comparative therapy
In the indication "lixisenatide plus metformin" defined by the manufacturer in addition two special populations, for which he may determine by the G-BA comparing different therapies. In both cases, the manufacturer has not sufficiently justified its deviation from the specified comparator therapy.

In the indications "lixisenatide plus sulfonylurea" when metformin is not suitable, and "(possibly plus metformin) lixisenatide plus basal insulin", the manufacturer restricted to one specific part of the established comparator treatment: Instead of all treatment options to consider with human insulin, it compares only with basal insulin or with intensified conventional insulin therapy. So he sets only for this comparison before each data.

The triple combination "lixisenatide plus metformin plus sulfonylurea" compares the manufacturer with basal insulin plus metformin plus sulfonylurea. Even this justification for the deviation of the manufacturer does not follow the IQWiG. Because this alternative treatment is medically others because of frequent side effects do not make sense.

Indirect comparisons unsuitable
The manufacturer shall, according IQWiG for any of the four indications mentioned a direct comparative study between lixisenatide and the appropriate comparator therapy before.

For two indications he performs adjusted indirect comparisons based on several studies. Such indirect comparisons may be suitable in principle to impose an additional benefit. The three studies that he employs a combination of lixisenatide with metformin, but are not suitable: In two cases, sulfonylureas were not applied to authorization in accordance with, and in one case, the study participants differed significantly from the patients in the lixisenatide study, including in terms of blood glucose levels at baseline, the age and BMI. Therefore, the treatment effects from the indirect comparison can not interpret.

Also for the combination of lixisenatide with basal insulin (possibly plus metformin) the pharmaceutical company to endorse an adjusted indirect comparison. But the four studies with Brückenkomparatoren are also unsuitable for this comparison, eg due to different patient populations, differing treatment goals and inconsistent comparison therapies. Again, therefore, the treatment effects were not interpretable.

For lixisenatide in dual combination with a sulfonylurea, the manufacturer identifies itself no relevant studies to the appropriate comparator therapy. In the triple combination with metformin plus sulfonylurea, he deviates from the appropriate comparator therapy and presents no relevant studies. Thus, the dossier contains for any of the four indications study results that would be appropriate to impose an additional benefit.