Added benefit of lixisenatide is not proven

August 2, 2013, Institute for Quality and Efficiency in Health Care

Lixisenatide (trade name: Lyxumia) has been approved in Germany since February 2013 for the treatment of type 2 diabetes mellitus in combination with oral blood-glucose lowering drugs or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the current standard therapy. No such added benefit can be derived from the dossier, however, because the drug manufacturer did not present any suitable data for any of the possible therapeutic indications of lixisenatide.

G-BA specified appropriate comparator therapy

Lixisenatide is approved in combination with other blood-glucose lowering drugs, including basal insulin. Depending on the type of prior treatment, there are different subindications within the therapeutic indication for the use of lixisenatide, for which the Federal Joint Committee (G-BA) specified different comparator therapies. For the combination of lixisenatide with , sulfonylurea (glibenclamide or ) plus metformin is the appropriate comparator therapy.

Two subpopulations are differentiated for the subindication "lixisenatide plus sulfonylurea" regarding the appropriate comparator therapy: For patients for whom metformin is suitable, the comparison is made with the combination of metformin and sulfonylurea. For patients who do not tolerate metformin, the comparison is made with human insulin. A sulfonylurea may be given in addition to human insulin if this is necessary for the individual patient.

The triple combination of lixisenatide with metformin and sulfonylurea is to be compared with human insulin (if applicable, plus metformin). If lixisenatide is combined with basal insulin with or without metformin, the appropriate comparator therapy specified is also human insulin (if applicable, plus metformin).

Manufacturer deviated from appropriate comparator therapy

In the subindication "lixisenatide plus metformin", the manufacturer additionally defined two specific patient groups, for which it specified comparator therapies deviating from the G-BA. In both cases, the manufacturer did not give sufficient reasons for deviating from the comparator therapy defined by the G-BA.

The manufacturer confined itself to a certain part of the specified comparator therapy in the subindications "lixisenatide plus sulfonylurea" when metformin is unsuitable, and "lixisenatide plus basal insulin (if applicable, plus metformin)": It only made a comparison with basal insulin or with intensified conventional insulin treatment instead of considering all treatment options with human insulin. It therefore also only presented data for this comparison.

The manufacturer compared the triple combination "lixisenatide plus metformin plus sulfonylurea" with basal insulin plus metformin plus sulfonylurea. IQWiG did not accept the reasons given by the manufacturer for the deviation, either, because this treatment option is not advisable from a medical point of view because of more frequent side effects, among other things.

Indirect comparisons unsuitable

The manufacturer did not present a direct comparative study between lixisenatide and the appropriate comparator therapy for any of the four subindications mentioned.

For two subindications, it conducted adjusted indirect comparisons based on several studies. In principle, such indirect comparisons can be suitable to prove an added benefit. The three studies it used for the combination of lixisenatide with metformin were unsuitable, however: In two cases, sulfonylureas were not used according to their approval status, and in one case, the study participants differed considerably from the patients in the lixisenatide study, including with regards to baseline levels, age, and BMI. Hence treatment effects from the indirect comparison could not be interpreted.

As to the combination of lixisenatide and (if applicable, plus metformin), the pharmaceutical company also drew on an adjusted indirect comparison. But the four studies with intermediate comparators were also unsuitable for this comparison because of different patient populations, deviating aims of treatment, and heterogeneous comparator therapies, among other things. Hence the treatment effects could also not be interpreted.

The manufacturer itself did not identify any relevant studies for lixisenatide in dual combination with sulfonylurea versus the appropriate comparator therapy. In the triple combination with metformin plus sulfonylurea, it deviated from the appropriate comparator therapy and did not present any relevant studies.

Hence the dossier did not contain any study results for any of the four therapeutic indications that would be suitable to prove an added benefit.

G-BA decides on the extent of added benefit

The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer's dossier and IQWiG's assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

Explore further: Added benefit of dapagliflozin is not proven

Related Stories

Added benefit of dapagliflozin is not proven

June 6, 2013
Dapagliflozin (trade name: Forxiga) has been approved in Germany since November 2012 for the treatment of type 2 diabetes mellitus. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal ...

Added benefit of saxagliptin/metformin combination is not proven

April 29, 2013
The fixed combination of the drugs saxagliptin and metformin (Komboglyze) has been approved in Germany since November 2011 for the treatment of type 2 diabetes mellitus. In an early benefit assessment pursuant to the "Act ...

Added benefit of linagliptin is not proven

January 6, 2012
Linagliptin (trade name: Trajenta) has been approved since August 2011 to improve blood glucose control ("glycaemic control") in adults with type 2 diabetes mellitus whose elevated blood glucose levels are inadequately controlled ...

Linagliptin: Once again, no proof of added benefit

January 30, 2013
Linagliptin (trade name Trajenta) has been approved since August 2011 to improve blood glucose control in adults with type 2 diabetes. The assessment of the new dossier according to the German Act on the Reform of the Market ...

Added benefit of ingenol mebutate is not proven

June 6, 2013
The drug ingenol mebutate (trade name: Picato) has been approved in Germany since November 2012 as a gel for the treatment of certain forms of actinic keratosis in adults. In an early benefit assessment pursuant to the Act ...

Aflibercept in AMD: No proof of added benefit

June 5, 2013
It is not proven that patients with wet age-related macular degeneration benefit from the new drug aflibercept, as the drug manufacturer did not present any suitable data for a comparison with the current standard therapy ...

Recommended for you

In most surgery patients, length of opioid prescription, number of refills spell highest risk for misuse

January 17, 2018
The possible link between physicians' opioid prescription patterns and subsequent abuse has occupied the attention of a nation in the throes of an opioid crisis looking for ways to stem what experts have dubbed an epidemic. ...

Patients receive most opioids at the doctor's office, not the ER

January 16, 2018
Around the country, state legislatures and hospitals have tightened emergency room prescribing guidelines for opioids to curb the addiction epidemic, but a new USC study shows that approach diverts attention from the main ...

FDA bans use of opioid-containing cough meds by kids

January 12, 2018
(HealthDay)—Trying to put a dent in the ongoing opioid addiction crisis, the U.S. Food and Drug Administration on Thursday slapped strict new restrictions on the use of opioid-containing cold and cough products by kids.

Taking ibuprofen for long periods found to alter human testicular physiology

January 9, 2018
A team of researchers from Denmark and France has found that taking regular doses of the pain reliever ibuprofen over a long period of time can lead to a disorder in men called compensated hypogonadism. In their paper published ...

Nearly one-third of Canadians have used opioids: study

January 9, 2018
Nearly one in three Canadians (29 percent) have used "some form of opioids" in the past five years, according to data released Tuesday as widespread fentanyl overdoses continue to kill.

Growing opioid epidemic forcing more children into foster care

January 8, 2018
The opioid epidemic has become so severe it's considered a national public health emergency. Addiction to prescription painkillers, such as oxycodone and morphine, has contributed to a dramatic rise in overdose deaths and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.