Added benefit of ingenol mebutate is not proven

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 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 diclofenac/hyaluronic acid gel. Such an added benefit cannot be derived from the dossier, however, as the drug manufacturer did not submit any relevant data: it did not cite any studies that directly compared ingenol mebutate with diclofenac/hyaluronic acid gel, and the method chosen by the manufacturer for an indirect comparison was unsuitable.

G-BA specified appropriate comparator therapy

Ingenol mebutate is approved for the treatment of flat, non-callous . These are called non-hyperkeratotic and non-hypertrophic actinic keratoses. This disease can develop into a form of (). The Federal Joint Committee (G-BA) specified diclofenac/hyaluronic acid gel as appropriate comparator therapy.

No direct comparative studies available

In its dossier, the manufacturer did not cite any (RCTs) that directly compared ingenol mebutate gel with diclofenac/hyaluronic acid gel. It therefore aimed for an indirect comparison. However, in the opinion of the manufacturer it was not possible to use a procedure appropriate for this, namely an adjusted indirect comparison with a common point of reference (intermediate comparator). It stated that the substances called vehicle gels that ingenol mebutate and /hyaluronic acid were compared with in the available studies might differ in efficacy, and are therefore not comparable. These substances could therefore not be used as intermediate comparator.

Method of analysis unsuitable for indirect comparison

Instead, the pharmaceutical company used a method it called "chaining of direct comparisons". In such a comparison across several comparators it is indispensable, however, that direct comparisons exist for each link in the chain, i.e. for each pair of comparators. This condition was not fulfilled, however, as the manufacturer presented a non-adjusted comparison for one link in the chain. Hence the method of analysis was unsuitable, and its results could therefore not be used. An added benefit of ingenol mebutate is therefore not proven.

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.

add to favorites email to friend print save as pdf

Related Stories

Aflibercept in AMD: No proof of added benefit

Jun 05, 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 ...

Perampanel for epilepsy: No proof of added benefit

Jan 30, 2013

The drug perampanel (trade name Fycompa) has been approved since July 2012 as adjunctive ("add-on") therapy for adults and children aged 12 years and older with epileptic fits (seizures). In an early benefit assessment according ...

Added benefit of fampridine is not proven

Aug 29, 2012

Fampridine (trade name Fampyra) has been approved in Germany since July 2011 for adult patients suffering from a higher grade walking disability (grades 4 to 7 on the EDSS disability status scale), as a result of multiple ...

Added benefit of aclidinium bromide is not proven

Jan 30, 2013

The drug aclidinium bromide (trade names Eklira, Bretaris) has been approved since October 2012 for widening the narrowed airways of adults with chronic-obstructive pulmonary disease (COPD). The German Institute for Quality ...

Recommended for you

Cancer: Tumors absorb sugar for mobility

1 hour ago

Cancer cells are gluttons. We have long known that they monopolize large amounts of sugar. More recently, it became clear that some tumor cells are also characterized by a series of features such as mobility or unlikeliness ...

Early hormone therapy may be safe for women's hearts

11 hours ago

(HealthDay)—Healthy women at low risk of cardiovascular disease may be able to take hormone replacement therapy soon after menopause for a short time without harming their hearts, according to a new study.

Low yield for repeat colonoscopy in some patients

11 hours ago

(HealthDay)—Repeat colonoscopies within 10 years are of little benefit to patients who had no polyps found on adequate examination; however, repeat colonoscopies do benefit patients when the baseline examination was compromised, ...

Cell's recycling center implicated in division decisions

14 hours ago

Most cells do not divide unless there is enough oxygen present to support their offspring, but certain cancer cells and other cell types circumvent this rule. Researchers at The Johns Hopkins University have now identified ...

User comments