Vismodegib has already been approved since 2013 for the treatment of patients with locally advanced basal cell carcinoma (BCC) or symptomatic metastatic BCC and has already undergone an early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG).

The Federal Joint Committee (G-BA) limited its decision in February 2014 to two years, which is why the drug manufacturer now submitted a new dossier.

In its second early benefit assessment, the German Institute for Quality and Efficiency in Health Care (IQWiG) came to the same conclusion as in the first one: The data presented on the drug showed no superiority in comparison with the appropriate comparator therapy.

Hence an added benefit of vismodegib is still not proven.

No better data two years later

The appropriate comparator therapy was best supportive care (BSC), i.e. an individual combination of the best possible supportive treatments.

According to the G-BA, this can also include surgery or radiotherapy for patients with symptomatic metastatic BCC, which is not the case in locally advanced BCC.

As already in the first dossier, the manufacturer presented no data from randomised or non-randomised comparative studies that would be suitable for the assessment of an added benefit of vismodegib for patients with symptomatic metastatic BCC or with locally advanced BCC.

In the newly submitted data from four one-arm intervention studies, patients with symptomatic metastatic BCC cannot be differentiated from study participants with metastases, but without symptoms (metastatic BCC), for example.

Furthermore, study results on the outcome "objective response rate" were not presented adequately for locally advanced BCC patients; there was no information on size, number and location of skin lesions, for example.

Hence the manufacturer did not implement one of the conditions of the G-BA's Limitation.

Manufacturer's assumptions on BSC not justified

Moreover, a simplified search conducted by IQWiG showed that the study pool on locally advanced BCC in the dossier was incomplete.

The manufacturer stated that it had found no studies on BSC, for example.

Besides two further potentially relevant studies, IQWiG identified one study (Horn 2003), however.

This study runs counter to the manufacturer's assumptions that no studies on BSC in patients with locally advanced BCC existed and that it could be assumed that patients with locally advanced BCC do not respond to BSC: In the study, 75 per cent of the patients with locally advanced BCC responded completely after three months; after 24 months, these were still at least 50 per cent.

Furthermore, the manufacturer claimed that nothing was known on the occurrence of adverse events in BSC.

The study Horn 2003 actually addressed this outcome, however: No serious adverse events were reported.

Overall, there was no hint of an added benefit of vismodegib in comparison with the appropriate comparator therapy for any of the two research questions.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to AMNOG supervised by the G-BA.

After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.

An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary.

In addition, the Website gesundheitsinformation.de, published by IQWiG, provides easily understandable German-language information.

More English-language information will be available soon (Sections 2.1 to 2.5 of the dossier assessment as well as subsequently published health information on informedhealth.org).

If you would like to be informed when these documents are available, please send an e-mail to » info@iqwig.de.

Source: Institute For Quality And Efficiency In Health Care