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Safinamide in Parkinson disease: No hint of added benefit

Relevant study data were not considered / analyses in the dossier were incomplete regarding serious side effects in the comparator therapy, long-term data and other aspects

Institute for Quality and Efficiency in Health Care

Safinamide (trade name: Xadago) has been available since February 2015 as add-on therapy for the treatment of mid- to late-stage Parkinson disease in adults. In combination with levodopa alone or together with other Parkinson disease medicinal products, this monoamine oxidase (MAO-B) inhibitor is used to help restore dopamine levels in the brain. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether this drug offers an added benefit over the appropriate comparator therapy.

Such an added benefit cannot be derived from the dossier, however, because relevant study data were not considered and the analyses were therefore incomplete.

Indirect comparison with limited study pool

Due to a lack of studies of direct comparisons, the drug manufacturer conducted an adjusted indirect comparison with studies that tested either safinamide or the COMT inhibitor entacapone as appropriate comparator therapy against placebo. All six studies included provided data on a 24-week treatment: Two studies provided data on safinamide and four studies on entacapone.

One of the safinamide studies (016) was followed by an extension phase (018), in which the patients were treated for another 78 weeks (total duration 016/018: 102 weeks). The manufacturer did not include this extension phase in the benefit assessment because it did not identify an entacapone study with the same duration. It had limited study selection to the exact duration (24 and 102 weeks). The additionally relevant and more current entacapone study BIA-91067-301 with a treatment duration of 52 weeks was therefore not included in the study pool.

Analyses incomplete because relevant study data were lacking

The limitation of the study pool is methodologically inadequate and resulted in an important loss of information. The analyses in the dossier are therefore incomplete and cannot be used for the assessment of the added benefit: It would be possible to conduct a comparison with the long-term data from the safinamide study 016/018 in connection with the missing entacapone study.

Furthermore, only the BIA-91067-301 study provided information on serious side effects (SAEs) on the entacapone side of the indirect comparison. Moreover, treatment of adults with Parkinson disease has probably changed in the last 5 to 15 years so that the missing study results may be more similar to the safinamide studies from about the same period of time than the four entacapone studies included, all of which were approximately ten years older.

G-BA decides on the extent of added benefit

This dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (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 », published by IQWiG, provides easily understandable German-language information.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on » If you would like to be informed when these documents are available, please send an e-mail to »

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