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 sclerosis (MS). The German Institute for Quality and Efficiency in Health Care (IQWiG) has assessed the added benefit of the drug pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG). According to the findings, there is no proof of added benefit, as the manufacturer's dossier contains no evaluable study data for the comparison between fampridine and the appropriate comparator therapy.
G-BA specifies physiotherapy as the appropriate comparator therapy
MS is a chronic incurable inflammatory disease, in which the patient's own immune system damages nerve tracts in the brain and spinal cord. In some patients, some muscles are in permanent spasm or are paralysed. If the disease is more advanced, patients may develop a walking disability.
The Federal Joint Committee (G-BA) has specified physiotherapy as the appropriate comparator therapy for the benefit assessment. This treatment must fulfil the requirements of the German Guideline on Remedies (Heilmittelrichtlinie). In addition, the patients must receive optimized standard therapy for MS.
Requirements for an indirect comparison not fulfilled
There are no studies that directly compare fampridine with physiotherapy. Instead, the pharmaceutical company presented data on an indirect comparison. These data originate from studies in which fampridine was compared with a placebo or in which physiotherapy was compared with "no treatment".
The legal ordinance on AMNOG explicitly specifies that it is possible to prove added benefit using indirect comparisons too. However, specific methodological conditions apply, which were not fulfilled by the manufacturer in the fampridine dossier.
Marked differences in the grade of disability
In addition, the studies on physiotherapy which the pharmaceutical company has evaluated cannot be used, as they also included patients with a markedly lower grade of disability (EDSS from 1.5) than in the studies on fampridine. Thus, the populations were not similar enough to allow a comparison between the results.
Finally, the manufacturer does not discuss in the dossier whether the physiotherapy tested in these studies was in accordance with the criteria of the Guideline on Remedies and, if this is not the case, why these studies would nevertheless allow conclusions about the situation in Germany. Moreover, the manufacturer does not mention whether the patients actually received optimized MS standard therapy. However, these two points are conditions specified by the G-BA for the appropriate comparator therapy.
Hence the manufacturer did not present evaluable studies on the appropriate comparator therapy for the assessment of the added benefit of fampridine, thereby also failing to present an evaluable indirect comparison. Thus there is no proof of added benefit of fampridine.
G-BA decides on the extent of added benefit.
The dossier assessment is part of the overall procedure for early benefit assessment conducted by the G-BA. After publication of the manufacturer's dossier and its assessment by IQWiG, the G-BA initiates a formal commenting procedure which provides further information and can 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.