Monthly Case

A 23-year-old female patient with learning difficulties suffers from partial epilepsy with complex-partial and secondary generalized tonic clonic seizures since early childhood. So far, she was treated with nine different antiepileptic drugs in high doses without beeing seizure-free, this patient’s epilepsy is pharmacoresistant. High-resolution brain MRI did not detect any lesions. In pre-surgical monitoring with scalp EEG recordings, a right hemispheric seizure onset was seen. However, the epileptogenic zone which was aimed to be resected could not be defined. We recommended to the patient and her family invasive EEG recordings with subdural grid electrodes. Similar to other patients, at first the family was unable to decide for the surgical approach. As the patient still suffered from 4 to 5 complex partial seizures per month, we initiated treatment with perampanel in addition to other antiepileptic drugs. With a daily dose of 8 mg, the patient is seizure-free now for 3 years.

In randomized placebo-controlled trials on antiepileptic drugs, only 4 to 8 % of patients become seizure-free, and the duration of such trials commonly is limited to 3 months. But the primary endpoint of these trials is the responder rate, i.e. the fraction of patients with a reduction in seizure frequency as compared to baseline of at least 50 %. Commonly, 30 to 40 % of patients in the verum arm are responders. Prerequisite for approval by the European Medicine Agency (EMA) in London is a significantly higher responder rate in the group of patients treated with the new anticonvulsant compared to the placebo group. This primary endpoint was successfully met by perampanel, and the drug was introduced into the market.

In Germany, in 2011 a law passed the parliament which aims to re-organized the market of pharmaceutical drugs. In addition to the randomized controlled trials as described above and beyond approval by the EMA, the pharmaceutical companies have to prove that the new drug has an additional benefit in comparison to already available drugs. The companies are required to compare the new compound not to placebo but – in a head-to-head fashion – to “older” antiepileptic drugs which are already EMA-approved. These data are not available from international randomized controlled trials, as most study participations were already treated with the comparator in the long course of their epilepsy and therefore can not be included into the studies. On the basis of this law, the German authorities denied an additional benefit of perampanel compared to other anticonvulsants. The pharmaceutical company which produces perampanel has provided the substance for free in the last 2 years. In spring 2016, perampanel will be withdrawn from the German market.

How to explain to the above reported patient, who is seizure-free with perampanel for more than 3 years and who did not have to undergo epilepsy surgery, that the substance has been declared not to have an additional benefit? In this case, this is difficult to place. We now will ask this patient’s and other successfully treated patients’ health insurance company to pay for the costs of this drug when purchased via international pharmacies. Our patient with learning difficulties will definitely not be able to bear the costs on her own.

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