IQWiG Perampanel without added benefit

IQWiG finds no evidence of added benefit of Perampanel

18/12/2012

The G-BA has appointed the Institute for Quality and Efficiency in Health Care (IQWiG) to evaluate the pharmaceutical active substance perampanel § 35a SGB V instructed. The evaluation was based on a dossier of the pharmaceutical entrepreneur (pU). As a result, there was no added benefit in the benefit assessment of the perampanel-containing antiepileptic Fycompa®.

Since September 2012, the drug has been approved in the pharmaceutical market in Germany. The drug will be used as an adjunct therapy for partial onset seizures with or without secondary generalization in epilepsy patients 12 years of age or older. The G-BA has defined the following ACT: Lamotrigine or, where lamotrigine is used as a monotherapy, topiramate is an adjunct therapy as the ACT.

The pharmaceutical entrepreneur (pU) agrees with the ACT of the G-BA, but with the restriction that topiramate is not considered as an ACT for the derivation of the added benefit of perampanel. The company justified this procedure by stating the G-BA from the consultation, „... a comparison against lamotrigine as a monotherapy is not effective as an adjunct therapy due to the planned field of application for perampanel“. Since topiramate should only be ACT in the specific case in which lamotrigine is used as a monotherapy, a comparison with topiramate is also not effective. This procedure is not followed. The advisability of topiramate as a comparator therapy is given when it is given as adjunctive therapy to a lamotrigine-based basic therapy, provided that perampanel is given as an adjunctive therapy to a lamotrigine-containing basic therapy. The evaluation was thus carried out without restriction to the ACT according to the G-BA.

The company did not include direct comparative studies with perampanel versus lamotrigine. All randomized controlled trials (RCTs) identified with Perampanel are placebo-controlled and are not sufficient to demonstrate an added benefit compared to the ACT. Nevertheless, the company based on this dossier assessment A12-12 Version 1.0 Perampanel - benefit assessment according to § 35a SGB V studies made a direct comparison with a subpopulation of patients who received lamotrigine as part of their basic therapy. Patients taking perampanel in addition to lamotrigine-based baseline therapy will be compared to patients who received placebo in addition to lamotrigine-based baseline therapy. The presented data represent a comparison with placebo and are not suitable to answer the question of the benefit assessment.

The company also conducted an adjusted indirect comparison between perampanel and the ACT lamotrigine as adjunctive therapy. The company chose placebo as a bridge comparator. For Perampanel, in turn, it includes the subpopulation of patients from the 3 placebo-controlled approval studies who received perampanel or placebo in addition to lamotrigine-containing baseline therapy. For lamotrigine, the company included 2 placebo-controlled randomized trials in which lamotrigine or placebo was given in addition to a baseline therapy. Even the indirect comparison is not suitable for answering the question. On the one hand, this is not a comparison of perampanel and lamotrigine as required by the ACT, each as an add-on therapy to a basic therapy. Rather, the combination of perampanel and lamotrigine with lamotrigine, each as an adjunctive therapy compared to a basic therapy of antiepileptic drugs. It should also be noted that patients in the placebo group received lamotrigine as part of their basic therapy in the perampanel studies, which was not the case in the placebo groups in the lamotrigine studies. Thus, the similarity of the bridge comparator is questionable.

The data provided by the company was not relevant for the assessment of the added benefit of perampanel versus the ACT lamotrigine as adjunct therapy. The company did not carry out a comparison of perampanel and topiramate. While conducting an appropriate search for topiramate trials, it presents results for 2 placebo-controlled trials of topiramate, but does not include these in an indirect comparison with perampanel.

For the question of the benefit assessment, there are no relevant data in the dossier, either for a direct comparison or for an indirect comparison with lamotrigine or topiramate. There is thus no proof of an added benefit of perampanel compared to the ACT specified by the G-BA.

Based on the results presented, the extent and the probability of the added benefit of the active substance perampanel from IQWiG are assessed as follows: „Based on available data, there is no evidence of added benefit of perampanel compared to the ACT specified by the G-BA. As a result, there are no patient groups for which a therapeutically significant added benefit can be derived.“ (sb, with material from IQWIG)

Credit: TommyS