IQWiG finds no evidence of additional benefits of perampanel
The G-BA commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to evaluate the active pharmaceutical ingredient perampanel in accordance with Section 35a Social Code Book V. The assessment was based on a dossier from the pharmaceutical company (company). As a result, no benefit was found in the benefit assessment of the perampanel-containing antiepileptic agent Fycompa®.
The drug has been approved on the pharmaceutical market in Germany since September 2012. The active pharmaceutical ingredient is to be used as an additional therapy for focal seizures with or without secondary generalization in epilepsy patients from the age of twelve. The G-BA has determined the following appropriate comparator therapy: lamotrigine or in cases where lamotrigine is used as monotherapy, topiramate is the appropriate comparator therapy as additional therapy.
The pharmaceutical company (company) agreed with the appropriate comparator therapy of the G-BA, but with the restriction that topiramate was not considered as an appropriate comparator therapy for deriving the additional benefit from perampanel. The company justified this procedure with the G-BA's finding from the consultation, "... a comparison against lamotrigine as monotherapy was not expedient due to the intended application for perampanel as additional therapy". Since topiramate should only be appropriate comparative therapy in the specific case in which lamotrigine is used as monotherapy, a comparison with topiramate is also not expedient. This is not followed. The usefulness of topiramate as comparison therapy is given when it is administered as an additional therapy to a lamotrigine-containing basic therapy, provided that perampanel is also given as an additional therapy to a lamotrigine-containing basic therapy. The evaluation was therefore carried out without restriction compared to the appropriate comparator therapy according to the G-BA.
The company did not include any directly comparative studies with perampanel versus lamotrigine. All randomized controlled trials (RCTs) identified for Perampanel are placebo-controlled and alone are not sufficient to demonstrate an added benefit compared to the ACT. The company nevertheless conducted a direct comparison with a subpopulation of patients who received lamotrigine as part of their basic therapy based on this dossier assessment A12-12 version 1.0 perampanel - benefit assessment according to § 35a Social Code Book V studies. Patients who received perampanel in addition to basic therapy containing lamotrigine are compared with patients who received placebo in addition to basic therapy containing lamotrigine. The data presented represent a comparison with placebo and are not suitable for answering the question of benefit assessment.
The company continued to perform an adjusted indirect comparison between perampanel and the appropriate comparator therapy lamotrigine as additional therapy. The company chose placebo as the bridge comparator. For Perampanel, it again includes that subpopulation of patients from the 3 placebo-controlled approval studies who received Perampanel or placebo in addition to a basic therapy containing lamotrigine. For lamotrigine, the company included 2 placebo-controlled randomized trials in which lamotrigine or placebo was given in addition to basic therapy. The indirect comparison is also unsuitable for answering the question. On the one hand, it is not a comparison of perampanel and lamotrigine required according to the definition of the appropriate comparative therapy, each as additional therapy to a basic therapy. Rather, the combination of perampanel and lamotrigine with lamotrigine is compared here, each as an additional therapy to a basic therapy made from antiepileptic medication. It should also be noted that in the perampanel studies, patients in the placebo group received lamotrigine as part of their baseline therapy, which was not the case in the placebo groups in the lamotrigine studies. The similarity of the bridge comparator must therefore be questioned.
The data presented by the company were not relevant for the assessment of the additional benefit of perampanel compared to the appropriate comparator therapy lamotrigine as additional therapy. The company did not compare perampanel and topiramate. He does a corresponding search for studies on topiramate and presents results on 2 placebo-controlled studies on topiramate, but does not include these in an indirect comparison with perampanel.
In summary, there are no relevant data in the dossier for the question of benefit assessment, neither for a direct comparison nor for an indirect comparison with lamotrigine or topiramate. There is thus no proof of an additional benefit of perampanel compared to the appropriate comparative therapy determined by the G-BA.
On the basis of the results presented, the extent and the likelihood of the additional benefit of the active ingredient perampanel was assessed by the IQWiG as follows: "From the available data there is no proof of an additional benefit of perampanel in comparison to the appropriate comparative therapy determined by the G-BA. As a result, there are no patient groups for whom a therapeutically significant additional benefit can be derived. ”(Sb, with material from IQWIG)
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