Dimethylfumarat (1) – Tecfidera®

Relapsing-remitting multiple sclerosis (MS)

Characteristics

Start date 01.05.2014
Resolution 16.10.2014
INN Dimethylfumarat
Brand name Tecfidera®
Pharm. company Biogen Idec GmbH
G-BA Procedure ID D-100
ATC code L04AX07 Other immunosuppressants (L04AX)
ICD-10 codes (AIS) G35.10, G35.11, G35.9
Alpha-ID codes (AIS) I98549Multiple sclerosis with predominantly relapsing-remitting course, I99339Multiple sclerosis
DDD 0.36 g O
Therapeutic area Nervous system diseases Multiple sclerosis (MS) / Neuromyelitis optica spectrum disorders (NMOSD)
Reason for procedure Initial assessment
Specialty Patent/data protection expired

Therapeutic indication of the resolution

Tecfidera is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis

Subpopulation Indication Comparator
Adult patients with relapsing-remitting multiple sclerosis Interferon beta-1a or interferon beta-1b or glatiramer acetate

Studies and Results

No. of studies
(best subpopulation)
2 (DEFINE, CONFIRM)
Study design
(best subpopulation)
H2H vs. non-ACT + ITC (MTC)
Meta analysis
(best subpopulation)
yes

  • Clinical trials
    • In addition, the G-BA noted that the study 109MS302 (CONFIRM), submitted by the pharmaceutical company, included not only two study arms with different dimethyl fumarate administration frequencies and daily doses, and a placebo control arm, but also an active-controlled arm comparing the drug with glatiramer acetate.

Patients with relapsing-remitting multiple sclerosis (RRMS)

  • An additional benefit compared with interferon beta-1a is not proven.
  • Due to the aforementioned shortcomings regarding completeness, the inadequate verification of the basic assumptions of the network meta-analysis concerning similarity, homogeneity and consistency, and the unsuitable statistical model, the indirect comparison presented in the dossier did not allow for any valid conclusions to be drawn regarding the additional benefit of dimethyl fumarate compared with the selected appropriate comparator therapy, IFN β-1a.
  • mortality
    • The information on deaths (1 death in the IFN β-1a group), also contained in the study report for the MSCRG trial, was not taken into account by the pharmaceutical manufacturer within the indirect comparison of dimethyl fumarate with IFN β-1a.
  • morbidity
    • In the network meta-analysis from the statement, for most endpoints only the comparison of dimethyl fumarate and IFN β-1a, 44 μg s.c. (Rebif®), is considered, which means that this indirect comparison is also substantively incomplete.
  • Side effects
    • Furthermore, no analyses of serious adverse events are presented, and only incomplete analyses of deaths are provided.
  • Overall assessment
    • Due to the differences mentioned above, it cannot be assumed that the study populations included in the indirect comparison are sufficiently similar. Consequently, no valid conclusions regarding the additional benefit of dimethyl fumarate compared with the appropriate comparator therapy can be drawn on the basis of the presented network meta-analysis.
    • Consequently, the results from the presented network meta-analysis cannot be relied upon, as they are also based on an unsuitable statistical model and incomplete analyses.

Courtesy translation only, please refer to the German original.

Associated procedures

Dimethylfumarat (2) Tecfidera® Biogen GmbH Nervous system diseases Relapsing-remitting multiple sclerosis (MS) (new indication: children and adolescents aged 13 years and older)) 350–1,200 100% additional benefit not proven
Dimethylfumarat (1) Tecfidera® Biogen Idec GmbH Nervous system diseases Relapsing-remitting multiple sclerosis (MS) 85,000–105,000 100% additional benefit not proven


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