Efgartigimod alfa (2) – Vyvgart®

• Clinical trials
  • The ADAPT study was a multicentre, double-blind, randomised controlled trial lasting 26 weeks, in which the efficacy and safety of efgartigimod alfa were compared with placebo – in each case in combination with standard therapy.
  • The CHAMPION trial is a randomised, controlled, double-blind Phase 3 trial in which ravulizumab was compared with placebo – in each case, where appropriate, in addition to existing standard therapy – over a period of 26 weeks.
  • The REGAIN study is a randomised, controlled, double-blind, Phase 3 study in which eculizumab was compared with placebo – in each case, where appropriate, in addition to standard treatment – over 26 weeks.

Adults with anti-AChR antibody-positive generalised myasthenia gravis who are eligible for add-on treatment to standard therapy

• For adults with anti-AChR antibody-positive generalised myasthenia gravis who are eligible for add-on treatment to standard therapy, additional benefit is not proven.
• As there are no direct comparative studies of efgartigimod alfa versus eculizumab or ravulizumab, the pharmaceutical manufacturer presents two adjusted indirect comparisons according to Bucher in the dossier, using placebo as the bridge comparator.
• The ADAPT study is not comparable with the CHAMPION and REGAIN studies due to its patient-specific, cyclical treatment regimen combined with the early transition of patients to the ADAPT+ extension study, which were designed for continuous treatment at fixed dosing intervals and monitoring of response at week 26.
• Early transition to the ADAPT+ study occurred if a new treatment cycle could not be completed within the planned study duration of 26 weeks. As a result, the median duration of follow-up in the ADAPT study is only 20 weeks. By contrast, the duration of follow-up in the comparator arm was 26 weeks.
• Particularly in light of the differences in study design – namely, treatment in cycles and, consequently, a highly fluctuating response over the course of the ADAPT study, as opposed to continuous treatment in the CHAMPION and REGAIN studies – it cannot be inferred from these differences in median follow-up durations that there is sufficient similarity between the studies in the two indirect comparisons.
• Furthermore, it cannot be assumed that there is sufficient similarity between the patient populations included in the studies on both the intervention and control sides.
• Overall, the indirect comparisons submitted by the pharmaceutical manufacturer are therefore not suitable for assessing the additional benefit of efgartigimod alfa compared with the appropriate comparator therapy.
• Overall assessment
  • On balance, the indirect comparisons submitted by the pharmaceutical manufacturer are therefore not suitable for assessing the additional benefit of efgartigimod alfa compared with the appropriate comparator therapy. For adults with anti-AChR antibody-positive gMG who are eligible for adjunctive treatment alongside standard therapy, the additional benefit of efgartigimod alfa is therefore not proven.

Courtesy translation only, please refer to the German original.