Original Title: Arzneimittel-Richtlinie/Anlage XII: Efgartigimod alfa (Myasthenia gravis, AChR-Antikörper+)

Authors' objectives: The Federal Joint Committee [Gemeinsamer Bundesausschuss (G-BA)] has had the legal task of carrying out an (additional) benefit assessment for all newly approved drugs with new active ingredients immediately after market entry (§ 35a SGB V). The result of this assessment is the basis for deciding how much the statutory health insurance pays for a new drug with a new active ingredient. The G-BA was commissioned to carry out the benefit assessment through the Pharmaceuticals Market Reorganisation Act [Gesetz zur Neuordnung des Arzneimittelmarktes (AMNOG)]. In the context of the early benefit assessment of medicinal products containing new active substances, the following rules apply to orphan drugs: According to the legal requirements (§ 35a SGB V), the additional medical benefit of these drugs is already considered to be proven by the approval. The G-BA determines the extent of the additional benefit for orphan drugs that do not exceed a turnover of 50 million Euros in the last twelve calendar months, on the basis of the approval and the studies justifying the approval.

Authors' results and conclusions: Efgartigimod alfa is approved for the treatment of generalized myasthenia gravis in adult patients who are AChR-AK positive, in addition to standard therapy. The benefit assessment of efgartigimod alfa is based on the pivotal ADAPT study, a randomized, multicenter, placebo-controlled phase III trial to evaluate the safety and efficacy of efgartigimod alfa compared with placebo in addition to standard therapy. Only the results for AChR-AK-positive patients are relevant for the benefit assessment. Deaths were documented as part of the safety assessment. During the course of the study ADAPT, no person died. Overall, responder analyses of MG-ADL and EQ-5D-5L-VAS show benefits in favor of efgartigimod alfa for the 1st treatment cycle. However, no stratification factors were included in the analyses resulting in an unclear risk of bias. Due to uncertainties in the selection of the analysis population, only the 1st treatment cycle can be considered in the benefit assessment, which is why statements for further treatment cycles are not possible. Furthermore, the post-hoc endpoint with an improvement of the MG-ADL score by at least 4 points is a one-time improvement. Evidence of efficacy in terms of response over more than one survey time point were submitted during the commenting procedure "proportion of subjects with an improvement in MG-ADL score (≥ 4 points over at least 4 weeks)". There was a statistically significant benefit in favor of efgartigimod alfa for the MG-ADL with an improvement of ≥ 4 points over at least 4 weeks. With the demonstrated advantage in favor of efgartigimod alfa in the AUC evaluation presented post hoc, an overall advantage for efgartigimod alfa in morbidity over 20 weeks can be inferred. Overall, responder analysis of MG-QoL15r shows advantages in favor of efgartigimod alfa for the 1st treatment cycle. Overall, UE and SUE were observed that could include events from the morbidity category. However, there were no differences between treatment arms for UE, SUE, or UE of special interest. The recording of symptoms of the underlying disease, together with possible bias (more frequent visits within a treatment cycle) and possible shortened collection at early end of the study from day 127, due to the need of a new treatment cycle, make conclusive interpretation of the data impossible. Uncertainties about whether stratification factors were considered in the analyses are secondary to this.

Authors' recommendations: Efgartigimod alfa is approved for the treatment of generalized myasthenia gravis in adult patients who are AChR-AK positive, in addition to standard therapy. The benefit assessment of efgartigimod alfa is based on the pivotal ADAPT study, a randomized, multicenter, placebo-controlled phase III trial to evaluate the safety and efficacy of efgartigimod alfa compared with placebo in addition to standard therapy. Only the results for AChR-AK-positive patients are relevant for the benefit assessment. Deaths were documented as part of the safety assessment. During the course of the study ADAPT, no person died. Overall, responder analyses of MG-ADL and EQ-5D-5L-VAS show benefits in favor of efgartigimod alfa for the 1st treatment cycle. However, no stratification factors were included in the analyses resulting in an unclear risk of bias. Due to uncertainties in the selection of the analysis population, only the 1st treatment cycle can be considered in the benefit assessment, which is why statements for further treatment cycles are not possible. Furthermore, the post-hoc endpoint with an improvement of the MG-ADL score by at least 4 points is a one-time improvement. Evidence of efficacy in terms of response over more than one survey time point were submitted during the commenting procedure "proportion of subjects with an improvement in MG-ADL score (≥ 4 points over at least 4 weeks)". There was a statistically significant benefit in favor of efgartigimod alfa for the MG-ADL with an improvement of ≥ 4 points over at least 4 weeks. With the demonstrated advantage in favor of efgartigimod alfa in the AUC evaluation presented post hoc, an overall advantage for efgartigimod alfa in morbidity over 20 weeks can be inferred. Overall, responder analysis of MG-QoL15r shows advantages in favor of efgartigimod alfa for the 1st treatment cycle. Overall, UE and SUE were observed that could include events from the morbidity category. However, there were no differences between treatment arms for UE, SUE, or UE of special interest. The recording of symptoms of the underlying disease, together with possible bias (more frequent visits within a treatment cycle) and possible shortened collection at early end of the study from day 127, due to the need of a new treatment cycle, make conclusive interpretation of the data impossible. Uncertainties about whether stratification factors were considered in the analyses are secondary to this.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/871/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-5876/2023-02-16_AM-RL-XII_Efgartigimod-alfa_D-858_EN.pdf

Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/871/#nutzenbewertung

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Germany

Organisation Name: The Federal Joint Committee

Contact Address: Gutenbergstr. 13, 10587 Berlin, Germany

Contact Name: Fachberatung Medizin [Department of Medical Consultancy]

Contact Email: Fachberatung-Medizin@g-ba.de

Copyright: https://www.g-ba.de/sys/impressum/