Original Title: Arzneimittel-Richtlinie/Anlage XII: Sebelipase alfa (Neubewertung nach Fristablauf: Mangel an lysosomaler saurer Lipase)

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: Sebelipase alfa (SA) is indicated for long-term enzyme replacement therapy in patients of all ages with lysosomal acid lipase (LAL) deficiency. The benefit assessment is based on the evaluation of intervention studies and one multi-center registry study ALX-LALD-501. For patients <6 months old assessment was based on LAL-CL03 (multicenter, open-label, single-arm study in 9 patients <24 months of age and growth failure with onset <6 months of age) and LAL-CL08 (multicenter, open-label study in 10 infants ≤8 months of age with rapidly progressive LAL deficiency). A comparison, based on external controls, showed a benefit for SA for mortality. Limitations were present due to immortal time bias, non-adjusted indirect comparison, limitations in the comparability of the patient populations and small sample size. Intra-individual comparisons showed an improvement in anthropometric parameters over time compared to baseline. Adverse events (AE) occurred in both groups. In pediatric and adult patients with non-rapidly progressive LAL-deficiency, the benefit assessment was based on LAL-CL06 (phase 2, open-label, single-arm, multicenter study for up to 144 weeks, N=31) and LAL-CL02 (phase 3, double-blind, placebo-controlled, multicenter study for 20 weeks + open-label extension for up to 234 weeks). No deaths occurred until end of both studies. Results were comparable for fatigue and quality of life endpoints between SA (N=36) and placebo (N=30) at week 20 and were comparable to baseline by the end of extension phase (LAL-CL02). Intra-individual comparison showed small increase in anthropometric parameters over time compared to baseline (LAL-CL06). AE were observed in both studies and were comparable by the end of week 20 between treatments arms in LAL-CL02. In ALX-LALD-501, AE occurred in less subjects than in the intervention studies for both indications. Risk of bias was low for the double-blind phase of LAL-CL02 and high for its extension phase and single-arm studies.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/629/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4860/2021-06-03_AM-RL-XII_Sebelipase-alfa_D-606_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/629/#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/