Original Title: Arzneimittel-Richtlinie/Anlage XII: Avacopan (Granulomatose mit Polyangiitis oder mikroskopische Polyangiitis, Kombination mit Rituximab oder Cyclophosphamid)

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: Avacopan (Tavneos®) is indicated in combination with a rituximab or a cyclophosphamide dosing regimen for the treatment of adult patients with severe active GPA or MPA. The benefit assessment of Avacopan (Tavneos®) is based on the pivotal ADVOCATE study. This is a randomized, double-blind, multicenter, controlled, parallel-group Phase III study in which patients with either newly diagnosed or relapsed GPA or MPA were randomized 1:1 and stratified by background therapy factors (RTX i. v. vs. CYC i. v./oral), "ANCA specificity" (MPO vs. PR3), and "AAV status" (newly diagnosed vs. recurrent) were assigned to treatment with avacopan (n = 166) or treatment with prednisone (n = 165), each in combination with CYC (i. v. or oral) followed by AZA or MMF, or with RTX (i. v.). Deaths were collected as part of the safety record. By week 60, 2 (1%) deaths occurred in the avacopan arm and 4 (2%) deaths occurred in the prednisone arm. While there was no statistically significant difference between the two study arms for the endpoints "remission" and "health status" (EQ-5D-VAS) at 26 weeks, there was a statistically significant difference to the benefit of avacopan for the endpoints "sustained remission" and "health status" (EQ-5D-VAS) at week 52. The clinical relevance of the effect cannot be assessed for the endpoint "health status" at week 52 based on the SMD in the form of Hedges' g determined by the company. The results for the 3 listed endpoints of the endpoint category "morbidity" are assessed as potentially low biased. For the MCS of the SF-36, there were no statistically significant differences between study arms at week 26 and week 52, but for the PCS, there were differences at both week 26 and week 52 to the advantage of avacopan. The clinical relevance of the effect cannot be assessed for the PCS of the SF-36 at week 26 and week 52 based on the SMD in the form of Hedges' g determined by the company. The results for the endpoint "health-related quality of life" (SF-36) are considered to be potentially low biased. For overall rates of SUEs and UEs leading to discontinuation of study medication, there were no statistically significant differences between study arms. For UE, there was a statistically significant difference to the benefit of avacopan compared with prednisone for each of SOC "Ocular disorders," "Benign, malignant, and nonspecific neoplasms (including cysts and polyps)," and "Endocrine disorders." Severe AEs (grade ≥ 3) occurred numerically more frequently in the prednisone arm. The company did not provide effect estimates with 95% CI and p-values for severe AEs. For SUE, there were no statistically significant differences between study arms at the SOC and PT level, based on p-values from the chi-square test. The potential for bias is assessed as "unclear" for the results of the listed endpoints of the category "safety", as no stratified analyses were provided by the company, despite a stratified randomization.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/798/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5572/2022-08-04_AM-RL-XII_Avacopan_D-778_EN.pdf

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/798/#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/