Original Title: Arzneimittel-Richtlinie/Anlage XII: Burosumab (neues Anwendungsgebiet: X-chromosomale Hypophosphatämie, ≥ 18 Jahre)

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: CRYSVITA is indicated for the treatment of X-linked hypophosphataemia (XLH), in children and adolescents aged 1 to 17 years with radiographic evidence of bone disease, and in adults. The benefit assessment is based on the pivotal study UX023-CL303 (CL303), a randomised, double-blind, placebo-controlled, multicentre phase III study evaluating the efficacy and safety of CRYSVITA in adults with XLH. The study population included 134 patients (aged 18 to 65), 68 in the intervention arm and 66 in the control arm, who were randomised in a 1:1 ratio to CRYSVITA (1.0 mg/kg body weight) or placebo according to two stratification factors average pain in the past 7 days and region. The study consisted of a screening phase, a 24-week blinded, placebo-controlled treatment phase, a continuation phase and an optional extension phase. Primary endpoint was achieving serum phosphate levels above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L]) at mid-dose cycle (i.e., weeks 2, 6, 10, 14, 18, and 22). Deaths were documented during safety recording. No person died during the course of the study. There were statistically significant benefits for CRYSVITA over placebo in the “stiffness” and “physical function” subscales of the WOMAC, yet clinical relevance of these effects is unclear. No significant differences between treatment arms were found for walking distance (6MWT), pain (WOMAC), pain intensity and pain interference (BPI-SF), responder analysis using item 3 of the BPI-SF, the total score of the BFI, and in the PGI-I. Quality of life was not assessed. Only minor differences in the occurrence of adverse events (AE) were observed between study arms, both numerically to the advantage and disadvantage of CRYSVITA. Few serious AE were observed. Clusters occurred only in the PT "dental abscess" and in the UE of special interest "hyperphosphatemia," both to the disadvantage of CRYSVITA. A conclusive assessment of the safety profile was not possible.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/603/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4784/2021-04-15_AM-RL-XII_Burosumab_D-588_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/603/#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/