Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Givosiran (akute hepatische Porphyrie, ≥ 12 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: Givlaari® is indicated for the treatment of acute hepatic porphyria (AHP) in adults and adolescents aged 12 years and older. The benefit assessment is based on the pivotal study ENVISION (ALN-AS1-003), a multicentre, multinational, double-blind, phase III study evaluating the efficacy and safety of Givlaari® in adults and adolescents (≥ 12 years) with a documented diagnosis of AHP, including AIP, HCP, PV, or ADP. The study population included 94 patients, stratified by AHP type at baseline and randomised in a 1:1 ratio to the intervention (n=48; 46 with AIP) and placebo group (n=46; 43 with AIP). Patients with AIP were stratified by use of hemin prophylaxis during the screening phase and annual rate of porphyria attacks before study entry. The study was divided into a 2-months screening phase, a 6-months treatment phase, a 29-months extension phase and a one-months follow-up period. Primary objective was the evaluation of the effect of Givlaari® compared to placebo on the annual rate of porphyria attacks requiring hospitalisation in patients with AIP. Deaths were documented within the safety assessment. No patient died during the study. There were statistically significant advantages for Givlaari® over the control group in the number of all porphyria attacks and in the number of porphyria attacks requiring emergency treatment, as well as in PGI-C. No differences occurred between study arms in the number of porphyria attack requiring hospitalisation or administration of hemin at home and overall health status (EQ-5D-VAS) or in pain intensity (BPI-SF item 3), fatigue (BFI item 3) and nausea (NRS). The overall certainty of morbidity results is limited. Results showed a statistically significant benefit for Givlaari® in the SF-36 PCS, while no differences were found for SF-36 MCS. With equal observation times, adverse events occurred numerically in more patients from the intervention vs. control arm. A conclusive assessment of the safety profile was not possible.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/546/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4500/2020-10-15_AM-RL-XII_Givosiran_D-536_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/546/#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/