Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Osilodrostat (endogenes Cushing-Syndrom)

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: Osilodrostat (Isturisa) is indicated for the treatment of endogenous Cushing’s syndrome (CD) in adults. The benefit assessment is based on the pivotal study C2301, a multicentre phase III study consisting of an 8-week randomised, double-blind period in a randomised-withdrawal design followed by a 24-week single-arm, open-label treatment period to investigate the efficacy and safety of osilodrostat in CD. Based on the data, no conclusion could be drawn regarding the effects of osilodrostat on mortality in CD. The descriptively reported improvements on the EQ-5D-VAS, a measure of health status, and the BDI-II, a measure of severity of depression, compared to baseline did not allow valid conclusions on a reduction of symptomatology in CD due to missing controls. Regarding quality of life, uncontrolled data showed improvement in the subscales and total score of the CushingQoL over the course of the study compared to baseline, yet no conclusive assessment of quality of life was possible. There were no statistically significant differences in the occurrence of AE between the groups. A comparative assessment of long-term safety was not possible due to the short treatment duration of 8 weeks. In an amendment of the benefit assessment, placebo-controlled data of a further study (study C2302) were considered. Study C2302 is a multicentre phase III study consisting of a 12-week randomised, double-blind, placebo-controlled period, followed by a 36-week open-label, uncontrolled treatment period to investigate osilodrostat in CD. After the 12-week treatment, no statistically significant differences were observed in health status and quality of life between the groups. A statistically significant inferiority of osilodrostat was reported for the BDI-II, but the clinical relevance of this finding is uncertain. There are no statistically significant differences between the groups with regard to severe and serious AEs, and AEs that led to treatment discontinuation.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/568/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4652/2021-01-07_AM-RL-XII_Osilodrostat_D-573_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/568/#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/