Original Title: Arzneimittel-Richtlinie/Anlage XII: Pegcetacoplan (Paroxysmale Nächtliche Hämoglobinurie, vorbehandelte Patienten)

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: Pegcetacoplan is approved for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH) who are anaemic after treatment with a C5 inhibitor for at least 3 months. The benefit assessment is based on the phase 3 study APL2-302 which assessed the efficacy and safety of pegcetacoplan in 80 patients with PNH aged ≥18 years who received eculizumab therapy but continued to have Hb levels under 10.5 g/dL. The study treatment period includes a 4-week run-in period in which all participants were initially treated with a combination therapy of pegcetacoplan and eculizumab, a subsequent 16-week open-label randomized controlled period (RCP) investigating pegcetacoplan monotherapy compared to eculizumab monotherapy, and a 32-week open-label uncontrolled pegcetacoplan extension period. In general, the study design is considered critical because the investigational drug was applied to all study participants before randomization. Furthermore, the effects of pegcetacoplan were not fully captured in the RCP, as only pegcetacoplan monotherapy was investigated in the controlled period. Treatment effects of the combination of pegcetacoplan and eculizumab were only assessed in the uncontrolled run-in period. With respect to the validity of the open-label RCP findings, carry over effects and patient’s experiences from the run-in period may have influenced the results. In the RCP, statistically significant superiority of pegcetacoplan compared to eculizumab was observed for fatigue but not for thrombotic or cardiovascular events. Statistically significant more patients achieved transfusion avoidance during the 16 weeks with pegcetacoplan compared to eculizumab. However, this observation period does not allow a conclusion for longer-term effects. No differences were found between treatments groups in severe and serious adverse events (AE) and AE leading to treatment discontinuation. The results are associated with a high risk of bias.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/812/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5617/2022-09-15_AM-RL-XII_Pegcetacoplan_D-770_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/812/#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/