Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Ponatinib (Neubewertung nach Fristablauf: Akute lymphatische Leukämie)

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: Ponatinib is approved for the treatment of adult patients with chronic phase (CP), accelerated phase (AP), or blast phase (BP) chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation and for adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation. The benefit assessment of Ponatinib is based on the pivotal studies PACE and OPTIC. PACE is a completed, single-arm, multicenter, open-label, Phase II study in patients with CML in any phase and Ph+ ALL who were either resistant or intolerant to prior therapy with dasatinib or nilotinib, or who had developed a T315I mutation as a result of TKI therapy. A total of 417 patients with CML and 32 with Ph+ ALL subjects were enrolled in the study and treated with ponatinib 45 mg/day. OPTIC is an ongoing, multicenter, randomized, Phase II study to assess the safety and efficacy of ponatinib at three different starting doses (45 mg, 30 mg, 15 mg) in patients with CP-CML who had received at least two prior TKI therapies and had resistance to prior therapy or had a T315I mutation. Since the recommended starting dose of Ponatinib is 45 mg, only the study arm with a dosage of 45 mg (94 patients) was considered. The bias potential of studies PACE and OPTIC is considered high due to the uncontrolled study design. By the time of analysis, median overall survival had not been achieved for patients with CP-CML. Median overall survival was 241.3 weeks (95% CI: [140.0; n. e.]) for patients with AP-CML, 29.9 weeks (95% CI: [17.0; 40.6]) for patients with BK-CML and 33.1 weeks (95% CI: [19.0; 65.4]) for patients with Ph+ ALL. No morbidity endpoints were considered to be patient-relevant and no data on quality of life were available for the evaluation of ponatinib. Adverse Events (AEs) occurred in all patients and adverse events with a severity level ≥ 3 and serious AEs occurred in almost all patients. The most common serious side effects were pneumonia, pancreatitis, pyrexia, abdominal pain, myocardial infarction, atrial fibrillation, peripheral arterial occlusive disease, anaemia, angina pectoris, decreased blood levels of platelets, febrile neutropenia, hypertension, coronary artery disease, cardiac failure, stroke, sepsis, cellulitis, acute kidney injury, urinary tract infection and increased levels of lipase. Arterial occlusive adverse events occurred in 25% of patients, with serious adverse events occurring in 20% of patients. Serious venous occlusive adverse events occurred in 5% of patients. Because the data are based on single-arm studies, they do not allow comparison of ponatinib versus other TKIs or other therapies.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/556/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4549/2020-11-20_AM-RL-XII_Ponatinib_D-554_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/556/#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/