Original Title: Avis: HemlibraMC (émicizumab) – Hémophilie A

Authors' objectives: The Institut national d’excellence en santé et en services sociaux (INESSS) evaluated emicizumab (Hemlibra™), a bispecific monoclonal antibody indicated for hemophilia A (congenital factor VIII deficiency) patient with or without factor VIII inhibitors as routine prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes. Emicizumab was previously evaluated by INESSS and is listed on the Liste des produits du système du sang du Québec for the following indication: routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients of all ages with hemophilia A (congenital factor VIII deficiency) with factor VIII (FVIII) inhibitors. The recombinant FVIIIs Advate™, Adynovate™, Eloctate™, Kovaltry™, Nuwiq™, Xyntha™ (including Xyntha Solofuse™) and Zonovate™, all of which are listed on the Liste des produits du système du sang du Québec, were used as comparators. Nuwiq™ and Zonovate™ are currently distributed by Héma-Québec, and Eloctate™ is available under an MSSS directive.

Authors' results and conclusions: EVALUATION PROCESS: Data from literature and provided by the manufacturer were reviewed to document the efficacy and safety of emicizumab. Experiential and contextual data from expert and patient consultations are also presented. HEALTH NEEDS: Hemophilia A, caused by FVIII deficiency, manifests as longer-than-normal clotting times. In severe cases, FVIII deficiency leads to frequent bleeding episodes in joints (hemarthrosis) and soft tissues in the absence of trauma. Prophylaxis with plasma-derived or recombinant FVIII is the preferred treatment. Prophylaxis consists of several weekly or even daily intravenous injections to replace the missing FVIII. In some patients, daily doses of FVIII will be administered to achieve treatment goals. Prophylactic treatment therefore imposes a considerable burden on certain patients and their families. In addition, venous access problems may require the use of a central venous access device, a situation that is particularly common among young children (up to about 12 years of age) and obese individuals. These devices cause discomfort and carry an increased risk of infection and thrombosis in these populations. In adult patients who have not received preventive treatment since childhood, polyarthropathy is a source of pain and disability that has a significant impact on their quality of life. PATIENT PERSPECTIVE: Some of the persons living with hemophilia A who have been consulted report difficulties administering the current treatment, which may affect their adherence to the treatment. Some patients and family members indicated that therapeutic compliance is a source of stress and anxiety. Patients also mentioned that frequent visits to a hemophilia centre or a hospital and missed days of work or school are major irritants that affect their quality of life. While a number of respondents expressed satisfaction with their current treatment (FVIII prophylaxis), they expressed a desire for a treatment with a longer half-life, better protection and a simpler, less invasive route of administration. EFFICACY: Available data show that emicizumab prophylaxis at doses of 1.5 mg/kg per week and 3.0 mg/kg every 2 weeks could reduce annualized bleeding rates by 96% and 97%, respectively, compared to no prophylaxis (low level of evidence). However, in Quebec, patient management is based on well-established FVIII prophylaxis. An intra-patient comparison based on a non-randomized and non-interventional design reported that emicizumab prophylaxis (weekly dose of 1.5 mg/kg) reduced the annualized bleeding rate by 68% compared to FVIII prophylaxis. The risk of bias is very high. Some of the experts consulted pointed out that the bleeding rates observed during FVIII prophylaxis were higher than those observed in real-world care settings in Québec, which calls into question the external validity of these results (very low level of evidence). SAFETY: The most common adverse reactions (≥ 1%) observed in clinical studies were injection site reaction (21%), joint pain (16%), headache (14%), fever (6%), diarrhea (5%) and muscle pain (4%). Ever since the warning was issued concerning the use of high doses of activated prothrombin complex concentrate (aPCC) for the treatment of breakthrough bleeding in patients treated with emicizumab, no thrombotic events have been reported. QUALITY OF LIFE: The available data on FVIII prophylaxis is insufficient to determine the impact of emicizumab on quality of life.

Authors' recommendations: In light of the available data, INESSS recommends that Hemlibra™(emicizumab) should not be offered as a treatment option for patients with hemophilia A without factor VIII (FVIII) inhibitors. Additional data are required to support the therapeutic value for the proposed indication. The members of the Comité scientifique permanent de l’évaluation des médicaments aux fins d’inscription (CSEMI) are unanimously of the opinion that the therapeutic value of Hemlibra™ (emicizumab) as routine prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes for hemophilia A (congenital factor VIII deficiency) patients without inhibitors has not been demonstrated.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/hemlibramc-mise-a-jour-de-la-liste-des-produits-du-systeme-du-sang-du-quebec-decembre-2019.html

Year Published: 2019

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/hemlibramc-mise-a-jour-de-la-liste-des-produits-du-systeme-du-sang-du-quebec-decembre-2019.html

Requestor: Minister of Health

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec