Original Title: Avis : RebinynMC, Facteur IX de coagulation (recombinant) – Nonacog bêta pégol, avis d’introduction à la Liste des produits du système du sang du Québec

Authors' objectives: The Institut national d’excellence en santé et en services sociaux (INESSS) evaluated the blood system product RebinynTM (nonacog beta pegol), an intravenously injected recombinant factor IX (FIX) indicated in adults and children with hemophilia B (congenital factor IX deficiency or Christmas disease) for the control and prevention of bleeding episodes and in the perioperative setting as well as in patients 18 years and above with hemophilia B for routine prophylaxis to prevent or reduce the frequency of bleeding episodes. The following four recombinant FIX, currently indicated for the treatment of hemophilia B and listed in the Liste des produits du système du sang du Québec, served as comparators: BeneFIXTM (nonacog alfa), RixubisTM (nonacog gamma), AlprolixTM (eftrenonacog alfa) et IdelvionTM (albutrepenonacog alfa).

Authors' results and conclusions: RESULTS: (EFFICACY) - The efficacy evaluation for nonacog beta pegol was based on four phase III, open-label and non-controlled trials. As a result of the restriction of the indication, efficacy results for the prophylactic use of nonacog beta pegol in children and adolescents under 18 years f age were not considered. The overall efficacy evidence was considered very low. The prophylactic dose of 40 IU/kg every seven days showed lower median and mean annual bleeding rates compared to the 10 IU/kg dose. The majority of bleeding events satisfied the hemostatic efficacy criteria and most of them required a single injection of nonacog beta pegol. Only one severe bleeding event was treated with nonacog beta pegol. The hemostatic efficacy of the 34 surgeries for which efficacy results were available was considered good or excellent. (SAFETY) - The safety of nonacog beta pegol was evaluated across six clinical studies. A total of 115 unique patients received at least one injection of nonacog beta pegol. The evidence level for the safety results was considered very low. PEG accumulation in the choroid plexus and vacuolation of epithelial cells of the choroid plexus were observed in animals during preclinical trials. The most frequent adverse events observed during the clinical trials were injection site reaction (observed in 3.5 % of subjects) and pruritus (2.6 %). A single case of hypersensitivity reaction was reported and led to the subject’s withdrawal. No subject developed anti-FIX antibodies. (IMPACT OF THE DRUG ON PATIENTS' QUALITY OF LIFE) - Quality of life improvement was found by the HAEMO-QOL-III and HAEM-A-QOL surveys for individuals treated weekly with the 40 IU/kg dose (“feeling” and “sport” domains) and people treated on-demand (“view” domain). CONCLUSIONS: The experts consulted consider that the hemostatic efficacy of nonacog beta pegol, for the requested indications, is considered similar to its recombinant FIX comparators. While some experts mentioned the impossibility of evaluating the efficacy of nonacog beta pegol to treat severe bleedings, others indicated that the overall efficacy evidence is enough to conclude that the product is similar to its comparators. According to the experts consulted, the safety profile of nonacog beta pegol during the clinical trials is considered comparable to its recombinant FIX comparators. Nonetheless, PEG accumulation in the brain of animals during the preclinical trials was considered a considerable risk and some experts mentioned they would not recommend nonacog beta pegol for children.

Authors' recommendations: In light of the available data, INESSS recommends that RebinynTM (nonacog beta pegol) not be added to the Liste des produits du système du sang du Québec since the product’s therapeutic value has not demonstrated. Additional efficacy and safety data with a higher level of evidence are required to support the therapeutic value for the proposed indications.

Authors' methods: EVALUATION PROCESS: Published trials and manufacturer data were reviewed to document the efficacy, safety and efficiency of nonacog beta pegol. Experiential and contextual data from expert consultations and patients are presented as well. HEALTH NEED: Hemophilia B is an X chromosome-linked recessive genetic disease characterized by coagulation factor IX (FIX) deficiency. This deficiency prolongs coagulation times, which can lead to frequent bleeding episodes in the joints (hemarthrosis), muscles and mucus membranes. Some bleeding events can also lead to severe motor handicaps or even be life-threatening. The current FIX replacement therapies enable Quebecers who are type B hemophiliacs to prevent or stop their bleeding episodes. Experts and patients were queried about health needs in the hemophilia B community. Treatments that better prevent the development of inhibitors, hemophiliac arthropathies and chronic pain, and therapies that provide superior, longer-lasting hemostatic protection with fewer intravenous injections were among the needs mentioned most frequently.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/rebinynmc-mise-a-jour-de-la-liste-des-produits-du-systeme-du-sang-du-quebec-juin-2020.html

Year Published: 2020

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/rebinynmc-mise-a-jour-de-la-liste-des-produits-du-systeme-du-sang-du-quebec-juin-2020.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