Original Title: Avis: Takhzyro (lanadélumab injectable): angiœdème héréditaire, 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) carried out an evaluation of Takhzyro (lanadelumab), a monoclonal antibody for subcutaneous injection every other week (with the option of reducing the frequency to every 4 weeks) that is indicated for the routine prevention of hereditary angioedema (HAE) attacks in adolescents and adults. Takhzyro is not intended for the treatment of acute HAE attacks.

Authors' results and conclusions: RESULTS: (EFFICACY): In terms of the efficacy of the treatment observed during the pivotal study, there was a significant reduction in the monthly attack rate in the order of 73 to 87% compared to placebo during the 26-week treatment period. There was a similar response with regard to moderate and severe attacks and attacks requiring on-demand treatment (0.21-0.42 per month for the lanadelumab groups vs. 1.64 per month for the placebo group). More than half of the lanadelumab-treated patients experienced a greater than 90% attack rate reduction relative to the run-in period. In concrete terms, this clinical response meant 4.3 to 4.7 additional days with no HAE symptoms per 4-week period. No comparative data with plasma-derived C1-INH concentrates are currently available. Quality of evidence: low (SAFETY): Most of the patients in the pivotal study reported adverse events. For the most part, they were mild to moderate in severity and were often injection site reactions. Two transient hypersensitivity reactions were reported, and low titers of antidrug antibodies were detected in approximately 10% of the patients, but they had no apparent impact on the drug’s pharmacokinetic properties or the treatment’s efficacy. Quality of evidence: low (QUALITY OF LIFE) On the whole, in the pivotal study, proportionately more patients in the lanadelumab-treated groups (63.0 to 80.8%) reported a clinically significant improvement in their quality of life than those in the placebo group (36.8%), based on the AE-QoL instrument. The few patients consulted who had tried lanadelumab in a clinical study reported that the treatment had a positive impact on their quality of life. In their opinion, the subcutaneous route of administration and the frequency of injection (every other week) are two important advantages. Quality of evidence: very low (THERAPEUTIC VALUE) The experts consulted consider the clinical results promising. However, some deplored the absence of active comparators (novel mechanism of action), the small size of the groups (variability in the demographic characteristics and clinical efficacy) and the short duration of follow-up (medium- and long-term efficacy and safety). Patients and some of the experts consulted consider the administration of lanadelumab more convenient (route of administration and frequency), but more robust data are needed to demonstrate a significant improvement in quality of life. As well, although the clinical results seem promising, lanadelumab is being marketed in Québec at a time when prophylactic management of HAE is based on an effective physiological treatment (replacement therapy) whose safety is supported by multi-year follow-ups. For these reasons, the members of the Groupe d’experts sur les produits du système du sang consider that the evidence is still too immature to confidently recognize the therapeutic value of lanadelumab.

Authors' recommendations: The members of the Comité scientifique permanent de l’évaluation des médicaments aux fins d’inscription (CSEMI) unanimously refused to recognize the therapeutic value of lanadelumab (Takhzyro) for the systematic prevention of hereditary angioedema (HAE) attacks in adults and adolescents. In light of the available data, INESSS considers that adding lanadelumab (Takhzyro) to the Liste des produits du système du sang du Québec for the systematic prevention of hereditary angioedema attacks (HAE) in adults and adolescents with type 1 or 2 HAE would not constitute a fair and reasonable option. More data are needed to support the introduction of this drug.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/takhzyromc-lanadelumab-injectable-angioedeme-hereditaire-mise-a-jour-de-la-liste-des-produits-du-systeme-de-sang-du-quebec-aout-2020.html

Year Published: 2020

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/takhzyromc-lanadelumab-injectable-angioedeme-hereditaire-mise-a-jour-de-la-liste-des-produits-du-systeme-de-sang-du-quebec-aout-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