Original Title: Avis: Glassia – Déficit congénital en alpha1-antitrypsine

Authors' objectives: At the request of the manufacturer, Takeda Canada Inc., the Institut national d'excellence en santé et en services sociaux (INESSS) assessed Glassia, a human alpha1- proteinase inhibitor. In Canada, Glassia is indicated for chronic augmentation and maintenance therapy in adults with clinically evident emphysema due to severe hereditary deficiency of alpha1-PI, also known as alpha1- antitrypsin deficiency. The indication requested from INESSS was the same. INESSS conducted simultaneous assessments of Prolastin-C Liquid, Zemaira and Glassia, all human plasma alpha1-antitrypsin products. Recommendations for these 3 products were published at the same time.

Authors' results and conclusions: RESULTS (#1 POPULATION DIMENSION) Alpha1-proteinase inhibitor deficiency, or alpha1-antitrypsin deficiency (DAAT), is a rare genetic condition with variable presentation that can lead to severe pulmonary (emphysema, chronic bronchitis, and bronchiectasis) and hepatic symptoms, often with a slow progression. Due to the heterogeneous and often delayed clinical manifestations as well as the discovery of new pathogenic variants associated with the disease, DAAT is an under-diagnosed condition. Usual treatments are aimed at alleviating respiratory symptoms and include inhaled medications, pulmonary rehabilitation and, for some patients, augmentation therapy consisting of weekly intravenous administration of plasma-derived alpha1-antitrypsin (AAT). Augmentation therapy aims to slow the progression of emphysema in individuals with DAAT. Currently, only ProlastinTM-C is available in Quebec, and public reimbursement is possible only through the “mesure du patient d’exception”. Treatments that halt or slow the progression of emphysema and the deterioration of lung and liver function would meet current healthcare needs, especially if they were to improve the quality of life of affected individuals and their families. Facilitating access to augmentation therapy is also desired. (#2 CLINICAL DIMENSION - EFFICACY): In individuals with DAAT, the human plasma ATT GlassiaTM product is considered bioequivalent to ProlastinTM since it has a comparable pharmacokinetic profile. • No data on the ability of GlassiaTM to slow the progression of emphysema in individuals with DAAT have been submitted by the manufacturer or reported in the literature. (#2 CLINICAL DIMENSION - SAFETY): The safety profile of Glassia is considered acceptable and comparable to that of Prolastin. (#3 ORGANIZATIONAL DIMENSION): Coverage for human plasma AATs is currently provided by the RAMQ through the mesure du patient d’exception and private insurance plans. From now on, plasma AATs will have to be registered on the Liste des produits du système du sang du Québec and win a tender by Héma-Québec before they can be distributed. During this management change, it would be prudent to avoid treatment interruptions and minimize the consequences that could be associated with them. (#4 ECONOMIC DIMENSION): Should GlassiaTM be added to the Liste des produits du système du sang du Québec, an increase in the number of patients can be expected due to patients currently using ProlastinTM-C through the private drug insurance plan to continue their AAT inhibitor treatment through the public plan. (#5 SOCIO-CULTURAL DIMENSION): In 2022, Quebec adopted a policy aimed at optimizing access to quality health care and services that are adapted to the specific needs of culturally sensitive patients with rare diseases. Some experts recognize that Quebec is at the forefront of care for several rare diseases, including DAAT, compared to other Canadian provinces.

Authors' recommendations: RESULTS (#1 POPULATION DIMENSION) Alpha1-proteinase inhibitor deficiency, or alpha1-antitrypsin deficiency (DAAT), is a rare genetic condition with variable presentation that can lead to severe pulmonary (emphysema, chronic bronchitis, and bronchiectasis) and hepatic symptoms, often with a slow progression. Due to the heterogeneous and often delayed clinical manifestations as well as the discovery of new pathogenic variants associated with the disease, DAAT is an under-diagnosed condition. Usual treatments are aimed at alleviating respiratory symptoms and include inhaled medications, pulmonary rehabilitation and, for some patients, augmentation therapy consisting of weekly intravenous administration of plasma-derived alpha1-antitrypsin (AAT). Augmentation therapy aims to slow the progression of emphysema in individuals with DAAT. Currently, only ProlastinTM-C is available in Quebec, and public reimbursement is possible only through the “mesure du patient d’exception”. Treatments that halt or slow the progression of emphysema and the deterioration of lung and liver function would meet current healthcare needs, especially if they were to improve the quality of life of affected individuals and their families. Facilitating access to augmentation therapy is also desired. (#2 CLINICAL DIMENSION - EFFICACY): In individuals with DAAT, the human plasma ATT GlassiaTM product is considered bioequivalent to ProlastinTM since it has a comparable pharmacokinetic profile. • No data on the ability of GlassiaTM to slow the progression of emphysema in individuals with DAAT have been submitted by the manufacturer or reported in the literature. (#2 CLINICAL DIMENSION - SAFETY): The safety profile of Glassia is considered acceptable and comparable to that of Prolastin. (#3 ORGANIZATIONAL DIMENSION): Coverage for human plasma AATs is currently provided by the RAMQ through the mesure du patient d’exception and private insurance plans. From now on, plasma AATs will have to be registered on the Liste des produits du système du sang du Québec and win a tender by Héma-Québec before they can be distributed. During this management change, it would be prudent to avoid treatment interruptions and minimize the consequences that could be associated with them. (#4 ECONOMIC DIMENSION): Should GlassiaTM be added to the Liste des produits du système du sang du Québec, an increase in the number of patients can be expected due to patients currently using ProlastinTM-C through the private drug insurance plan to continue their AAT inhibitor treatment through the public plan. (#5 SOCIO-CULTURAL DIMENSION): In 2022, Quebec adopted a policy aimed at optimizing access to quality health care and services that are adapted to the specific needs of culturally sensitive patients with rare diseases. Some experts recognize that Quebec is at the forefront of care for several rare diseases, including DAAT, compared to other Canadian provinces.

Authors' methods: A review of data from the literature and those provided by the manufacturer was conducted to document the efficacy, safety, and cost-effectiveness of GlassiaTM. In addition, contextual and experiential data from expert consultation were mobilized and integrated. Efficiency and budget impact analyses were developed by INESSS.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/glassiamc-deficit-congenital-en-alpha1-antitrypsine.html

Year Published: 2023

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/glassiamc-deficit-congenital-en-alpha1-antitrypsine.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

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: L'Institut national d'excellence en sante et en services sociaux (INESSS)