Original Title: Avis - Prolastin-C Liquid – Déficit congénital en alpha1-antitrypsine

Authors' objectives: At the request of the manufacturer, Grifols Therapeutics Inc., the Institut national d'excellence en santé et en services sociaux (INESSS) conducted an evaluation of the Prolastin-C, a highly purified human alpha1-proteinase inhibitor administered intravenously. In Canada, Prolastin-C Liquid is indicated for chronic replacement therapy in people with congenital alpha1-proteinase (alpha1-antitrypsin deficiency) related to the PiZZ, PiZ (null), Pi (null)(null), PiSZ genotypes, or any other deficiency allele, and clinically diagnosed emphysema. The intended indication for this evaluation is as follows: for the treatment of alpha1-antitrypsin deficiency related to the PiZZ, PiZ (null), Pi (null)(null), PiSZ genotypes, or any other deficiency allele, in adult patients with clinical emphysema AND an alpha1-antitrypsin level ≤ 11 µmol/L AND FEV1 of 25-80 %. INESSS conducted simultaneous evaluations of Prolastin-C Liquid, Zemaira and Glassia, all human plasma alpha1-antitrypsin products. Recommandations 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 slow progression. Due to the heterogeneous and often delayed clinical manifestations, and 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 sufferers and their families. Facilitating access to augmentation therapy is also desirable. (#2 CLINICAL DIMENSION - EFFICACY): In the EXACTLE exploratory study, Prolastin appeared to reduce emphysema progression compared with placebo in individuals with DAAT. Human plasma AAT products Prolastin, Prolastin-C and Prolastin-C Liquid are considered bioequivalent in individuals with DAAT. (#2.1 CLINICAL DIMENSION - SAFETY): The safety profile of Prolastin observed in the EXACTLE study is considered acceptable. • Although evaluated over shorter periods, the safety profiles of Prolastin-C and Prolastin-C Liquid appear 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 obtain a call for tenders from Héma-Québec before they can be distributed. During this change of management, it would be prudent to avoid treatment interruptions and minimize the consequences that could be associated with them. (#4 ECONOMIC DIMENSION - EFFICIENCY ANALYSIS): When compared to the use of best supportive care alone, Prolastin-C Liquid, in addition to best supportive care, is not cost-effective. The incremental cost-utility ratio was estimated at $327,000 to $337,000 per QALY. A price reduction of 86% or 70% must be adopted to reach efficiency thresholds of $50,000 and $100,000 per QALY, respectively. (#5 SOCIO-CULTURAL DIMENSION): In 2022, Quebec adopted a policy aimed at optimizing access to quality healthcare and services that are adapted to the specific needs of culturally sensitive patients and those with rare diseases. Some experts note that Quebec is at the forefront in the management of 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 slow progression. Due to the heterogeneous and often delayed clinical manifestations, and 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 sufferers and their families. Facilitating access to augmentation therapy is also desirable. (#2 CLINICAL DIMENSION - EFFICACY): In the EXACTLE exploratory study, Prolastin appeared to reduce emphysema progression compared with placebo in individuals with DAAT. Human plasma AAT products Prolastin, Prolastin-C and Prolastin-C Liquid are considered bioequivalent in individuals with DAAT. (#2.1 CLINICAL DIMENSION - SAFETY): The safety profile of Prolastin observed in the EXACTLE study is considered acceptable. • Although evaluated over shorter periods, the safety profiles of Prolastin-C and Prolastin-C Liquid appear 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 obtain a call for tenders from Héma-Québec before they can be distributed. During this change of management, it would be prudent to avoid treatment interruptions and minimize the consequences that could be associated with them. (#4 ECONOMIC DIMENSION - EFFICIENCY ANALYSIS): When compared to the use of best supportive care alone, Prolastin-C Liquid, in addition to best supportive care, is not cost-effective. The incremental cost-utility ratio was estimated at $327,000 to $337,000 per QALY. A price reduction of 86% or 70% must be adopted to reach efficiency thresholds of $50,000 and $100,000 per QALY, respectively. (#5 SOCIO-CULTURAL DIMENSION): In 2022, Quebec adopted a policy aimed at optimizing access to quality healthcare and services that are adapted to the specific needs of culturally sensitive patients and those with rare diseases. Some experts note that Quebec is at the forefront in the management of several rare diseases, including DAAT, compared to other Canadian provinces.

Authors' methods: A data review of the literature and those provided by the manufacturer was carried out to document the efficacy, safety, and cost-effectiveness of Prolastin-C Liquid as well as previous Prolastin and Prolastin-C formulations. Contextual and experiential data from expert consultation are also presented. Efficiency and budget impact analyses were developed by the INESSS.

Project Status: Completed

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

Year Published: 2023

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

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