Original Title: Avis: KamRAB – Prophylaxie postexposition passive et transitoire contre la rage

Authors' objectives: At the request of the manufacturer, Kamada Ltd., the Institut national d’excellence en santé et en services sociaux (INESSS) evaluated KamRAB™, a human rabies immunoglobulin (HRIG). This product is indicated” for passive, transient postexposure prophylaxis (PEP) of rabies infection, when given immediately after contact with a rabid or possibly rabid animal. KamRAB should be administered concurrently with a full course of rabies vaccine”.

Authors' results and conclusions: RESULTS (#1 POPULATIONAL DIMENSION): Rabies is an infectious disease caused by a virus transmitted from animals to humans. Although the onset of symptoms ends in death in most cases, only 12 deaths have been reported in Quebec since 1924. PEP constitutes the standard of care for reducing the risk of infection by the rabies virus in individuals exposed to an infected or possibly infected animal. PEP includes a full vaccination course and the administration of HRIG to reduce the risk of infection until the vaccine takes full effect. In Québec, a clinical algorithm is used to facilitate patient management and guide clinicians in their decision-making. The algorithm indicates whether the exposure to the virus is significant and whether PEP is recommended, based mainly on the type of animal and the risk associated with the geographical area. Currently, two vaccines and at least one HRIG (HyperRAB™) are available for initiating PEP in patients exposed to the rabies virus. HyperRAB™ is on the Liste des produits du système du sang du Québec. Another HRIG, Imogam™, is not used clinically but is available in the event of a supply problem. Apart from the risk of HRIG shortage, which is low, the health need of individuals exposed or possibly exposed to the rabies virus is adequately met. (#2 CLINICAL DIMENSION): The main efficacy and safety data on the HRIG KamRAB™ come from the phase II/III, randomized, double-blind, comparative, non-inferiority, pivotal study with individuals with no exposure to the rabies virus. This study is considered to be of good methodological quality. The results of a phase IV, single-arm observational study in a rabies-exposed pediatric population were evaluated as well. (#2.1 Efficacy) • The results of the pivotal study show that the PEP protocol including the HRIG KamRAB™ is non-inferior to that using the HRIG HyperRAB™ in inducing protective humoural immunity against the rabies virus. • The pharmacokinetic results and the absence of infection reported in the phase IV study support the conclusion of non-inferiority. (#2.2 Safety) • The safety profile of KamRAB™ is considered satisfactory and similar to that of the comparator HyperRAB™. • The results of the phase IV study show that the safety profile of the HRIG KamRAB™ in children under 16 years of age is comparable to that observed in adults. (#2.3 Expert perspective) • In the experts’ opinion, the two studies selected are adequate for evaluating the non-inferiority of the HRIG KamRAB™ as part of PEP. • They feel that the reported efficacy and safety results for KamRAB™ are similar to those for the comparator HyperRAB™. (#3 ORGANIZATIONAL DIMENSION): Expert perspective • With the products currently available in Québec, listing and distributing KamRAB™ would not have an impact on the quality of care and services provided to individuals exposed to the rabies virus. • According to the experts consulted, adding KamRAB™ to the Liste des produits du système du sang du Québec could alleviate potential HRIG shortages. (#4 ECOMONIC DIMENSION): Cost-effectiveness analysis • At the price submitted, KamRAB™ costs almost twice as much as its comparator, HyperRAB™. On the basis of efficacy and safety considered non-inferior to those of its comparator, KamRAB™ is not considered cost-effective. Budget impact analysis • If KamRAB™ wins the Héma-Québec call for tenders, its inclusion on the Liste des produits du système du sang du Québec could either have no budget impact or result in savings for the healthcare system. This will depend on which product wins the call for tenders.

Authors' recommendations: The members of the Comité scientifique de l’évaluation des médicaments aux fins d’inscription (CSEMI) unanimously agree that the HRIG KamRAB™ should be added to the Liste des produits du système du sang du Québec for concurrent use with vaccination for the passive, transient postexposure prophylaxis of rabies, when administered immediately after contact with a rabid or possibly rabid animal. Reasons for the unanimous position  The members recognize the non-inferior therapeutic value of the HRIG KamRAB™ relative to HyperRAB™ when used concurrently with vaccination in the context of rabies PEP.  All the dimensions considered, the members feel that KamRAB™ constitutes a therapeutic alternative with a non-incremental value relative to the other currently available HRIGs.  The members believe that adding KamRAB™ to the Liste des produits du système du sang du Québec could address potential HRIG shortages, although they acknowledge that the risk is low.  The members are of the opinion that, in a call-for-tenders context, adding KamRAB™ to the Liste des produits du système du sang du Québec could generate savings for the healthcare system. INESSS’s recommendation regarding KamRAB™ In light of the available data, INESSS recommends that the HRIG KamRAB™ be added to the Liste des produits du système du sang du Québec for concurrent use with vaccination for the passive, transient postexposure prophylaxis of rabies in individuals exposed or possibly exposed to the virus. Note concerning the recommendation From a distributive justice perspective, coverage of KamRAB™ for the requested indication would be a responsible, fair and equitable decision, provided the cost of using it does not exceed the cost of the other HRIGs in the next call for tenders.

Authors' methods: Data from the scientific literature and those provided by the manufacturer were reviewed to document the efficacy, safety and cost-effectiveness of KamRAB™. In addition, experiential and contextual data from expert consultations were mobilized and integrated. Lastly, INESSS performed a cost-effectiveness and budget impact analysis.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/kamrabmc-prophylaxie-postexposition-passive-et-transitoire-contre-la-rage.html

Year Published: 2022

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/kamrabmc-prophylaxie-postexposition-passive-et-transitoire-contre-la-rage.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: Gouvernement du Québec