Original Title: Avis: Alphanate – Maladie de von Willebrand

Authors' objectives: MANDATE: The Institut national d’excellence en santé et en services sociaux (INESSS) carried out an evaluation of Alphanate, an intravenously injected vWF/FVIII concentrate for the prevention and treatment of mild and/or non-life-threatening bleeding episodes or surgical bleeding in adults and pediatric patients with von Willebrand disease (vWD), when desmopressin (DDAVP) is known or suspected to be either ineffective or contraindicated. Alphanate is not indicated for patients with severe vWD (type 3) undergoing major surgery. EVALUATION PROCESS: Literature data and data provided by the manufacturer were reviewed to document the efficacy, safety and efficiency of Alphanate. Experiential and contextual data from expert consultations are presented as well. HEALTH NEED: vWD is the most common hereditary bleeding disorder. It is characterized by a primary deficiency of vW factor (vWF) with or without a secondary deficiency of FVIII. The disease is classified into types 1, 2 and 3, based on the reduced levels and functional activity of vWF. The location and severity of the bleeding varies considerably according to the type of vWD. The bleeding can be mucocutaneous or affect deep tissues, such as joints and muscles, and can lead to tissue destruction or permanent sequelae. Management is based on the normalization of vWF and FVIII during bleeding episodes, perioperative prophylaxis and long-term prophylaxis. In Québec, first-line treatment consists of the intravenous administration of an analogue of the antidiuretic hormone vasopressin, DDAVP, which is generally used to prevent or treat mild to moderate bleeding. In cases of more severe vWD, or when DDAVP is ineffective or contraindicated, replacement therapy with a vWF/FVIII plasma concentrate is administered intravenously. In Québec, it is estimated that approximately 600 patients have vWD, with the following breakdown: 540 type 1, 40 type 2 and 20 type 3. Most patients respond to DDAVP. Otherwise, the plasma-derived vWF/FVIII concentrate Humate-P, which is on the Liste des produits du système du sang du Québec, effectively treats all types of bleeding. Wilate is another vWF/FVIII concentrate figuring on this list, but it is not currently distributed.

Authors' results and conclusions: EFFICACY: Two clinical studies were selected: a prospective pivotal study and a retrospective study. Most of the bleeding episodes (80%) in the pivotal study were completely controlled with one or two injections of Alphanate, in the absence of use of cryoprecipitates, alternate vWF/FVIII concentrate, or platelet infusion. In the prevention of bleeding in a surgical or invasive procedure context, most of surgical procedures (88.7%) in the pivotal study did not generate intraoperative blood loss greater than 1.5 times the predicted value, and 93.5% of surgeries in the retrospective study had a hemostatic response rated as "excellent/good". Out of 132 evaluated procedures (combined results of the pivotal and the retrospective study), 11 surgeries/invasive procedures had a clinical response below expectations and required blood transfusions in some cases to achieve hemostasis. A total of 18 pediatric patients were evaluated in the pivotal study. According to Health Canada, the observed results were comparable to those for adult patients. Quality of evidence: very low SAFETY: No serious treatment-related adverse events, deaths or study discontinuations were observed in the two studies evaluated. The pediatric population evaluated is considered small. A larger pediatric population should be studied. Quality of evidence: very low QUALITY OF LIFE: No study evaluating the impact of Alphanate™ on quality of life was identified. THERAPEUTIC VALUE: Given the available clinical results, and in the absence of comparative studies, the experts consulted believe that Alphanate has a clinical efficacy equivalent to that of the other plasma-derived products Humate-P and Wilate. However, most of these experts maintain that the restriction of Alphanate to cases of minor or non-life-threatening bleeding imposed by Health Canada, is a major handicap, as these needs are already being met with DDAVP. Alphanate is therefore being marketed in a context where Humate-P is already meeting all the needs in the management of vWD when DDAVP is ineffective or contraindicated, and this, in a wide range of clinical scenarios. The Groupe d’experts sur les produits du système du sang concluded that, although Alphanate has a potentially similar clinical profile to Humate-P™ and Wilate™, there is no role for it in the current therapeutic strategy in Québec.

Authors' recommendations: In the light of the available data, INESSS does not consider it relevant to add Alphanate to the Liste des produits du système du sang du Québec for the prevention and treatment of mild and/or non-life-threatening bleeding episodes or surgical bleeding in adults and pediatric patients with von Willebrand disease, when desmopressin (DDAVP) is known or suspected to be either ineffective or contraindicated. The indication for Alphanate is too limited to grant it a role in the current therapeutic strategy in Québec.

Project Status: Completed

Year Published: 2019

URL for published report: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Produits_sanguins/Septembre_2019/INESSS_Alphanate_Avis.pdf

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