Caplacizumab (Cablivi)

Key Messages

• Canada’s Drug Agency (CDA-AMC) recommends that Cablivi be reimbursed by public drug plans for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP) in combination with plasma exchange (PE) and immunosuppressive therapy (IST), if certain conditions are met.
• CDA-AMC previously reviewed Cablivi in 2020 and 2023, for the treatment of adults with aTTP in combination with PE and IST, and issued a recommendation not to reimburse in both reviews. This is a resubmission based on new information submitted by the sponsor to address the gaps identified in the previous recommendations.
• The Canadian Drug Expert Committee (CDEC) determined that it is uncertain whether Cablivi with PE and IST demonstrates acceptable clinical value versus PE and IST alone in patients with aTTP. Given that Cablivi is expected to be an additive treatment to PE and IST, acceptable clinical value refers to added value versus PE and IST alone.
• Previous CDEC recommendations for Cablivi in 2020 and 2023 concluded that treatment with Cablivi with PE and IST reduced the time for platelet counts to return to normal based on evidence from 1 clinical trial (the HERCULES study; N = 145) and other supportive studies. However, CDEC could not draw conclusions on important outcomes, such as survival, organ damage, preventing new aTTP episodes over long periods of time, use of health care resources, or quality of life. Evidence from a retrospective observational study reviewed for the resubmission (the Capla 1000+ project; N = 1,525) suggested that Cablivi with PE and IST improved survival at 3 months versus PE and IST alone in patients with aTTP. The treatment effect for other important outcomes was consistent across the study in this review and past reviews; however, there was uncertainty because of study limitations. There was also a lack of information for outcomes that are important to patients, such as long-term survival, reduced organ damage, and improved quality of life.
• CDEC determined that there was significant unmet clinical need because aTTP is a severe disease despite treatments being available, and because there is difficulty with conducting clinical studies in aTTP. CDEC determined that Cablivi with PE and IST may address a significant unmet clinical need to a degree that justifies a positive recommendation despite the uncertainty in the clinical value.
• Based on all of the preceding considerations, CDEC recommended that Cablivi be reimbursed.
• Cablivi should only be reimbursed for adults aged 18 years and older experiencing an episode of aTTP, and when used in combination with PE and IST, in line with the Health Canada indication.
• Cablivi should only be reimbursed if the maximum time that Cablivi is used for each aTTP episode is no more than 58 days after the last day that PE is used, and if the cost of Cablivi is reduced. Cablivi should only be prescribed and used by health care specialists who have expertise in managing aTTP and in a clinical setting where PE is provided.