Narsoplimab Medicine 10 December 2019 Extended indication Treatment of patients with haemopoietic stem cell transplant-associated thrombotic microangiopathy. Therapeutic value No estimate possible yet Total cost Registration phase Registration application pending Product Active substance Narsoplimab Domain Hematology Reason of inclusion New medicine (specialité) Main indication Stem cell transplants Extended indication Treatment of patients with haemopoietic stem cell transplant-associated thrombotic microangiopathy. Current proprietary name Already available biosimilars / generics Proprietary name Manufacturer Omeros Portfolio holder Mechanism of action Complement inhibitor Route of administration Intravenous Therapeutical formulation Injection / infusion Budgetting framework Intermural (MSZ) Centre of expertise Additional remarks Narsoplimab is a human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. The lectin pathway is one of the principal pathways of complement and is activated primarily by tissue damage and microbial infection. Importantly, inhibition of MASP-2 does not appear to interfere with the classical complement pathway, a critical component of the acquired immune response to infection. Registration Registration route Centralised (EMA) Type of trajectory Particularity ATMP No Submission date July 2025 Expected Registration August 2026 Orphan drug Yes Registration phase Registration application pending Reimbursement Medicine sluice Additional remarks In de Verenigde Staten heeft narsoplimab een FDA Breakthrough designation ontvangen. Therapeutic value Current treatment options Therapeutic value No estimate possible yet This assessment does not indicate any potential inclusion in the package. Substantiation Duration of treatment Median 8 week / weeks Frequency of administration 1 times a week Dosage per administration 4mg/kg References - Gavriilaki E, Ho VT, Schwaeble W, et al. Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy. Exp Hematol Oncol. 2021;10(1):57. Published 2021 Dec 19. doi:10.1186/s40164-021-00249-8 - Schoettler M, Chonat S, Williams K, Lehmann L. Emerging therapeutic and preventive approaches to transplant-associated thrombotic microangiopathy. Curr Opin Hematol. 2021;28(6):408-416. doi:10.1097/MOH.0000000000000687 - Young JA, Pallas CR, Knovich MA. Transplant-associated thrombotic microangiopathy: theoretical considerations and a practical approach to an unrefined diagnosis. Bone Marrow Transplant. 2021;56(8):1805-1817. doi:10.1038/s41409-021-01283-0 Additional remarks Wekelijkse intraveneuze infusie, toegediend in een klinische of poliklinische setting. Expected patient volume per year Patient volume < 25 Market share is generally not included unless otherwise stated. Maximum patient volume for sluice References - Postalcioglu M, Kim HT, Obut F, et al. Impact of Thrombotic Microangiopathy on Renal Outcomes and Survival after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018;24(11):2344-2353. doi:10.1016/j.bbmt.2018.05.010 - Arai Y, Yamashita K, Mizugishi K, et al. Serum neutrophil extracellular trap levels predict thrombotic microangiopathy after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19(12):1683-1689. doi:10.1016/j.bbmt.2013.09.005 - Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011;118(6):1452-1462. doi:10.1182/blood-2011-02-321315 Additional remarks Jaarlijks worden in Nederland circa 600 allogene stamceltransplantaties uitgevoerd. De geschatte incidentie van TMA bij deze patiënten ligt rond de 15% (90 patiënten). Het inclusiecriterium van de trial is vanaf 12 jaar. Heel beperkte groep die uiteindelijk in aanmerking zal komen, verwachting is minder dan 25 patiënten op jaarbasis. Expected cost per patient per year Cost References Additional remarks Potential total cost per year Total cost Total cost for sluice Additional remarks Off label use Off label use Yes Indications off label use References - Gavriilaki E, Ho VT, Schwaeble W, et al. Role of the lectin pathway of complement in hematopoietic stem cell transplantation-associated endothelial injury and thrombotic microangiopathy. Exp Hematol Oncol. 2021;10(1):57. Published 2021 Dec 19. doi:10.1186/s40164-021-00249-8 - Rambaldi A, Gritti G, Micò MC, et al. Endothelial injury and thrombotic microangiopathy in COVID-19: Treatment with the lectin-pathway inhibitor narsoplimab. Immunobiology. 2020;225(6):152001. doi:10.1016/j.imbio.2020.152001 Additional remarks Indication extension Indication extensions Yes Indication extensions aHUS; IgA Nephropathy (IgAN); Lupus Nephritis & Other Renal Diseases. References Omeros pipeline. Additional remarks Other information Additional remarks