Extended indication Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) also known as tr
Therapeutic value No estimate possible yet
Registration phase Clinical trials

Product

Active substance Narsoplimab
Domain Hematology
Reason of inclusion New medicine (specialité)
Main indication Stem cell transplants
Extended indication Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) also known as transplant-associated thrombotic microangiopathy (TA-TMA).
Manufacturer Omeros
Mechanism of action Complement inhibitor
Route of administration Intravenous
Therapeutical formulation Injection / infusion
Budgetting framework Intermural (MSZ)
Additional comments 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)
ATMP No
Submission date May 2023
Expected Registration June 2024
Orphan drug Yes
Registration phase Clinical trials
Additional comments In de Verenigde Staten heeft narsoplimab een FDA Breakthrough designation ontvangen. De FDA heeft in 2021 echter aangegeven dat het meer data nodig heeft om de effectiviteit te beoordelen. De ontwikkeling zal daarom vertraagd zijn.

Therapeutic value

Therapeutic value No estimate possible yet
Duration of treatment Median 8 week / weeks
Frequency of administration 1 times a week
Dosage per administration 4 mg/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 comments Weekly intravenous infusion, delivered in an inpatient or outpatient setting

Expected patient volume per year

Patient volume

< 25

Market share is generally not included unless otherwise stated.

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 comments 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

There is currently nothing known about the expected cost.

Potential total cost per year

There is currently nothing known about the possible total cost.

Off label use

Off label use Yes
Indications off label use COVID-19
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

Indication extension

Indication extension Yes
Indication extensions aHUS; IgA Nephropathy (IgAN); Lupus Nephritis & Other Renal Diseases.
References Omeros pipeline.

Other information

There is currently no futher information available.