Koate –DVI (double viral inactivation solvent treated human factor VIII) / Grifols, Kedrion - LARVOL DELTA

Caplacizumab Treatment, without Plasma Exchange, of a Jehovah's Witness with Thrombotic Thrombocytopenia Purpura Resulted in Rapid and Durable Remission: A Case Report (ASH 2022) - "The patient and family refused, due to religious convictions (Jehovah Witness) against receiving "any of the 4 blood products": RBC, WBC, platelets, or plasma.She did agree to treatment according to Chander, et al, NEJM 381(1) 2019: pp 92-94: caplacizumab 11 mg subcutaneously daily x 30 days, prednisone 1 mg/kg x 14 days, then tapered over 7 days, rituximab 375 mg/m2 day 1, 8, 15, and 22, and Koate-DVI (a human plasma derived factor VIII concentrate that contains ADAMTS13) 3 days a week for 2 weeks.This treatment was well tolerated, with no unusual or unexpected toxicities, except for minor bruising around the SQ caplacizumab injection sites...She is being maintained on low dose aspirin and followed carefully for relapse.TTP is caused by depletion of ADAMTS13, leading to accumulation of very large vWF multimers, which causes thrombotic microangiopathy from platelet aggregation and consumption...James George and Spero Cataland that additional successful outcomes..."

Clinical • Anorexia • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • HP

Low-dose immune tolerance induction therapy in children of Arab descent with severe haemophilia A, high inhibitor titres and poor prognostic factors for immune tolerance induction treatment success. (PubMed, Haemophilia) - "A low-dose ITI therapy using a pdFVIII/VWF concentrate achieved at least partial tolerance in 80% of patients, and reduced annual bleeds in children with high inhibitor titres and at least one poor prognosis factor for ITI treatment success."

Biomarker • Clinical • Journal • Hematological Disorders • Hemophilia • Rare Diseases

RESIST EXP: Rescue Immunotolerance Study in Induction of Immune Tolerance (ITI)-Experienced Patients (RES.I.S.T. Experienced) (clinicaltrials.gov) - P=N/A; N=3; Completed; Sponsor: City of Hope Medical Center; Active, not recruiting ➔ Completed; Trial completion date: Jun 2020 ➔ Oct 2020; Trial primary completion date: Jun 2020 ➔ Oct 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Rare Diseases

RESIST NAIVE: Study of First TIME Immunotolerance Induction in Severe Hemophilia A Patients With Inhibitor at High Risk of Failure: Comparison With FVIII Concentrates With or Without Von Willebrand Factor - RES.I.S.T. Naive (clinicaltrials.gov) - P=N/A; N=0; Withdrawn; Sponsor: City of Hope Medical Center; N=148 ➔ 0; Active, not recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Hematological Disorders • Hemophilia • Rare Diseases

Hereditary Thrombotic Thrombocytopenic Purpura in a 9-Month Old: Diagnosing and Managing an Ultra-rare Disorder. (PubMed, J Pediatr Hematol Oncol) - "Genetic testing revealed one known pathogenic mutation and one novel mutation of ADAMTS13 classified as likely pathogenic on the basis of parental genetic testing and in silico analyses. We further discuss off-label use of prophylactic plasma-derived Factor VIII (Koate-DVI) and the benefit of rare disease registries."

Journal • Hematological Disorders • Rare Diseases • Thrombocytopenia • Thrombocytopenic Purpura

Kedrion Biopharma receives FDA approval to package Koāte double viral inactivation (DVI) antihemophilic factor (human) with Mix2Vialneedle-free transfer device (Businesswire) - "Kedrion Biopharma has gained approval from the U.S. Food and Drug Administration to package Koāte® Double Viral Inactivation (DVI) Antihemophilic Factor (human) with Mix2Vial™, a needle-free transfer device. The new packaging is designed to offer hemophilia patients optimized safety and convenience when reconstituting Koāte-DVI."

FDA event • Hemophilia

Assessing a population pharmacokinetic model of a plasma‐derived, von Willebrand factor‐containing FVIII concentrate for Bayesian forecasting in low dose scenarios (EAHAD 2020) - "The Koate-DVI popPK model provides a comparable prediction performance for low and normal Koate-DVI doses. The inclusion of a pre-dose measure leads to an overall greater precision regardless of dose. The Koate-DVI popPK model can be used for Bayesian forecasting on the WAPPS platform in both low dose (10 IU/Kg) and normal dose (50 IU/Kg) scenarios."

Clinical • PK/PD data

NOVEL ADAMTS13 MUTATION IN A PATIENT WITH HEREDITARY TTP TREATED WITH PLASMA-DERIVED FACTOR VIII (ASPHO 2019) - "We present a novel mutation in ADAMTS13 that is likely pathogenic by ACMG guidelines. Our patient demonstrated a response to prophylactic Koate-DVI infusions, which offers several benefits over the administration of FFP."

Clinical