Obizur (susoctocog alfa) / Takeda, Ipsen - LARVOL DELTA

TAK-672-4002: A Study of OBIZUR in Adults With Acquired Hemophilia A (AHA) in South Korea (clinicaltrials.gov) - P=N/A | N=9 | Not yet recruiting | Sponsor: Takeda | Initiation date: Sep 2024 ➔ Dec 2024

Trial initiation date • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Genetic Foundations of Nellore Traits: A Gene Prioritization and Functional Analyses of Genome-Wide Association Study Results. (PubMed, Genes (Basel)) - "The prioritized candidate genes were GFRA4, RFWD3, SERTAD2, KIZ, REM2, and ANKRD34B for reproduction; RFWD3, TMEM120A, MIEF2, FOXRED2, DUSP29, CARHSP1, OBI1, JOSD1, NOP58, and LOXL1-AS1 for the carcass; ANKRD34B and JOSD1 for growth traits; and no genes were prioritized for morphological traits. The functional analysis pinpointed the following genes: KIZ (plays a crucial role in spindle organization, which is essential in forming a robust mitotic centrosome), DUSP29 (involved in muscle cell differentiation), and JOSD1 (involved in protein deubiquitination, thereby improving growth). The enrichment of the functional candidate genes identified in this study highlights that these genes play an important role in the expression of reproduction, carcass, and growth traits in Nellore cattle."

Journal • Targeted Protein Degradation • NOP58 • RFWD3

Cross-reacting antiporcine factor VIII inhibitors in patients with acquired hemophilia A. (PubMed, Res Pract Thromb Haemost) - "•Recombinant porcine factor VIII (rpFVIII) is a hemostatic treatment for bleeding in acquired hemophilia A.•The efficacy of rpFVIII can be negatively affected by cross-reacting anti-human FVIII antibodies.•In this cohort, 52% of patients with acquired hemophilia A had baseline cross-reacting antibodies.•Cross-reacting antibodies were associated with decreased FVIII activity levels post-rpFVIII infusion."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Acquired haemophilia: Update in 2024 (PubMed, Rev Med Interne) - "Eradication of inhibitor should be established as soon as the diagnosis is confirmed with steroid alone often associated with cytotoxic agents or rituximab, depending on FVIII activity and inhibitor titer. The purpose of this review is to summarize the epidemiology, etiopathogenesis, diagnosis, treatment of AHA and discuss current recommendations."

Journal • Review • Hematological Disorders • Hemophilia • Immunology • Oncology • Rare Diseases

Real-world use of recombinant porcine sequence factor VIII in the treatment of acquired hemophilia A: EU PASS. (PubMed, Ther Adv Hematol) - P=N/A, P2/3 | "Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is indicated for the treatment of bleeding events (BEs) in adults with acquired hemophilia A (AHA)...Results from this real-world study support the use of rpFVIII for AHA, aligning with findings from the clinical trial of rpFVIII (NCT01178294) in the treatment of BEs in adults with AHA. EUPAS16055; NCT03199794."

Journal • Preclinical • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Hemophilia • Immunology • Rare Diseases

Efficacy and safety of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A. (PubMed, Int J Hematol) - P2/3 | "This phase II/III open-label study evaluated the safety and efficacy of recombinant porcine factor VIII (rpFVIII, susoctocog alfa) in adults with AHA and severe bleeding episodes in Japan (NCT04580407)...This study supports the use of rpFVIII as a novel therapy in the clinical management of patients with AHA in Japan. rpFVIII was approved for treating bleeding episodes in adults with AHA in Japan in 2024."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases

A Study of OBIZUR in Adults With Acquired Hemophilia A (AHA) in South Korea (clinicaltrials.gov) - P=N/A | N=9 | Not yet recruiting | Sponsor: Takeda

New trial • Hematological Disorders • Hemophilia • Rare Diseases

A Survey of Susoctocog Alfa (Genetical Recombination) in Participants With Acquired Haemophilia A (clinicaltrials.gov) - P=N/A | N=25 | Recruiting | Sponsor: Takeda

New trial • Hematological Disorders • Hemophilia • Rare Diseases

Identification of FVIII inhibitors by anti-FVIII ELISA assay and Bethesda assays in tandem to identify anti-Factor VIII inhibitors (ISTH 2024) - "Bovine-based reagents are used to assess for inhibitors in the presence of emicizumab. Porcine-based Bethesda assay measures FVIII inhibition with porcine FVIII therapy (e.g. obizur)... 218 anti-FVIII results were reviewed. 91% of patients showed correlation between ELISA and Bethesda assays whereas 9% did not. 5/218 (2%) patients had positive Nijmegen Bethesda with negative ELISA."

Hematological Disorders • Hemophilia • Rare Diseases

Evaluation of Factor VIII Population Pharmacokinetics and Exposure-Response to Support Dosing of Recombinant Porcine Factor VIII in Patients with Acquired Hemophilia A (ISTH 2024) - P=N/A, P2, P2/3 | "Background: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is indicated for the treatment of bleeding episodes (BEs) in acquired hemophilia A (AHA)... A 2-compartment model with linear elimination and baseline (endogenous) levels of FVIII described FVIII PK. A typical adult patient (70 kg, 65 years, with positive hFVIII and negative pFVIII inhibitors at baseline) had 10.5 dL/h FVIII clearance, 72.8 dL volume of distribution (Vc), and 6.7 h elimination half-life. Patients with bleeding and positive baseline pFVIII inhibitors (n=13) had 10-fold and 2-fold higher median FVIII clearance and Vc, respectively, than those with negative baseline pFVIII inhibitors (n=19; Table 2); patients positive for baseline hFVIII inhibitors had 3.5-fold and 2-fold higher median FVIII clearance and Vc, respectively, than those negative for baseline hFVIII inhibitors (Table 2)."

PK/PD data • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

BLEEDING DUET: A CASE OF SIMULTANEOUS ACQUIRED FACTOR VIII DEFICIENCY AND ACQUIRED VON WILLEBRAND SYNDROME (THSNA 2024) - "The patient was started on immunosuppression with oral prednisone, IV cyclophosphamide and IVIG. She also received factor VIII replacement, Obizur... To the authors knowledge, this is the first documented instance of two acquired bleeding disorders that occurred simultaneously in a single individual. Here we present the diagnostic steps taken to identify and then prove the presence of two distinct acquired autoimmune mediated bleeding entities and documented positive longitudinal response to immunosuppression."

Clinical • Cardiovascular • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hemophilia • Immunology • Multiple Myeloma • Oncology • Pain • Rheumatology • Solid Tumor • Targeted Protein Degradation

Measurement of recombinant porcine factor VIII in patients with congenital haemophilia A and inhibitors in the presence of emicizumab. (PubMed, Haemophilia) - "This study indicates that rpFVIII can be measured in the presence of emicizumab with a bCSA. A calibration curve for the measurement of rpFVIII with bCSA should be established."

Journal • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study. (PubMed, Haemophilia) - P3 | "Good haemostasis was achieved with rpFVIII during the immediate perioperative period. The study was terminated early because the study sponsor and health authorities determined that the risk of anamnestic reactions outweighs the benefits in this study population."

Journal • P3 data • Preclinical • Surgery • Hematological Disorders • Hemophilia • Rare Diseases

Diagnosis and laboratory monitoring of hemophilia A. (PubMed, Hematology Am Soc Hematol Educ Program) - "A Bethesda or modified Bethesda assay should be performed to quantify any inhibitor, and if susoctocog alfa (rpFVIII) is available, then an assay for cross-reacting antibodies should also be performed. Measurement of rpFVIII requires a 1-stage clotting assay, and measurement of patient FVIII while on emicizumab requires a chromogenic assay that does not contain human FX. Close communication is required between the treating clinicians and the laboratory to ensure that the correct tests are performed while patients are receiving treatments."

Journal • Hematological Disorders • Hemophilia • Immunology • Inflammatory Arthritis • Rare Diseases

Agreement between one stage and chromogenic assays in samples from patients receiving recombinant porcine FVIII (Obizur, Susoctocog-alfa). (PubMed, Int J Lab Hematol) - "The relationship between OSA and CSA was not consistent between method or patient. Previously there has been reports of underestimation by CSA in in vitro spiked samples. Investigation into concentration of phospholipids in the APTT reagents may explain some of these variations."

Journal • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

Real-world safety and effectiveness of recombinant porcine sequence factor VIII in acquired haemophilia A: A non-interventional, post-authorization safety study. (PubMed, Haemophilia) - P=N/A | "In this real-world study of rpFVIII for AHA, no new safety signals were identified compared with previous clinical trial findings. Eighty percent of bleeds resolved with rpFVIII treatment."

Journal • Preclinical • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Hemophilia • Rare Diseases

OBINUTUZUMAB INDUCTION AND MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINAEMIA (EHA 2023) - P2 | "Background: Chemoimmunotherapy based on rituximab remains the cornerstone of treating symptomatic patients with Waldenström macroglobulinaemia...Aims: The OBI-1 study (EUDRACT, 2016-005053-20) evaluated the efficacy and safety of obinutuzumab induction and maintenance in patients with relapsed or refractory Waldenström macroglobulinaemia... Our findings suggest that obinutuzumab induction and maintenance may have significant clinical activity in relapsed and refractory Waldenström macroglobulinaemia. Investigated chemotherapy-free induction and maintenance offered prolonged survival with an acceptable toxicity profile that warrants further investigation of obinutuzumab in Waldenström macroglobulinaemia. Induction, relapsed/refractory, Waldenstrom's macroglobulinemia, Maintenance"

Clinical • IO biomarker • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Thrombocytopenia • Waldenstrom Macroglobulinemia

Recombinant Porcine Factor VIII in Patients with Congenital Hemophilia a with Inhibitors Undergoing Surgery: Phase 3, Multicenter, Single Arm, Open-Label Study (ASH 2021) - P3 | "Background: Recombinant porcine factor VIII (rpFVIII, susoctocog alfa, Obizur ® , Baxalta US Inc., a Takeda company, Lexington, MA, USA) is a recombinant, B-domain–deleted, porcine-sequence FVIII indicated for the treatment of bleeding episodes (BEs) in adults with acquired hemophilia A. Thirty to 40% of patients with congenital hemophilia develop inhibitors to human FVIII (hFVIII)... Six of 7 patients who received the study drug and underwent a surgical procedure achieved hemostasis with rpFVIII during the intraoperative and immediate postoperative period. Most patients developed de novo inhibitors or anamnestic reactions. Thus, good hemostasis can be achieved with rpFVIII within the first days after surgery; other bypassing agents should be used if longer clotting factor correction is required."

P3 data • Preclinical • Hematological Disorders • Hemophilia • Infectious Disease • Osteoarthritis • Rare Diseases

[VIRTUAL] Real-World Safety of Emicizumab: The First Interim Analysis of the European Haemophilia Safety Surveillance (EUHASS) Database (ASH 2020) - "However, early data from the first Phase III trial, HAVEN 1, identified a risk for thrombotic microangiopathy (TMA) or thrombotic events (TEs) when emicizumab was used alongside activated prothrombin complex concentrate (aPCC [FEIBA]; dosed on average a cumulative amount of >100 U/kg/24 hours for ≥24 hours) leading to a warning in the label and ongoing safety monitoring...Concurrent treatments included recombinant activated factor VII (rFVIIa; NovoSeven®; n=23 PwHA), factor VIII, (FVIII products other than Obizur®; n=9 PwHA) and aPCC (n=1 PwHA)...No new or emerging safety signals for emicizumab were identified. However, this analysis was limited by the low number of emicizumab treated PwHA—especially in those without FVIII inhibitors, and relatively short exposure time to emicizumab."

Clinical • Real-World Evidence • Cardiovascular • Hematological Disorders • Hemophilia • Myocardial Infarction • Rare Diseases

REAL-WORLD SAFETY AND EFFECTIVENESS OF RECOMBINANT B-DOMAIN–DELETED PORCINE-SEQUENCE FACTOR VIII FOR ACQUIRED HEMOPHILIA A (EAHAD 2023) - P=N/A, P2/3 | "Introduction: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa, Obizur®, Baxalta US Inc., a Takeda company, Bannockburn, IL, USA) is a replacement therapy indicated for the treatment of bleeding episodes (BEs) in adults with acquired hemophilia A (AHA)... Results from this real-world study support the use of rpFVIII for AHA, aligning with findings from the clinical trial of rpFVIII (NCT01178294) in the treatment of BEs in adults with AHA."

Preclinical • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Hemophilia • Immunology • Rare Diseases

Monitoring of Emicizumab in Acquired Hemophilia A (#227) (GTH 2023) - "Monitoring of emicizumab in AHA can be complicated by concomitant medication with recombinant porcine FVIII (susoctocog alfa, rpFVIII) or recovering FVIII activity in the context of remission. Conclusion Modification of coagulation methods allows monitoring of emicizumab, residual FVIII and inhibitor titer in patients with AHA. The monitoring program established here will be helpful for assessing the use of emicizumab in clinical trials and during real-world use."

Hematological Disorders • Hemophilia • Rare Diseases

Long term observation of therapy and outcome in acquired hemophilia A (#122) (GTH 2023) - "Results To explore the impact of different IST strategies (steroids alone vs. steroids plus cyclophosphamide) on patients' survival, a Kaplan Meier survival analysis was performed...The susoctocog alfa therapy of AHA shows promising results regarding the achievement of a complete remission. However, due to the relatively small sample size, more data needs to be collected. Due to the rarity of AHA and a lack of RCTs, retrospective studies like this make a major contribution to provide more precise prognosis and better aftercare for future patients."

Hematological Disorders • Hemophilia • Immunology • Rare Diseases

Study of TAK-672 in Participants With Acquired Hemophilia A (clinicaltrials.gov) - P2/3 | N=5 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Preclinical • Trial completion • Hematological Disorders • Hemophilia • Rare Diseases

Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder. (PubMed, Front Psychiatry) - "Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD...Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry • LINC00461

Study of TAK-672 in Participants With Acquired Hemophilia A (clinicaltrials.gov) - P2/3 | N=5 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Hemophilia • Rare Diseases