Rixubis (nonacog gamma) / Baxter Healthcare, Takeda - LARVOL DELTA

Dominant negative effects of Gln50Arg mutation in the EGF-1 domain of factor IX causes severe Hemophilia B affecting factor IX replacement therapy (ISTH 2024) - "Plasma was in vitro spiked with Alprolix, Rixubis, Benefix or FEIBA. Hemostatic screening revealed normal platelet aggregation and coagulation factor activities, except for FIX activity levels of 5 IU/dL in both brothers and a FXI activity of 39 IU/dL in one boy. FIX antigen concentrations were in the normal range in both boys and their mother, FIX inhibitor screening was negative (Figure 1). After bolus infusion of Alprolix, FIX activity in vivo recovery was within expected range, but thrombin generation indicated weak response to FIX substitution therapies."

Hematological Disorders • Hemophilia • Rare Diseases • EGF

Evaluation of the Safety, Immunogenicity, and Hemostatic Efficacy of Nonacog Gamma (BAX326) in Previously Treated and Naïve Patients with Severe or Moderately Severe Hemophilia B: A Continuation Study (ASH 2018) - P2/3, P3; "For all BEs, a mean (± SD) number of 1.8 (± 1.65) infusions were required until bleed resolution (Table 1). For on-demand treatment, the median ABR was 16.5 (n=13), whereas for overall prophylaxis the median ABR was 1.3 (n=108) (Table 2)."

Clinical • Biosimilar • Gene Therapies • Hematological Disorders • Hemophilia • Immunology

CLINICAL APPLICATION OF EXTENDED HALF-LIFE PRODUCT ALBUTREPENONACOG ALFA (RIX-FP) IN CHILDREN WITH HAEMOPHILIA B (EAHAD 2023) - "All patients had been previously treated with recombinant FIX concentrates [Benefix (Nonacog alfa, Pfizer) and Rixubis (Nonacog gamma, Baxalta) for more than 50 (patients on demand) or 100 EDs (Exposure Days). This study demonstrates the successful transition of CWH B from SHL to rIX-FP."

Clinical • Hematological Disorders • Hemophilia • Ischemic stroke • Rare Diseases

RETROSPECTIVE STUDY OF THE EFFECTIVENESS AND SAFETY OF THE USE OF RIX-FP IN PATIENTS WITH HAEMOPHILIA B. EXPERIENCE OF FOUR CENTRES IN THE REGION OF CASTILLA Y LEÓN (C&L) (EAHAD 2023) - "In the previous treatment, all on FIX-SHL prophylaxis: 6 BeneFIX®, 1 RIXubis®; and 1 Inmunine®. This study in adult/adolescent and paediatric HB patients appears to show that prophylaxis with rIX-FP achieves a better PK profile than previous treatment, prolonging the administration schedule and with greater convenience and better adherence for the patient. It improves haemostatic effectiveness and controls traumatic bleeding events that occur in routine clinical practice."

Retrospective data • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases • Rheumatology

A Post Marketing Surveillance (PMS) Study of RIXUBIS in India (clinicaltrialsregister.eu) - P4 | N=25 | Sponsor: Baxalta Innovations GmbH

New P4 trial • Hematological Disorders • Hemophilia • Rare Diseases • CD4

RIXUBIS Drug Use-Result Survey (Japan) (clinicaltrials.gov) - P=N/A | N=2 | Completed | Sponsor: Baxalta now part of Shire | Recruiting ➔ Completed | N=30 ➔ 2

Enrollment change • Trial completion • Hematological Disorders • Hemophilia • Rare Diseases

Performance of a Chromogenic Factor IX Activity Assay in the Recovery of Factor IX Replacement Therapies (ISTH 2022) - "Aims: To evaluate the recovered activity of seven FIX replacement products including AlphaNine SD, Alprolix, BeneFIX, Idelvion, Rebinyn, Ixinity and Rixubis by a new chromogenic FIX assay. Using acceptance criteria of 100 ± 25 percent recovery, the Chromogenic Factor IX assay accurately quantified 6/7 products across all levels including AlphaNine, Alprolix, BeneFIX, Rebinyn, Ixinity and Rixubis. The mean FIX recovery was 96, 116, 93, 82, 117 and 102% respectively, relative to the theoretical target across all tested levels. There was an over-recovery of Idelvion (albumin fusion recombinant FIX) with a mean recovery of 153%."

Hematological Disorders • Hemophilia • Rare Diseases

Impact of inhibitors on the procoagulant efficacy of bypass agents or hemostatic factors in combination with emicizumab (ISTH 2022) - " Blood from 21 emicizumab-treated patients, 8 with inhibitor, was collected in CTI.Therapeutic doses of rFVIII (100IU/dl octacog-alfa), BPAs (1µg/ml rFVIIa, 5IU/dl aPCC) or 100IU/dl of plasma-derived FIX (pFIX), two standard-half-life-rFIX (Nonacog-alfa and Nonacog-gamma), and extended-half-life-rFIX (albutrepenonacog-alfa) were tested.Clotting time (CT) was evaluated by Rotational Thromboelastometry (ROTEM) and Thrombin Peak by thrombin generation test (TGT) using low tissue factor concentration. Emizicumab-treated samples showed prolonged CT (Fig-1A) and lower thrombin peak values (Fig-1B) than healthy controls and no significant differences were observed between samples with and without inhibitors.Addition of 100IU/dl of all FIX products normalized the CT values similarly to the same dose of rFVIII. Nonacog-alfa was more efficient producing similar effects than the addition of 1μg/ml rFVIIa. aPCC response was stronger."

Clinical • Combination therapy • Hematological Disorders • Hemophilia • Rare Diseases

IN VITRO ANALYSIS OF THE IMPACT OF INHIBITORS ON THE PROCOAGULANT EFFECTS OF BYPASS AGENTS OR HEMOSTATIC FACTORS IN COMBINATION WITH EMICIZUMAB (EHA 2022) - "Spiking with therapeutic doses of 100 IU/dl octocog-alfa (rFVIII), BPAs [1 µg/ml eptacog alfa activated (rFVIIa); 5 U/dl activated prothrombin complex concentrate (aPCC)] or 100 IU/dl of plasma-derived FIX (pFIX), two standard-half-life (SHL) rFIX (nonacog-alfa and nonacog-gamma), and one extended-half-life (EHL) rFIX (albutrepenonacog-alfa) were tested. Conclusion Procoagulant effect of BPAs with emicizumab was similar with or without inhibitors whereas thrombin generation increment produced by rFIX was enhanced in the presence of inhibitors. These results provide a rationale for investigating the concomitant use of rFIX and emicizumab in PwHA with inhibitor in breakthrough bleeding and surgery."

Combination therapy • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

POTENTIAL USE OF FIX CONCENTRATES TO REGULATE THE PROCOAGULANT EFFECT OF EMICIZUMAB (EAHAD 2022) - "Therapeutic doses of replacement factor (rFVIII, Advate) or BPA (rFVIIa, Novoseven) were used... FIXa was almost undetectable in Rixubis and Idelvion (10 IU) while BeneFIX and pFIX showed similar FIXa activity... Small increment of plasma FIX is enough to increase the procoagulant function of EMI and to achieve an effect similar to the obtained with FVIII or BPAs. Future studies are needed to evaluate in vivo efficacy and safety of this combinatory therapy. Financial support: CSL Behring; ISCIII-FEDER (PI19/00631)"

Hematological Disorders • Hemophilia • Rare Diseases

RIXUBIS PMS India (RIXUBIS PMS) (clinicaltrials.gov) - P4; N=25; Completed; Sponsor: Baxalta now part of Shire; Active, not recruiting ➔ Completed; Trial completion date: Dec 2021 ➔ Aug 2021; Trial primary completion date: Dec 2021 ➔ Aug 2021

Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Rare Diseases • CD4 • PCR

[VIRTUAL] Ex vivo Assessment of the Importance of Activated Factor IX (FIXa) Levels in the Procoagulant Effect of Recombinant FIX Concentrates in Emicizumab-treated Patients (ISTH 2021) - "The effect of rFIX (Nonacog-alfa and Nonacog-gamma), rFVIIa, and aPCC were assessed by rotational thromboelastometry (ROTEM) and thrombin generation test (TGT). After blocking FIXa with EGRck, both EGRck-treated rFIX products showed similar procoagulant profiles and lower effects than the untreated ones, demonstrating FIXa contribution in the procoagulant effects of these concentrates (Fig.2B). Conclusions : Global assays suggest that rFIX concentrates produce an enhanced procoagulant effect of emicizumab opening the idea of its usage as alternative treatment for bleedings in emicizumab-treated patients and prove that FIXa levels of rFIX concentrates have an essential contribution in their procoagulant function.Research funded by FIS_Fondos_FEDER_PI19/00631"

Preclinical • Hematological Disorders • Hemophilia • Rare Diseases

RIXUBIS PMS India (RIXUBIS PMS) (clinicaltrials.gov) - P4; N=25; Active, not recruiting; Sponsor: Baxalta now part of Shire; Trial completion date: Apr 2021 ➔ Dec 2021; Trial primary completion date: Apr 2021 ➔ Dec 2021; Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Disorders • Hemophilia • Rare Diseases • CD4 • PCR

A prospective surveillance study in haemophilia B patients following a population switch to recombinant factor IX (nonacog gamma). (PubMed, Haemophilia) - No abstract available

Clinical • Journal • Hematological Disorders • Hemophilia • Rare Diseases

RIXUBIS Drug Use-Result Survey (Japan) (clinicaltrials.gov) - P=N/A; N=30; Recruiting; Sponsor: Baxalta now part of Shire; Trial completion date: Apr 2021 ➔ May 2022; Trial primary completion date: Apr 2021 ➔ May 2022

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

Safety and effectiveness of Rixubis in patients with hemophilia B: A real-world, prospective, postmarketing surveillance study in South Korea. (PubMed, Blood Res) - P=N/A | "Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea."

Clinical • Journal • P4 data • Real-World Evidence • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

RIXUBIS Drug Use-Result Survey (Japan) (clinicaltrials.gov) - P=N/A; N=30; Recruiting; Sponsor: Baxalta now part of Shire; Active, not recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hemophilia • Rare Diseases

ATHN 2: Factor Switching Study (clinicaltrials.gov) - P=N/A; N=310; Completed; Sponsor: American Thrombosis and Hemostasis Network; Active, not recruiting ➔ Completed

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

Safety, Immunogenicity, and Hemostatic Efficacy of Nonacog Gamma in Patients With Severe or Moderately Severe Hemophilia B: A Continuation Study. (PubMed, Clin Appl Thromb Hemost) - P2/3, P3 | "The annualized bleeding rate was considerably lower during prophylactic treatment (median ABR of 1.3 in 108 patients) than during on-demand treatment (median ABR of 16.5 in 13 patients). These results show that in previously treated patients and nonacog gamma-naïve patients, long-term use of nonacog gamma had acceptable safety and tolerability, and was efficacious as a prophylactic treatment for the management of bleeding episodes.NCT01286779, EudraCT: 2010-022726-33."

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

Phase 3 Clinical Trial: Perioperative Use of Nonacog Gamma, a Recombinant Factor IX, in Previously Treated Patients With Moderate/Severe Hemophilia B. (PubMed, Clin Appl Thromb Hemost) - P3 | "No thrombotic events, severe allergic reactions, or inhibitor formation were observed. Nonacog gamma was well tolerated and effective for intraoperative and postoperative hemostatic management of PTPs with hemophilia B.NCT01507896, EudraCT: 2011-000413-39."

Clinical • Journal • P3 data • Allergy • Hematological Disorders • Hemophilia • Pain • Rare Diseases

Takeda provides updates on its hemophilia studies at WFH 2020, reinforcing its commitment to putting patients first and supporting personalized care for people with bleeding disorders (Businesswire) - "Takeda Pharmaceutical Company Limited...today announced a scientific update from the AHEAD real-world study investigating the long-term outcomes associated with ADVATE [antihemophilic factor (recombinant), rAHF] in patients with hemophilia A, presented as an oral presentation at the World Federation of Hemophilia Virtual Summit 2020 (WFH 2020). The update is one of the three abstracts being presented at WFH 2020...Echoing Takeda’s theme at the virtual summit – 'It’s Personal' – the company also shared data from a physician survey in China, providing insights into optimizing personalized care and hemophilia patient management in centers of excellence (COE)."

Clinical data • Observational data • Hemophilia

RIXUBIS PMS India (RIXUBIS PMS) (clinicaltrials.gov) - P4; N=25; Recruiting; Sponsor: Baxalta now part of Shire; Active, not recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases • PCR

[VIRTUAL] A multi-laboratory validation of the Rossix Chromogenic FIX assay (WFH 2020) - "Samples were prepared from spiking rFIX (Benefix, Rixubis) into congenital FIX deficient plasma (George King Biomedical) to FIX levels of 80, 20, 5 and 1 IU/dL...Peak and trough ex vivo samples containing Benefix or Alprolix were included, as was a normal control plasma (Siemens Control N) and plasma from two healthy volunteers... The Rossix Chromogenic FIX assay showed good agreement between laboratories testing multiple sample types across three analyser types."

Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

CSL Behring to attend and sponsor World Federation of Hemophilia first ever virtual summit (PRNewswire) - "...CSL Behring announced today that the company will both attend and sponsor the World Federation of Hemophilia (WFH) first ever Virtual Summit June 14-19, 2020....At the WFH virtual summit, CSL Behring will participate in the WFH Highlights session, 'Humanitarian Aid Program: Past and Future' on Sunday, June 14 from 11:00 am-12:00 pm EDT and host a symposium titled, 'Hemophilia B: Care Across the Spectrum' on Tuesday, June 16 from 12:40-1:40 pm EDT....CSL Behring will also present two posters..."

Live event • Observational data • Hemophilia

Prophylaxis with a recombinant factor IX (BAX326) in pediatric PTPS with hemophilia B (EAHAD 2014) - Abstract #PO087; P=NA, N=23; "Hemostatic efficacy of BAX326 was excellent or good for >96% of bleeds. Hemostatic efficacy in terms of bleed severity was excellent or good in 100% of minor bleeds, 88.9% of moderate bleeds, and 100% of major bleeds; the majority (88.5%) resolved after 1–2 infusions. Incremental recovery (IR) 30 min after infusion was consistent over time. An age effect was observed, with higher IR in association with increased patient age."

Clinical data • Hemophilia