Balugrastim: A long-acting, once-per-cycle, recombinant human albumin-fusion filgrastim.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13551-e13551
Author(s):  
Laurie Pukac ◽  
Steven Barash ◽  
Noa Avisar ◽  
Hermann Allgaier ◽  
Jason Bock ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Half Life ◽  
Human Albumin ◽  
Biologically Active ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Terminal Half Life ◽  
Long Acting ◽  
Dose Dependent

e13551 Background: Balugrastim is a once-per-cycle fixed-dose genetic fusion protein composed of human serum albumin (HSA) and granulocyte colony-stimulating factor (G-CSF) in development for prevention of severe neutropenia in cancer patients receiving chemotherapy. Albumin fusion is a clinically validated technology that extends product half-life, allowing for infrequent dosing, better tolerability, lower cost, and improves drug design, potentially lowering immunogenicity risk. Here, we describe the technology used to produce balugrastim and summarize preclinical findings compared with pegfilgrastim (Neulasta). Methods: Design and production of balugrastim was described previously (Halpern et al. Pharmaceut Res 2002;19:1720−1729). Biologic activity of balugrastim was assessed in an NFS-60 cell line proliferation assay vs filgrastim and pegfilgrastim. PK and PD properties were studied in healthy and neutropenic animal models. Results: Albumin fusion produces a long-acting G-CSF with comparable pharmacologic properties to pegfilgrastim. In vitro, balugrastim had binding affinity and cell proliferation activity comparable to pegfilgrastim, and both were lower than non-PEGylated filgrastim on a molar basis. Overall increases in leukocytes, neutrophilic granulocytes, and monocytes were dose dependent and consistent with the effects expected for a long-acting G-CSF with some variation based on the specific animal model used. A single balugrastim dose in BDF1 mice elicited a dose-dependent increase in peripheral granulocytes and mobilized hematopoietic progenitor cells. In cynomolgus monkeys, balugrastim caused an increase in peripheral neutrophils similar to pegfilgrastim, with higher responses after 2nd, 3rd, and 4th doses. In mice, balugrastim had shorter terminal half-life and mean residence time, and faster clearance than pegfilgrastim. In monkeys, terminal half-life of balugrastim was slightly longer than pegfilgrastim. Conclusions: An albumin fusion technology platform was used to produce balugrastim – a novel, biologically active albumin G-CSF fusion protein with greater structural homogeneity and comparable pharmacologic properties to conventionally PEGylated G-CSFs.

Lipegfilgrastim: A long-acting, once-per-cycle, glycopegylated recombinant human filgrastim.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13548-e13548 ◽  
Author(s):  
Christian Scheckermann ◽  
Karsten Schmidt ◽  
Afsaneh Abdolzade-Bavil ◽  
Hermann Allgaier ◽  
Udo W. Mueller ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Specific Activity ◽  
The Body ◽  
Biologically Active ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Protein Activity ◽  
Reactive Groups ◽  
Long Acting

e13548 Background: Lipegfilgrastim is a once-per-cycle fixed-dose glycoPEGylated granulocyte-colony stimulating factor (G-CSF) under development for the prevention of severe neutropenia in cancer patients receiving chemotherapy (CTx). PEGylation of a molecule extends its half-life in the body, requiring less frequent dosing and allowing for administration of G-CSF once per CTx cycle, making treatment potentially less expensive and enhancing patient compliance and safety. Briefly, traditional PEGylation methods use chemical conjugation through reactive groups on amino acids, which may reduce protein activity and result in non-uniform chemical and pharmaceutical properties. Here, we describe a highly site-specific GlycoPEGylation technology for site-directed PEGylation and summarize preclinical findings compared with pegfilgrastim (Neulasta). Methods: Glycosylation sequon scanning was used to identify the glycoPEGylation site with least impact on protein activity. E. coli-expressed G-CSF was selectively glycosylated at natural O-glycosylation sites and a polyethylene glycol (PEG) sialic acid derivative attached using a sialyltransferase (glycoPEGylation technology). Ligand binding affinity was assessed using the BIACORE 3000 system. Biologic activity of lipegfilgrastim was assessed in an NFS-60 cell line proliferation assay vs filgrastim and pegfilgrastim. PK and PD properties were studied in healthy and neutropenic animal models. Results: GlycoPEGylation produces long-acting G-CSF with improved PK profiles. In vitro, lipegfilgrastim had binding affinity and specific activity comparable to pegfilgrastim, and both were lower than non-PEGylated filgrastim. Comparable increases in leukocytes, neutrophilic granulocytes, and monocytes were seen with lipegfilgrastim and pegfilgrastim in rats and monkeys and were consistent with the effects expected for a long-lasting G-CSF. Conclusions: GlycoPEGylation technology platform is used to produce lipegfilgrastim – a novel, biologically active G-CSF with greater structural homogeneity and comparable pharmacologic properties to conventionally PEGylated G-CSFs.

Prolonged in-vivo half-life of factor VIIa by fusion to albumin

2008 ◽  
Vol 99 (04) ◽  
pp. 659-667 ◽  
Author(s):  
Thomas Weimer ◽  
Wilfried Wormsbächer ◽  
Ulrich Kronthaler ◽  
Wiegand Lang ◽  
Uwe Liebing ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Half Life ◽  
Mammalian Cells ◽  
Factor Viia ◽  
Therapeutic Option ◽  
Human Albumin ◽  
Pharmacokinetic Studies ◽  
Wild Type

SummaryFor the treatment of haemophilia patients with inhibitors, recombinant factor VIIa (rFVIIa) is available as a therapeutic option to control bleeding episodes with a good balance of safety and efficacy. However, the short in-vivo half-life of approximately 2.5 hours makes multiple injections necessary, which is inconvenient for both physicians and patients. Here we describe the generation of a recombinant FVIIa molecule with an extended half-life based on genetic fusion to human albumin. The recombinant FVII albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity close to that of wild type FVIIa. Pharmacokinetic studies in rats demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was extended six- to sevenfold compared with wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and was found to be comparable to a commercially available rFVIIa (NovoSeven®). The results of this study demonstrate that it is feasible to develop a half-life extended FVIIa molecule with haemostatic properties very similar to the wild-type factor.

scholarly journals The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis

2018 ◽  
Vol 19 (9) ◽  
pp. 2683 ◽  
Author(s):  
Ruijing Huang ◽  
Jian Li ◽  
Yibo Wang ◽  
Lihua Zhang ◽  
Xiaohui Ma ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fusion Protein ◽  
Protective Effect ◽  
Half Life ◽  
Integrin Αvβ3 ◽  
Current Treatment ◽  
Pharmacokinetic Studies ◽  
Long Acting

Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVβ3 and α5β1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the inflammatory response. However, due to its short half-life, the anti-RA activity was achieved by frequent administration. To extend the half-life of HM-3, we designed a fusion protein with name HM-3-Fc, by combination of modified Fc segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic lymphocytes and reduced the release of TNF-α from macrophages. The pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg groups, or once in 7 days in the 25 mg/kg group showed a better protective effect within two weeks than the positive control adalimumab and HM-3 group. Preliminary pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM-3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated that an Fc fusion can effectively increase the half-life of HM-3 and make it possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a long-acting active molecule for RA treatment.

Prolonged In-Vivo Half-Life of FVIIa by Fusion to Albumin.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3142-3142 ◽  
Author(s):  
Stefan Schulte ◽  
Thomas Weimer ◽  
Wilfried Wormsbaecher ◽  
Ulrich Kronthaler ◽  
Albrecht Groener ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Half Life ◽  
Mammalian Cells ◽  
Factor Viia ◽  
Therapeutic Option ◽  
Human Albumin ◽  
Pharmacokinetic Studies ◽  
Wild Type

Abstract For the treatment of hemophilia patients with inhibitors, recombinant Factor VIIa (rFVIIa) is available as a therapeutic option to control bleeding episodes with a good balance of safety and efficacy. The short in-vivo half-life of approximately 2.5 h requires multiple injections, which is inconvenient for treaters and patients. Here we describe the generation of a half-life extended recombinant FVIIa molecule based on genetic fusion of FVIIa to human albumin. In this fusion protein the design of the linker sequence is important to optimize the effect of the albumin moiety on FVII activity. The recombinant FVII-albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity comparable to wild type rFVIIa. Pharmacokinetic studies in rats and rabbits demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was 6 to 9 fold extended compared to wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and found comparable to commercially available rFVIIa (NovoSeven®). The results of this study demonstrate that it is feasible to improve the attributes of a rVIIa molecule by extending its half life, while retaining a molecule with very similar hemostatic properties to the wild type factor.

scholarly journals Mechanisms underlying the antifibrotic properties of noninhibitory PAI-1 (PAI-1R) in experimental nephritis

2009 ◽  
Vol 297 (4) ◽  
pp. F1045-F1054 ◽  
Author(s):  
Yufeng Huang ◽  
Wayne A. Border ◽  
Daniel A. Lawrence ◽  
Nancy A. Noble
Keyword(s):  
Half Life ◽  
Stable Form ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Therapeutic Action ◽  
Protease Inhibition ◽  
Ecm Degradation ◽  
Dose Dependent ◽  
Pai 1

Administration of a mutant, noninhibitory PAI-1 (PAI-1R), reduces disease in experimental glomerulonephritis. Here we investigated the importance of vitronectin (Vn) binding, PAI-1 stability and protease binding in this therapeutic effect using a panel of PAI-1 mutants differing in half-life, protease binding, and Vn binding. PAI-1R binds Vn normally but does not inhibit proteases. PAI-1AK has a complete defect in Vn binding but retains full inhibitory activity, with a short half-life similar to wild-type (wt)-PAI-1. Mutant 14-lb is identical to wt-PAI-1 but with a longer half-life. PAI-1K has defective Vn binding, inhibits proteases normally, and has a long half-life. In vitro wt-PAI-1 dramatically inhibited degradation of mesangial cell ECM while the AK mutant had much less effect. Mutants 14-1b and PAI-1K, like wt-PAI-1, inhibited matrix degradation but PAI-1R failed to reverse this inhibition although PAI-1R reversed the wt-PAI-1-induced inhibition of ECM degradation in a plasmin-, time-, and dose-dependent manner. Thus the ability of PAI-1 to inhibit ECM degradation is dependent both on its antiproteinase activity and on maintaining an active conformation achieved either by Vn binding or mutation to a stable form. Administration of these PAI-1 mutants to nephritic rats confirmed the in vitro data; only PAI-1R showed therapeutic effects. PAI-1K did not bind to nephritic kidney, indicating that Vn binding is essential to the therapeutic action of PAI-1R. The ability of PAI-1R to remain bound to Vn even in a high-protease environment is very likely the key to its therapeutic efficacy. Furthermore, because both PAI-1R and 14-1b bound to the nephritic kidney in the same pattern and differ only in their ability to bind proteases, lack of protease inhibition is also keyed to PAI-1R's therapeutic action.

Pharmacokinetics, Pharmacodynamics and Tolerability of a Potent, Non-peptidic, GP IIb/IIIa Receptor Antagonist following Multiple Oral Administrations of a Prodrug Form

1998 ◽  
Vol 79 (01) ◽  
pp. 169-176 ◽  
Author(s):  
Nishit Modi ◽  
Sherron Bullens ◽  
Cheryl Pater ◽  
Michael Lipari ◽  
Kirk Robarge ◽  
...  
Keyword(s):  
Half Life ◽  
Rhesus Monkeys ◽  
Ex Vivo ◽  
Active Form ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
A Value ◽  
Terminal Half Life ◽  
The Right

SummaryRo 44-3888 is a potent and selective antagonist of GP IIb/IIIa. Following IV administration to rhesus monkeys, the (mean ± SD.) clear ance, volume of distribution and terminal half-life of Ro 44-3888 were 4.4 ± 1.8 ml/min/kg, 0.8 ± 0.4 l/kg and 2.5 ± 0.8 h respectively. Oral administration of Ro 48-3657 (1 mg/kg), a doubly protected prodrug form, produced peak concentrations of Ro 44-3888 (152 ± 51 ng/ml), 4.2 ± 2.2 h after dosing. Terminal half-life and estimated bioavailabil ity were 5.1 ± 1.6 h and 33 ± 6% respectively. No effect on blood pressure, heart rate or platelet counts were seen. Adenosine diphosohate (ADP) induced platelet aggregation (PA) and cutaneous bleeding times (CBT) were determined prior to and after the last of 8 daily oral administrations of Ro 48-3657 (0.25 or 0.5 mg/kg) to eight rhesus monkeys. Peak and trough plasma concentrations were proportional to dose and steady state was achieved after the second administration. Inhibition of PA and prolongation of CBT were concentration dependent. The ex vivo IC50 (82 nM) for ADP-mediated PA correlated with a value (58 nM) determined in vitro. The CBT response curve was displaced to the right of the PA curve. CBT was prolonged to ≥25 min when levels of Ro 44-3888 exceeded 190 nM and PA was >90% inhibited. Therefore, in rhesus monkeys, Ro 48-3657 is reproducibly absorbed and converted to its active form, is well tolerated, and has a concentration-dependent effect on PA and CBT. These properties make Ro 48-3657 an attractive candidate for evaluation in patients at high risk for arterial thrombosis.

Recombinant Albumin-Partnering Technology: Development Of Balugrastim, a Novel Long-Acting Granulocyte Colony-Stimulating Factor

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4854-4854 ◽  
Author(s):  
Noa Avisar ◽  
Laurie Pukac ◽  
Liat Adar ◽  
Steve Barash ◽  
Shane Clark ◽  
...  
Keyword(s):  
Half Life ◽  
Rational Design ◽  
Severe Neutropenia ◽  
Carrier Protein ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Myelosuppressive Chemotherapy ◽  
Patients With Cancer ◽  
Long Acting ◽  
Stimulating Factor

Abstract Introduction Various strategies have been used to extend the half-life of therapeutic proteins, including genetic fusion with carrier proteins. One such carrier protein is human serum albumin (HSA), a benign protein with minimal intrinsic biologic activity that is naturally present in the circulation at a high concentration. It has a long half-life (≈19 days in humans) and is highly soluble. Recombinant HSA produced from yeast retains the beneficial stabilizing properties of HSA while minimizing the potential disadvantages of a serum-derived product. Balugrastim, a novel, long-acting recombinant protein composed of HSA and human granulocyte colony-stimulating factor (G-CSF), was developed for once-per-cycle subcutaneous (SC) administration to provide a novel option for the prevention of severe neutropenia in patients with cancer receiving myelosuppressive chemotherapy. The rational design of balugrastim, differences in its protein chemistry compared with pegfilgrastim, and the clinical and practical implications are presented here. Methods During the design phase of balugrastim, HSA was deemed an ideal candidate as a carrier protein because of its wide distribution in the body, long half-life, and low potential for affecting biological activity of G-CSF. A highly engineered proprietary yeast strain was chosen to achieve high levels of expression and quality. Balugrastim is manufactured using recombinant DNA technology in the yeast Saccharomyces cerevisiae in contrast to pegfilgrastim, which is a PEGylated form of a G-CSF expressed in the bacterium Escherichia coli and then modified by chemical conjugation to polyethylene glycol. Balugrastim was purified using a combination of ion exchange and affinity and chromatography techniques. For clinical testing, sensitive immunogenicity and serum concentration assays were developed for the product. Results The manufacturing process produces balugrastim, a 759-amino-acid monomeric protein with a molecular mass of ≈85 kDa. It is a single continuous polypeptide chain in which residues 1–585 correspond to HSA and residues 586–759 correspond to the amino acid sequence of human G-CSF, connected via a peptide bond. The purified protein is >95% pure as determined by N-terminal sequencing. The result is a highly homogeneous product. The manufacturing process is straightforward, requiring no reformulations, additional chemical modifications, or secondary manufacturing, and is a scalable, modular production system. Balugrastim has a pharmacodynamic profile comparable to that of pegfilgrastim. In a clinical trial comparing balugrastim with pegfilgrastim in patients with breast cancer, the half-life of balugrastim 40 mg SC administered once per cycle was 37.7 hours, maximum plasma concentration was 875 ng/mL, and mean area under the concentration–time curve over 144 hours was 60321 h•ng/mL, providing sustained activity in the therapeutic window and stable blood levels (Pukac, MASCC/ISOO, 2012). Corresponding values for pegfilgrastim 6 mg SC were 47.1 hours, 164 ng/mL, and 11554 h•ng/mL, respectively. In this study, and in a randomized phase III trial in patients with breast cancer, balugrastim was noninferior to pegfilgrastim, with a safety profile similar to that of pegfilgrastim and low incidence of immunogenicity (Gladkov, ASCO, 2011). Conclusions Albumin partnering is an established technology used to generate innovative, half-life extended products. This technology formed the basis for the rational design for balugrastim, a novel once-per-cycle G-CSF for the prevention of severe neutropenia in patients with cancer receiving myelosuppressive chemotherapy. The technology provides balugrastim with several advantages, including a consistent, high-quality product with low immunogenic potential and an extended half-life that permits once-per-chemotherapy cycle administration. The low viscosity of balugrastim permits small needle size (29 gauge). Balugrastim, developed as an alternative to pegfilgrastim, has been shown to be noninferior to pegfilgrastim in clinical trials. Disclosures: Avisar: Teva Pharmaceuticals, Inc: Employment. Pukac:Teva Pharmaceuticals, Inc: Employment. Adar:Teva Pharmaceuticals, Inc: Employment. Barash:Teva Pharmaceuticals, Inc: Employment. Clark:Teva Pharmaceuticals, Inc: Employment. Liu:Teva Pharmaceuticals, Inc: Employment. Bock:Teva Pharmaceuticals, Inc: Employment. Shen:Teva Pharmaceuticals, Inc: Employment.

Eflapegrastim, a novel and potent long-acting GCSF for reducing chemotherapy-induced neutropenia: Integrated results from two phase III trials in breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 539-539
Author(s):  
Lee S. Schwartzberg ◽  
Gajanan Bhat ◽  
Jayaram S. Bharadwaj ◽  
Osama Hlalah ◽  
Alvaro Restrepo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Early Stage ◽  
Absolute Risk ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Long Acting

539 Background: Eflapegrastim (E) is a novel long-acting GCSF comprised of recombinant human GCSF covalently linked to human IgG4 Fc fragment via a PEG linker (MW, 72 kDa). E showed increased potency vs pegfilgrastim (P) in preclinical and Phase I and II trials. Two identically designed Phase III pivotal trials (NCT02643420, NCT02953340) were conducted globally with a fixed dose of 13.2 mg E containing 3.6 mg GCSF to evaluate E vs P (6 mg) in pts receiving chemotherapy for early-stage breast cancer. Methods: Each open-label trial randomized pts 1:1 to a single subcutaneous dose of E 13.2 mg/0.6 mL or P 6 mg/0.6 mL on Day 2 of each of four 21-day cycles following Day 1 adj/neoadj docetaxel 75 mg/m2 + cyclophosphamide 600mg/m2 (TC). The primary endpoint was to demonstrate E non-inferiority (NI) to P as measured by mean duration of severe neutropenia (DSN) in Cycle 1. Results: A total 643 intent-to-treat pts (314 E/329 P) with median age 60 yrs (24–88) were enrolled. Cycle 1 mean (SD) DSN was 0.24 (0.581) vs 0.36 (0.789) days for E and P, confirming NI (p < .0001) and suggesting statistical superiority (p < .029). DSN NI was also shown across cycles 2–4. Among subgroups, including elderly (≥65 yrs) and overweight ( > 75kg) pts, DSN was reduced for E vs P. In Cycle 1, E showed an absolute risk reduction for severe neutropenia of 6.5% vs P (27.1% relative risk reduction, p < .043). Neutropenic complications (hospitalization and/or anti-infective use) were 2.9% and 4.0% for E and P (p = ns). Incidence of FN was low for both E and P, 1.6% vs 1.8% in Cycle 1 and 3.2% vs 3.0% overall. ANC profiles showed sustained increased levels for E vs P in the recovery phase across all cycles. Safety profiles were similar for E and P, including primarily for expected hematologic AEs and for bone pain and other musculoskeletal pain. Conclusions: These integrated pivotal trial results confirm a similar safety profile and non-inferiority in reducing neutropenic risk for E at a lower GCSF dose vs P. The data also suggests the potential for increased potency of E to deliver improved clinical benefit, a possibility that warrants further clinical trials. Clinical trial information: NCT02643420, NCT02953340.

scholarly journals Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

Blood ◽  
2012 ◽  
Vol 120 (12) ◽  
pp. 2405-2411 ◽  
Author(s):  
Elena Santagostino ◽  
Claude Negrier ◽  
Robert Klamroth ◽  
Andreas Tiede ◽  
Ingrid Pabinger-Fasching ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Half Life ◽  
Coagulation Factor ◽  
Human Albumin ◽  
Factor Ix ◽  
Recombinant Fusion Protein ◽  
Hemophilia B ◽  
Coagulation Factor Ix ◽  
Human Dose ◽  
Previously Treated

Abstract A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatment-related adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440.

scholarly journals In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

2020 ◽  
Author(s):  
Bo Liang ◽  
Xudong Yuan ◽  
Gang Wei ◽  
Wei Wang ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Povidone Iodine ◽  
Early Stage ◽  
Etiologic Agent ◽  
Dependent Manner ◽  
Forming Technology ◽  
Long Acting ◽  
Dose Dependent

AbstractTo curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

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