scholarly journals Long‐term safety and efficacy results from the phase 3b, open‐label, multicentre Continuation study of rurioctocog alfa pegol for prophylaxis in previously treated patients with severe haemophilia A

Haemophilia ◽  
2020 ◽  
Vol 26 (4) ◽  
Author(s):  
Pratima Chowdary ◽  
Eric S. Mullins ◽  
Barbara A. Konkle ◽  
Catherine McGuinn ◽  
Young Shil Park ◽  
...  
Keyword(s):  
Haemophilia A ◽  
Severe Haemophilia ◽  
Open Label ◽  
Safety And Efficacy ◽  
Previously Treated Patients ◽  
Previously Treated

Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A

2017 ◽  
Vol 117 (09) ◽  
pp. 1705-1713 ◽  
Author(s):  
Sandrine Meunier ◽  
Jayanthi Alamelu ◽  
Silke Ehrenforth ◽  
Hideji Hanabusa ◽  
Faraizah Abdul Karim ◽  
...  
Keyword(s):  
Half Life ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Older Children ◽  
Open Label ◽  
Paediatric Patients ◽  
Effective Prophylaxis ◽  
History Of ◽  
Previously Treated Patients ◽  
Previously Treated

SummaryTuroctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0–5 years [younger cohort]; >150 ED for patients aged 6–11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50–75 IU/kg twice weekly; bleeds were treated with 20–75 IU/kg. Half-life was estimated for the patients’ previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients’ previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.Trial registered at www.clinicaltrials.gov (NCT01731600).Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B

2020 ◽  
Vol 120 (05) ◽  
pp. 737-746
Author(s):  
Manuel Carcao ◽  
Susan Kearney ◽  
Meng Yao Lu ◽  
Masashi Taki ◽  
Daniel Rubens ◽  
...  
Keyword(s):  
Factor Ix ◽  
Hemophilia B ◽  
Phase Iii ◽  
Open Label ◽  
Safety And Efficacy ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Inhibitory Antibodies

AbstractLong-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40 IU/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged ≤ 12 years with HB (FIX activity ≤ 2%). Primary endpoint: incidence of anti-FIX inhibitory antibodies (≥ 0.6 Bethesda Units). We present a 5-year analysis (N = 25, including remaining patients with ≥ 5 years' follow-up) and compare with a 1-year analysis (≥ 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years/patient; median total number of N9-GP exposure days: 290.0/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild/moderate in severity; 93.0% were controlled with 1 to 2 N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median/Poisson-estimated mean overall ABR: 0.66/0.99), having decreased from the 1-year analysis (1.00/1.44). Median/Poisson-estimated mean spontaneous ABRs for the 1- and 5-year analyses: 0.00/0.45 and 0.00/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for ≥ 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity ≤ 2%).

Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A

2017 ◽  
Vol 117 (02) ◽  
pp. 252-261 ◽  
Author(s):  
Paul Giangrande ◽  
Tatiana Andreeva ◽  
Pratima Chowdary ◽  
Silke Ehrenforth ◽  
Hideji Hanabusa ◽  
...  
Keyword(s):  
Randomised Trial ◽  
Phase Iii ◽  
Haemophilia A ◽  
Activity Levels ◽  
Severe Haemophilia ◽  
Open Label ◽  
Favourable Safety Profile ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Recombinant Fviii

SummaryTuroctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20–75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00–4.61), the mean ABR was 3.70 (95 % confidence interval 2.94–4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.

Evaluation of pharmacokinetics, efficacy and safety of Immunate�solvent detergent in previously treated patients with severe haemophilia A

Haemophilia ◽  
2007 ◽  
Vol 13 (1) ◽  
pp. 9-11 ◽  
Author(s):  
L. NEMES ◽  
T. LISSITCHKOV ◽  
A. KLUKOWSKA ◽  
G. DOBACZEWSKI ◽  
V. KOMRSKA ◽  
...  
Keyword(s):  
Haemophilia A ◽  
Severe Haemophilia ◽  
Efficacy And Safety ◽  
Previously Treated Patients ◽  
Previously Treated

Human-Cl Rhfviii Effectively and Safely Prevents Bleeding Episodes in Previously Treated Adult Patients with Severe Haemophilia A

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1132-1132
Author(s):  
Sigurd Knaub ◽  
Toshko Lissitchkov ◽  
Kingsley Hampton ◽  
Mario Von Depka ◽  
Savita Rangarajan ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Research Funding ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Open Label ◽  
Bleeding Rate ◽  
Previously Treated

Abstract Abstract 1132 The main purpose of this prospective, multi-center, open-label phase 3 study was to assess the efficacy of prophylactic treatment with Human-cl rhFVIII, the first human cell-line derived recombinant FVIII, in previously treated patients (PTPs) with severe haemophilia A. Patients were to receive 30–40 international units (IU) FVIII of Human-cl rhFVIII per kg every other day for 6 months. Efficacy of preventing and treating bleeds were judged using objective criteria taking the monthly bleeding rate and the number of infusions needed to manage a break-through bleed into account. In-vivo recovery (IVR) was determined at the beginning of the study and after 3 and 6 months. FVIII:C was measured by validated chromogenic (CHR) and one-stage (OS) assays in a central laboratory, which also assigned drug potencies. Inhibitor activity was determined using the Nijmegen modification of the Bethesda assay before the first administration and at defined intervals thereafter. Thirty-two patients between 18 and 75 years of age were enrolled from 11 centres in Europe and treated prophylactically for 6.0±0.9 months (mean ± SD) with a mean prophylactic dose of 32.8 IU/kg. Sixteen patients never bled, 11 patients bled once and 5 more than once. The mean total and spontaneous monthly bleeding rate was 0.188±0.307 and 0.095±0.211, respectively. Efficacy of the prophylactic treatment was “excellent” in all patients for spontaneous BEs and “excellent” or “good” in all patients but one for all types of bleeds. All treatments of bleeds were rated as “excellent” (71.4%) or “good” (28.6%). The IVR at baseline was 2.6±0.5 % per IU/kg for the CHR and 2.2±0.5 % per IU/kg for the OS assay and remained stable during the study. A total of 2921 infusions were given in the study. Human-cl rhFVIII was well tolerated and no patient experienced a related serious adverse event. No FVIII inhibitors were detected. Conclusion: The data indicate that Human-cl rh FVIII is safe and efficacious in preventing and treating bleeds in PTPs with severe haemophlia A. Disclosures: Knaub: Octapharma AG: Employment. Lissitchkov:Octapharma AG: PI Other. Tuddenham:College London: Consultancy, Employment, Gene therapy for hemophilia A, Gene therapy for hemophilia A Patents & Royalties, Research Funding. Collins:Octapharma AG: Consultancy. Oldenburg:d and e: Baxter, Bayer, Biotest, CSL-Behring, Grifols, Inspiration, NovoNordisk, Octapharma, Pfizer e: Biogen IDec, Swedish Orphan Biovitrum: Honoraria, Research Funding. Bichler:Octapharma AG: Employment.

Efficacy and Safety Results of Prolong-9FP Clinical Program of Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Previously Treated Patients with Hemophilia B

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 548-548 ◽  
Author(s):  
Elena Santagostino ◽  
Christine Voigt ◽  
Denise Wolko ◽  
Grace Cole ◽  
Yanyan Li ◽  
...  
Keyword(s):  
Day Treatment ◽  
Hemophilia B ◽  
Spontaneous Bleeding ◽  
Safety And Efficacy ◽  
On Demand ◽  
Routine Prophylaxis ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes

Abstract A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP) has been developed with an improved PK profile, thus improving hemophilia B treatment by allowing less frequent dosing. Two Phase 3 studies (CSL654-3001 and CSL654-3002) were completed. CSL654-3001 study evaluated safety and efficacy of rIX-FP for prophylaxis treatment (PT) of every 7-, 10- and 14-day and on-demand (ODT) of bleeding episodes in 63 previously treated patients (PTP), 12-61 years of age with hemophilia B (FIX ≤ 2%). Subjects in the on-demand arm received only ODT for 6 months and then switched to every 7-day PT. Subjects in the prophylaxis arm received every 7-day PT, and eligible subjects switched to every 10- or 14-day PT for approximately 12-18 months. Annualized spontaneous bleeding rates (AsBR) were compared between ODT and PT periods (in on-demand arm), and between 7-day PT and 10- or 14-day PT (in prophylaxis arm). CSL654-3002 study evaluated safety and efficacy of rIX-FP for weekly prophylaxis regimen in 27 previously treated patients younger than 12 years with hemophilia B (FIX ≤ 2%) for approximately 12 months. Annualized spontaneous bleeding rates (AsBR) were calculated. The median annualized spontaneous bleeding rate were all 0.00 for all treatment interval (7-day, 10-day or 14-day) and in both studies age groups (1-11 years and 12-65 years) during the two completed phase 3 studies. Seventy-six subjects from both studies continued their prophylaxis regimen in the on-going extension study. In addition, subjects (including children), switched to longer treatment intervals of 10-day, 3 times per month or 14-day or lowered their weekly prophylaxis dose. Nine subjects switched to 21-day treatment interval with 100 IU/kg rIX-FP. As of 28 July 2015, at least 50 subjects (PTP) had achieved 100 EDs without developing an inhibitor to FIX or antibodies to rIX-FP. The long term safety and efficacy of rIX-FP will be presented. This presentation includes the new information regarding the change to longer than 7-day treatment regimens in the extension study, among those subjects (1-61 years of age) that previously participated in the lead in studies. Conclusion: The Prolong - 9FP clinical programdemonstrated the clinical efficacy of rIX-FP for routine prophylaxis every 7-, 10- and 14-day treatment intervals. Routine prophylaxis once every 21 days may be effective in preventing bleeding episodes in a selected patient population. In addition, rIX-FP demonstrated favorable long-term safety and tolerability. Disclosures Santagostino: Novo Nordisk: Speakers Bureau; Bayer: Speakers Bureau; CSL Behring: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Biogen/Sobi: Speakers Bureau; Biotest: Speakers Bureau; Kedrion: Speakers Bureau; Octapharma: Speakers Bureau; Roche: Speakers Bureau. Voigt:CSL Behring: Employment. Wolko:CSL Behring: Employment. Cole:CSL Behring: Employment. Li:CSL Behring: Employment. Jacobs:CSL Behring: Employment.

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