scholarly journals Real-World Effectiveness and Safety of BAY 94-9027 (Damoctocog Alfa Pegol) in Previously Treated Patients with Hemophilia A (HEM-POWR): Online Patient Portal and LIFE-ACTIVE Sub-Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4943-4943
Author(s):  
Johannes Oldenburg ◽  
María Teresa Alvarez Román ◽  
Giancarlo Castaman ◽  
Maissaa Janbain ◽  
Tadashi Matsushita ◽  
...  
Keyword(s):  
Study Design ◽  
Real World ◽  
Research Funding ◽  
Hemophilia A ◽  
Patient Portal ◽  
The Real ◽  
Patient Reported ◽  
Previously Treated Patients ◽  
Previously Treated

Background and Rationale: BAY 94-9027 (damoctocog alfa pegol) is a site-specifically PEGylated B-domain deleted recombinant factor VIII (FVIII) with an extended half-life, approved for prophylaxis or treatment of bleeds in previously treated patients (PTPs) aged ≥12 with hemophilia A. The efficacy and safety of BAY 94-9027 was demonstrated in two phase II/III clinical studies in PTPs with severe hemophilia A, however, real-world data are still being gathered. The aim of the HEM-POWR study is to assess the effectiveness and long-term safety of BAY 94-9027 in the real-world clinical setting. Patients will be introduced to an online patient portal that provides study information as well as access to eDiaries and electronic patient-reported outcomes (ePROs) to patients to facilitate retention over the duration of the study. Patients will also be given the opportunity to participate in LIFE-ACTIVE, a sub-study analyzing the relationship between the patients' regular daily activity and the efficacy parameters collected during HEM-POWR. Here we present the features of the patient portal and describe the LIFE-ACTIVE sub-study design. Study Design and Methods: HEM-POWR (NCT03932201) is a multinational, multicenter, non-interventional, open-label, prospective, phase IV, cohort study. It aims to enroll ≥200 PTPs with hemophilia A receiving BAY 94-9027 (on-demand, prophylaxis, or intermittent prophylaxis [as per local label]). Key exclusion criteria are presence or history of FVIII inhibitor (≥0.6 Bethesda units), diagnosis of any bleeding or coagulation disorder other than hemophilia A, or treatment with immune tolerance induction at enrollment. The primary objective of HEM-POWR is to assess the effectiveness of prophylaxis with BAY 94-9027 in the real-world setting through the collection of total bleeding events and analysis of annualized bleeding rate. Secondary objectives include long-term safety, joint health, location and number of target joints, hemostasis during surgery and PROs. Patient enrollment, adherence and retention can be difficult in observational hemophilia studies. The patient portal for this study aims to overcome these challenges by providing study- and product-related information. It also aims to lessen the burden for patients in the study by providing e-solutions to collect their study data, including the ability to complete the study diary, and PRO measures online. The portal also includes videos explaining the study and study procedures, and is country-customized with links to relevant websites. Patients participating in LIFE-ACTIVE will be asked to wear an ActiGraph CP Insight activity-tracking smart watch continually for four 30-day periods, at their initial visit and then at months 12, 24 and 36. Measurements recorded will include physical activity intensity and duration, general mobility, and sleep quality and duration. All data will be transferred to a secure, cloud-based system and patients will not be aware of the values measured by the device. Participating countries include, but may not be limited to Austria, Belgium/Luxemburg, Canada, Colombia, Finland, Germany, Greece, Italy, Japan, Netherlands, Portugal, Saudi Arabia, Denmark, Norway, Sweden, Slovenia, Spain, Switzerland, Taiwan, and USA. The study will run from 2019 until 2025, with an observation period of ≥60 months. Disclosures Oldenburg: Octapharma: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Takeda (Shire): Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; Swedish Orphan Biovitrum: Consultancy, Speakers Bureau. Alvarez Román:CSL Behring: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Sobi: Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Shire (Takeda): Research Funding, Speakers Bureau. Castaman:Shire: Speakers Bureau; Uniqure Kedrion: Speakers Bureau; Pfizer: Research Funding; CSL Behring: Research Funding, Speakers Bureau; Bayer: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Sobi: Research Funding, Speakers Bureau. Janbain:Shire (Vonvendi): Speakers Bureau; Genentech: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Shire: Consultancy, Honoraria; HTRS-MRA (Bioverativ Sanofi): Research Funding. Matsushita:uniQure: Consultancy, Honoraria; CSL: Consultancy, Honoraria; Bioverative: Research Funding; Pfizer: Consultancy, Honoraria; KM biologists: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria. Meijer:Sanquin: Research Funding; Pfizer, Sanquin, Uniqure: Research Funding; Uniqure, BMS, Aspen, Boehringer Ingelheim, Sanquin, Bayer: Consultancy, Honoraria; Bayer: Research Funding. Sanabria:Bayer: Employment. Reding:Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Biomarin: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.

Immunogenicity of BAX 855 in Previously Treated Patients with Congenital Severe Hemophilia Α

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2594-2594
Author(s):  
Frank Michael Horling ◽  
Peter Allacher ◽  
Herwig Koppensteiner ◽  
Werner Engl ◽  
Fritz Scheiflinger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neutralizing Antibodies ◽  
Research Funding ◽  
Hemophilia A ◽  
De Novo ◽  
Coagulation Factor ◽  
Severe Hemophilia ◽  
Increased Risk ◽  
Previously Treated Patients ◽  
Previously Treated

Abstract Background and objectives BAX 855 (Antihemophilic Factor [Recombinant] pegylated, rurioctocog alfa pegol) is an extended half-life (EHL) recombinant human coagulation factor VIII (rFVIII) modified with polyethylene glycol (PEG) (Turecek et al., 2012). It was recently approved in the US and Japan for on-demand treatment of bleeding events and for prophylactic treatment for patients with congenital severe hemophilia A. The efficacy and safety of BAX 855 were extensively studied during clinical development of this compound (Konkle et al., 2015). The assessment of BAX855 immunogenicity was of particular interest because the development of neutralizing antibodies (FVIII inhibitors) is the most serious complication following replacement therapies with FVIII products. FVIII inhibitors develop in about 20-32% of previously untreated patients (Gouw SC et al., 2013) and with a rate of 1.55- 3.8 per 1000 patients per year in previously treated patients (Kempton CL, 2010) with severe hemophilia A. To fully understand the potential of BAX855 to induce antibody responses, both FVIII inhibitors and total FVIII-binding antibodies were assessed. Furthermore, potential antibody development against PEG-FVIII, PEG and CHO proteins was investigated. Methods The clinical protocols (ClinicalTrials.gov identifier: NCT02585960, NCT02210091, NCT01736475, NCT01913405, NCT01945593, NCT01599819, NCT02615691) and the methods used for antibody analytics (Whelan et al 2013; Lubich et al 2016) were previously described. ELISA technologies were used for the analysis of total binding antibodies, the Nijmegen modification of the Bethesda assay was used for the detection of FVIII inhibitors. Correlation analyses were done to assess any potential correlation between the development of antibodies and potential adverse events. Results None of the 243 subjects (6 PUPs and 237 PTPs) included in the analysis developed FVIII inhibitors (≥ 0.6 BU/mL) A total of 44 subjects tested positive for binding antibodies against FVIII, PEG-FVIII or PEG at single time points. 28 of these 44 subjects showed pre-existing antibodies against FVIII, PEG-FVIII, or PEG prior to first exposure to BAX 855, which disappeared during the study. 13 subjects who tested negative at screening developed transient antibodies against FVIII, PEG-FVIII, or PEG at one or two consecutive study visits after exposure to BAX 855. Antibodies were transient and not detectable at subsequent visits or at completion of the study. Five subjects showed positive results for binding antibodies at study completion or at the time of the data cutoff. No conclusion can be drawn whether these antibodies are of transient or persistent nature. There was no confirmed causal relationship between the appearance of binding antibodies against FVIII, PEG or PEG-FVIII and adverse events, nor was there an impact on hemostatic efficacy in any of the 44subjects. No subject had pre-existing antibodies or developed de novo antibodies to CHO proteins during the study at any time point. Conclusion Our data indicate that BAX855 did not show an increased risk for PTPs to develop FVIII inhibitors. We did not see any FVIII inhibitor development in PUPs, but the small number of overall exposures does not allow general conclusions for PUPs. Importantly, the data suggest that BAX855 did not induce immune responses associated with impaired treatment efficacy or with altered PK parameters. Disclosures Horling: Shire: Employment. Allacher:IMC Krems: Research Funding. Koppensteiner:Shire: Employment. Engl:Shire, formerly Baxalta and Baxter: Employment, Equity Ownership. Scheiflinger:Shire: Employment, Research Funding. Abbuehl:Baxalta (now part of Shire): Employment. Reipert:Shire: Employment.

scholarly journals 99.3% of Inhibitors in Severe Hemophilia a Develop before Exposure Day 75. Time to Change Definition of Previously Treated Patients; Data from 1038 Patients with Severe Hemophilia a of the Pednet Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2472-2472
Author(s):  
Marijke Van den Berg ◽  
Kathelijn Fischer ◽  
Elena Santagostino ◽  
Herve Chambost ◽  
Karin Kurnik ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Advisory Committees ◽  
Inhibitor Development ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Definition Of

Abstract Introduction.In patients with hemophilia treated with factor VIII products, the development of inhibitory antibodies poses the largest safety risk. Especially during the first 50 exposure days (EDs), up to 37% of patients with severe hemophilia A have been reported to develop an inhibitor. To study neo-immunogenicity of products and new treatment strategies, patients have been distinguished into previously untreated (PUPs) and previously treated patients (PTPs); the latter defined as patients treated for more than 150 EDs. The number of 150 EDs was established in the eighties during a time when most patients received on-demand treatment and testing for inhibitors was not frequently performed. More recent studies on inhibitor incidence in PUPs with severe hemophilia A report that 50% of inhibitors develop within 14-15 EDs, however the cut-off number of EDs for a PUP to become a PTP is not well defined. The aim of this study was to define the number of EDs for PUPs to become PTPs based on long-term follow-up of patients with severe hemophilia A Methods.All patients with severe hemophilia A born after January 1, 2000, treated for at least 1 ED and followed prospectively until inhibitor development or the number of EDs at last follow-up, were included. The number of EDs at inhibitor development is the last exposure day before the first positive titer was reported. An inhibitor was defined as positive when at least two positive inhibitor titers were measured. Positivity was defined according to the cut-off level in each individual center's laboratory. Results.Of 1,038 PUPs with severe hemophilia A, 930 (89.6%) were followed until 75 EDs, 429 until 500 EDs and 212 until 1000 EDs. In total, 300 inhibitors developed, of which 298 (99.3%) within the first 75 EDs. Thereafter only two inhibitors developed, both low titer: after 249 and 264 EDs. Conclusion.Almost all inhibitors develop during the first 75 EDs. Patients with severe hemophilia A can be defined as PTP after 75 instead of 150 exposure days. A change of definition of PTP will increase the number of severe hemophilia A patients eligible for new therapies. Disclosures Santagostino: Bioverativ: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees. Male:SOBI: Speakers Bureau; Shire: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Speakers Bureau; Novo Nordisk: Speakers Bureau; Biotest: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Oldenburg:Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Liesner:Baxalta: Consultancy, Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Sobi: Speakers Bureau; Bayer: Consultancy, Research Funding; Roche: Research Funding; Octapharma: Consultancy, Other: Clinical study investigator for NuProtect Study (Octapharma sponsored), Research Funding, Speakers Bureau. Carcao:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL-Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; LFB: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nolan:CSL Behring: Research Funding; Sobi: Research Funding; Bayer: Research Funding. Álvarez-Roman:Shire: Consultancy; NovoNordisk: Consultancy; SOBI: Consultancy. Koenigs:Gilead: Research Funding; CSL Behring: Consultancy, Research Funding; Pfizer: Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Intersero: Research Funding; Bioverativ: Consultancy; Roche/Chugai: Consultancy; EU (IMI, FP7): Research Funding; Sobi: Consultancy, Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding; Novo Nordisk: Consultancy, Speakers Bureau; Biotest: Research Funding, Speakers Bureau; Jansen: Research Funding.

Surgery with Turoctocog Alfa: Efficacy and Safety in Bleeding Prevention During Surgical Procedures - Results From the guardian™ Trials.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2228-2228
Author(s):  
Elena Santagostino ◽  
Steven R. Lentz ◽  
Mudi Misgav ◽  
Brigitte Brand ◽  
Pratima Chowdary ◽  
...  
Keyword(s):  
Research Funding ◽  
Hemophilia A ◽  
Efficacy And Safety ◽  
Advisory Boards ◽  
Surgical Bleeding ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Hemostatic Efficacy ◽  
The Guardian ◽  
Extension Trial

Abstract Abstract 2228 Introduction: Novo Nordisk is developing turoctocog alfa, a human third generation recombinant FVIII for treatment of hemophilia A. During the pivotal trial in adult and adolescent previously treated patients with severe hemophilia A (guardian™1), subjects in need of surgery were able to participate in a subtrial to document efficacy and safety of turoctocog alfa in prevention of surgical bleeding. Pediatric (<12 years of age) previously treated patients in the guardian™3 trial were allowed to undergo minor surgery if needed during the trial. In addition, after completing these initial trials subjects were allowed to continue treatment with turoctocog alfa in the extension trial (guardian™2) which also includes a subtrial to document efficacy and safety of turoctocog alfa in prevention of surgical bleeding. Methods: We here describe surgeries performed within the guardian trials. For the ongoing guardian™2 extension trial, only cases included in the interim analysis (data cut-off 21NOV2011) are included. Results: In all, results from 10 major and 3 minor surgeries are included. Surgery indication was related to hemophilia joint disease in 8/13 cases. The hemostatic efficacy during and after surgery was rated on a 4-point scale (excellent, good, moderate and none) by the Investigator and/or Surgeon. Details and outcome of the individual surgeries performed are presented in Table 1. In addition, there were no safety concerns. Discussion: Prevention of surgical bleeding is an important aspect of hemophilia treatment. In the present 13 surgeries, including all surgeries performed with turoctocog alfa in the phase 3 guardian™ trials, hemostatic efficacy during and after was rated as either excellent or good in each case. The results support that turoctocog alfa has an excellent safety and efficacy profile for use in hemophilia A. Disclosures: Santagostino: Novo Nordisk and Pfizer: Research Funding; Pfizer, Baxter, Bayer, CSL Behring, Kedrion, Grifols and Novo Nordisk: Consultancy; Bayer, Baxter, Pfizer, CSL Behring, Novo Nordisk, Biotest, Kedrion and Grifols: Speakers Bureau. Lentz:Novo Nordisk: Consultancy, Research Funding. Brand:Bayer: Travel support, Travel support Other; Novo Nordisk, Baxter, Pfizer: Advisory Boards, Advisory Boards Other; Novo Nordisk: Honoraria. Chowdary:Novo Nordisk: Consultancy. Savic:Novo Nordisk: Speakers Bureau. Lindblom:Novo Nordisk A/S: Employment.

scholarly journals Effectiveness and Safety Outcomes in Patients with Hemophilia a Receiving Antihemophilic Factor (Recombinant) for at Least 5 Years in a Real-World Setting: 6-Year Interim Analysis of the Ahead International and German Studies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Dimitrios A. Tsakiris ◽  
Johannes Oldenburg ◽  
Robert Klamroth ◽  
Benoît Guillet ◽  
Kate Khair ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Interim Analysis ◽  
Research Funding ◽  
Hemophilia A ◽  
Routine Clinical Practice ◽  
Publicly Traded ◽  
Real World Setting ◽  
Antihemophilic Factor

Introduction: Long-term effectiveness and safety data in patients treated in routine clinical practice settings can be captured from real-world studies. The international (INT) and German (GER) Antihemophilic factor (recombinant; rAHF) Hemophilia A (HA) outcome Database (AHEAD) studies assess long-term effectiveness and safety outcomes in patients with moderate HA (factor VIII level 1-5%) or severe HA (factor VIII &lt;1%) receiving rAHF (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) in routine clinical practice. Methods: These are non-interventional, prospective, long-term, multicenter studies (INT: NCT02078427; GER: DRKS 00000556). Key outcomes include Gilbert scores (primary endpoint; pain scored 0-3; bleeding scored 0-3, and physical exam scored 0-12), annualized bleeding rates (ABRs) by disease severity, and adverse events (AEs). Findings reported here are from the 6-year interim analysis (data cut-off: July 15, 2019), and focus on patients who have received rAHF prophylaxis or on-demand (OD) treatment for ≥5 years in the studies. All data are reported for the safety analysis set (SAS), which comprised patients who passed screening and were assigned to a treatment group or regimen in the INT study, or were enrolled and have received ≥1 dose of rAHF since study enrollment in the GER study. Results: At the time of analysis, the INT study SAS comprised 707 patients, 156 of whom had received ≥5 years of rAHF treatment during the study. The GER study SAS comprised 382 patients, 231 of whom had received ≥5 years of rAHF treatment. Average Gilbert scores (all joints) were consistently low (years 1-6: median 0-1.0; mean 0-1.3) for both children aged 2 to &lt;12 years and adolescents aged 12 to &lt;18 years receiving rAHF prophylaxis within both studies. In the INT study, average Gilbert scores were lower with prophylaxis than with OD therapy in adults (aged ≥18 years) throughout the observation period (years 1-6: median: 0.9-1.4 [n=8-25] vs 1.4-6.3 [n=2-8], respectively; mean: 1.4-2.2 vs 2.1-6.3; respectively); significant differences (P&lt;0.05) between mean values were observed for years 3, 4, and 6. In the GER study, average Gilbert scores were slightly higher with prophylaxis than with OD in adults (years 1-6: median: 0.7-2.2 [n=12-37] vs 0.3-1.4 [n=2-15], respectively; mean: 1.0-2.7 vs 0.5-2.2, respectively; P-values not available). In the INT study, ABRs were consistently lower in patients receiving rAHF prophylaxis than in those receiving rAHF OD, irrespective of disease severity (Table). A similar trend was observed in the GER study in patients with severe HA, whereas ABRs were similar for both treatment regimens in patients with moderate HA. In both studies, greater proportions of patients with moderate or severe HA receiving rAHF prophylaxis had 0 bleeds than those receiving rAHF OD (Table). In the INT study, 842 AEs were reported in 116/156 (74.4%) patients, including 2 treatment-related serious AEs in 2 (1.3%) patients. In the GER study, 1321 AEs were reported in 197/231 (85.3%) patients, including 29 treatment-related serious AEs in 14 (6.1%) patients. Conclusions: These findings in patients receiving rAHF for ≥5 years in a real-world setting corroborate previous data on the long-term efficacy and tolerability of rAHF in patients with moderate or severe HA. rAHF demonstrated effectiveness in maintaining joint health (as measured by Gilbert scores) in adult patients. Table Disclosures Tsakiris: Roche: Research Funding; Shire, a Takeda company: Research Funding; Sobi: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding. Oldenburg:Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Klamroth:Pfizer: Consultancy, Research Funding, Speakers Bureau; Biotest: Speakers Bureau; Grifols: Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Guillet:CSL Behring: Research Funding, Speakers Bureau; Octapharma: Research Funding; Bayer: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Speakers Bureau; Roche-Chugai: Consultancy, Speakers Bureau. Khair:Shire, a Takeda company: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Baxalta/Shire, Takeda companies: Research Funding. Huth-Kühne:Bayer: Consultancy; CSL Behring: Consultancy; Shire, a Takeda company: Consultancy; Sobi: Consultancy. Kurnik:Sobi: Consultancy, Research Funding; Biotest: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau. Regensburger:Takeda Pharma Vertrieb GmbH & Co. KG: Current Employment, Current equity holder in publicly-traded company. Botha:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Fernandez:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Tang:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Ozelo:Pfizer: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Bioverativ/Sanofi: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau.

scholarly journals Bay 81-8973 in the Real World: Clinical Effectiveness and Safety in Patients with Hemophilia Α across the US and Europe

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5044-5044
Author(s):  
Jamie O'Hara ◽  
Ceri Hirst ◽  
Stephan Rauchensteiner ◽  
Tom Burke
Keyword(s):  
Real World ◽  
Hemophilia A ◽  
Severe Disease ◽  
Primary Objective ◽  
Severe Hemophilia ◽  
Cross Sectional ◽  
Psychological Burden ◽  
The Real ◽  
Patient Reported ◽  
The Us

Abstract Background: BAY 81-8973 (Kovaltry®, Bayer) is an unmodified full-length recombinant FVIII launched in 2016 in Europe and the US for the prophylaxis and treatment of bleeds in patients with hemophilia A. BAY 81-8973 has been extensively studied in clinical trials, which have demonstrated consistent efficacy and safety in both children and adults in the LEOPOLD trials, and since launch, 6750 patient-years of experience have been accumulated. Pharmacokinetic analyses have demonstrated an increased half-life for BAY 81-8973 compared with standard factor VIII products (rFVIII-FS and rFVIII [rAHF-PFM]). Real world evidence demonstrating the effectiveness and safety of BAY 81-8973 across age groups is being collected, though aggregated international data have yet to be published. The primary objective of this analysis was to describe the effectiveness of BAY 81-8973 in the real world setting in children and adults from Europe and the US, as captured in the Cost of Haemophilia: a Socioeconomic Survey (CHESS) study. Methods: The CHESS 2018 program investigated the economic and psychological burden of moderate and severe hemophilia (FVIII < 5%) in Europe and the USA. The pediatric cohort (CHESS Pediatric) included 1050 males aged 1-17 years, with moderate or severe hemophilia, while CHESS US included 568 adults with severe hemophilia aged > 18 years. Clinical and patient reported data were obtained via medical chart abstraction and cross-sectional surveys sent to both physicians and patients. Data were collected between December 2017 and April 2018, and captured 12 months of clinical retrospective data. The current study is a descriptive analysis of patients treated with BAY 81-8973 from the CHESS pediatric and adult cohorts. Results: At the data cut off (May 2018), 49 patients were being treated with BAY 81-8973. The majority of pediatric patients were aged 6-11 years (51.7%, n=15), while 17.2% (n=5) were aged 0-5 years and 31% (n=9) were aged 12-17 years. In the adult US cohort, most (60%, n=12) were aged 18-35 years, 35% (n=7) were aged 36-59 years, and 5% (n=1) were aged > 60 years. The vast majority of patients across cohorts had severe disease (93.1% of children and 100% of adults); however, 89.7% (26/29) of children and 80% (16/20) of adults had no target joints. In this population, 75.9% (22/29) of children and 55.0% (11/20) of adults were receiving regular prophylaxis with BAY 81-8973. Children and adults on prophylaxis both had a mean (± SD) of 2 (± 1) infusions/week, with median (Q1; Q3) weekly doses of 84 (67; 110) and 62 (29; 144) IU/kg, respectively. Overall, 20.7% (6/29) of children and 35% (7/20) of adults treated with BAY 81-8973 had zero bleeds and mean annualized bleed rate (ABR) was 2.66 (± 2.06) in children and 1.45 (± 1) in adults; 68.9% (20/29) of children and 95.0% (19/20) of adults had experienced ≤ 3 bleeds in the previous year. There were no reports of inhibitor development in either the pediatric or adult cohorts while on BAY 81-8973. Conclusions: These observations suggest that BAY 81-8973 is an effective and well-tolerated treatment for adults and children with moderate and severe hemophilia A, with ABR < 3 in children and < 2 in adults and with many patients free from bleeds despite only 67% of patients studied receiving regular prophylaxis. These data confirm the observations from the LEOPOLD trials, suggest BAY 81-8973 provides good protection from bleeding across a range of patient types in routine clinical practice and illustrate how the established pharmacokinetic profile of BAY 81-8973 translates to clinical benefits for patients with hemophilia A. Study supported by Bayer Disclosures Hirst: Bayer: Employment. Rauchensteiner:Bayer: Employment.

scholarly journals ASPIRE Final Results Confirm Established Safety and Sustained Efficacy for Up to 4 Years of Treatment With rFVIIIFc in Previously Treated Subjects With Severe Hemophilia A

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1192-1192 ◽  
Author(s):  
Beatrice Nolan ◽  
Johnny Mahlangu ◽  
Guy Young ◽  
Barbara A Konkle ◽  
K. John Pasi ◽  
...  
Keyword(s):  
Treatment Group ◽  
Safety Profile ◽  
Treatment Duration ◽  
Research Funding ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Severe Hemophilia ◽  
Open Label ◽  
Previously Treated

Abstract Introduction: Prophylactic replacement of coagulation factor VIII (FVIII) is the standard of care in hemophilia A, given its natural mechanism of action, strict homeostatic regulation, and consistent safety profile. Recombinant FVIII Fc fusion protein (rFVIIIFc) is an extended half-life therapy that demonstrated safety and efficacy in previously treated pediatric, adolescent, and adult subjects with severe hemophilia A in the Phase 3 A-LONG and Kids A-LONG trials (NCT01181128 and NCT01458106, respectively) (Young et al, J Thromb Haemostas, 2015; Mahlangu et al, Blood, 2014). Herein, the final results are reported from ASPIRE (NCT01454739), the long-term extension trial of those 2 studies. Methods: This was an open-label, multicenter, long-term trial of previously treated subjects of all ages with severe hemophilia A. Subjects received 1 of the 4 following regimens: individualized prophylaxis (IP; rFVIIIFc 25‒60 IU/kg every 3-5 days, or twice weekly), weekly prophylaxis (WP; rFVIIIFc 65 IU/kg every 7 days), modified prophylaxis (MP; personalized dosing), or episodic treatment (ET; on-demand dosing based on bleeding episodes). Subjects <12 years of age were eligible for only IP or MP. Investigators could switch a subject's treatment group at any time; therefore, each subject may appear in >1 treatment group. The primary endpoint was development of inhibitors. Secondary endpoints included annualized bleeding rates (ABRs), joint ABRs, spontaneous joint ABRs, exposure days (ED), and factor consumption. Descriptive statistics were used for analysis. Analyses were performed separately based on parent study. Results: A total of 211 subjects (150 were from A-LONG and 61 were from Kids A-LONG) enrolled in ASPIRE, and 186 subjects (132 from A-LONG and 54 from Kids A-LONG) completed the study. Subjects from Kids A-LONG had a median (range) age of 6.0 (2-12) years. Of the subjects from the A-LONG study enrolled to ASPIRE, the median (range) age was 31.0 (13-66) years. Most subjects received IP regardless of parent study (Kids A-LONG: IP [n=59], MP [n=3]; A-LONG: IP [n=110], WP [n=27], MP [n=21], ET [n=13]). No inhibitors were observed throughout the study, and the overall safety profile of rFVIIIFc was consistent with the parent studies and prior interim analyses. ABRs remained low throughout the entirety of ASPIRE in subjects prescribed IP (Table 1). For subjects from the Kids A-LONG study, the median (range) number of ED during ASPIRE was 332.0 (18.0-467.0) days. Total median (range) treatment duration was 166.6 (14.4-203.0) weeks. The median (range) number of ED for A-LONG subjects was 267.5 (8.0-660.0) days. Total median treatment duration was 201.4 (5.1-274.6) weeks. Overall, the median (range) duration of treatment with rFVIIIFc was 4.1 (0.4, 5.9) years. From the end of the parent study to the end of ASPIRE, the rFVIIIFc dosing interval increased for 6.6% and 21.1% of subjects from Kids A-LONG and A-LONG, respectively (Table 2). There was no change in median weekly factor consumption from the end of either parent study to the end of ASPIRE. For subjects from Kids A-LONG, the median (IQR) was 0.0 (0.0‒3.2), while the median (IQR) for those from A-LONG was 0.0 (0.0‒0.0). Conclusions: Throughout up to 4 years of treatment with rFVIIIFc in the ASPIRE extension study, no inhibitors were reported, and low ABRs and extended dosing intervals were sustained. These data are consistent with the well-characterized safety profile and durable efficacy of rFVIIIFc prophylaxis in previously treated subjects of all ages with hemophilia A. Disclosures Nolan: Bayer: Research Funding; CSL Behring: Research Funding; Sobi: Research Funding. Mahlangu:Sanofi: Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Alnylam: Consultancy, Research Funding, Speakers Bureau; Bayer: Research Funding; Biogen: Research Funding, Speakers Bureau; Chugai: Consultancy; Catalyst Biosciences: Consultancy, Research Funding; Amgen: Consultancy; Biomarin: Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding. Young:Bayer: Consultancy; Bioverativ: Consultancy, Honoraria; Kedrion: Consultancy; Novo Nordisk: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Genentech/Roche: Consultancy, Honoraria; Shire: Consultancy, Honoraria. Konkle:Sangamo: Research Funding; Gilead: Consultancy; Spark: Consultancy, Research Funding; BioMarin: Consultancy; CSL Behring: Consultancy; Genentech: Consultancy; Bioverativ: Research Funding; Pfizer: Research Funding; Shire: Research Funding. Pasi:Shire: Speakers Bureau; Alnylam: Honoraria, Research Funding; Bayer: Speakers Bureau; Octapharma: Honoraria; Pfizer: Speakers Bureau; Biomarin: Honoraria, Research Funding; Sobi: Honoraria; Bioverativ: Honoraria, Research Funding; NovoNordisk: Speakers Bureau; Catalyst Bio: Honoraria; Apcintex: Honoraria. Oldenburg:Novo Nordisk: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Biogen: Honoraria, Research Funding; Shire: Honoraria, Research Funding; Grifols: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Swedish Orphan Biovitrum: Honoraria, Research Funding. Nogami:Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau. Tripkovic:Sobi: Employment. Rudin:Bioverativ: Employment, Equity Ownership.

scholarly journals A Novel Methodology for Building Longitudinal, Patient-Centric Real World Datasets in Hemophilia A

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 594-594
Author(s):  
Mark W Skinner ◽  
Gillian Hanson ◽  
Tao Xu ◽  
Richard Ofori-Asenso ◽  
Richard H. Ko ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Stock Options ◽  
Research Funding ◽  
Hemophilia A ◽  
Advisory Board ◽  
Real World Data ◽  
Advisory Committees ◽  
Patient Reported ◽  
Privately Held

Abstract Background: There are limited real-world data (RWD) available on the unmet needs of people with mild or moderate hemophilia A (PwHA). This population accounts for 40-52% of all PwHA, including nearly all women with hemophilia A (HA), and is under-represented in scientific literature (Michele, et al. Haemophilia 2014; Benson, et al. Blood Transfus 2018; Peyvandi, et al. Haemophilia 2019). Available claims data from payer databases are confined to billing codes, and lack key information on outcomes and disease characterization (e.g. severity, treatment response.) (Tyree, et al. Am J Med Qual 2006). Registry datasets can require resource-intensive data entry and potentially miss key information about care received at outside facilities, at home, or after patients switch providers (Gliklich, et al. Registries for Evaluating Patient Outcomes: A User's Guide. 2014). To address these data gaps, we developed a novel, patient-centered approach to create a longitudinal healthcare database from individuals with mild and moderate HA in the United States. This study assessed the feasibility of this approach, which integrates medical record data collected during routine clinical care along with patient-reported outcomes (PROs) to provide needed insights into this under-represented population. Methods: Recruitment began in June 2020 via a broad strategy of social media outreach, healthcare provider partnerships, and patient advocacy groups. Eligibility was confined to mild or moderate PwHA, confirmed via physician report within provider notes in combination with baseline factor VIII levels (&gt;5-50% mild, 1-5% moderate.) This study received research ethics board approval and abides by the guiding principles of the Declaration of Helsinki. PwHA enrolled via an online record management platform, PicnicHealth. After signing authorization forms for collection of their electronic health records (EHR) and informed consent to share their de-identified data for research, participants were prompted to enter information on their care providers. Records were gathered from all providers, across any facility, retrospectively as records were available. (Figure 1) All records obtained were made available to the participants via a medical timeline. Records were translated to text via optical character recognition with human review. Data elements from structured text as well as disease-specific elements from narrative text were captured using natural language processing and supervised machine learning. All elements, including visit metadata, conditions, measurements, drugs, and procedures were mapped to standardized medical ontologies and reviewed by a team of nurses. (Table 1) Quality control was assessed via inter-abstractor agreement on outputs with physician review. Patient-reported bleed, treatment, and pain data were collected via online questionnaire for a subset of PwHA, with participants prompted to enter data every 2 weeks. Abstracted EHR data was linked to PRO responses in a de-identified dataset. Cohort and abstraction characteristics were summarized descriptively. Results: From June 1, 2020 to June 30, 2021, 104 PwHA met eligibility criteria for enrollment (65 [62.5%] mild; 39 [37.5%] moderate). Participants saw providers across 34 states in the US, 22.1% (23/104) were female, and 20.6% (14/68) of those with known race/ethnicity status were from minority groups. Records were gathered from a median of six care sites and 16 providers per participant. A median of 50 (IQR [21-93]) clinical documents from 11 years were processed for each PwHA. (Table 2) Inter-abstractor agreement to assess abstraction quality averaged 95.9% for condition, 99.5% for drug name, and 95.4% for drug start date. As of June 2021, the average PRO response rate was 90.3% (150/166 of all requests) and continues prospectively. Conclusions: The patient-centric data collection methods implemented in this study provide a novel approach to build longitudinal real-world data sets. Technology-enabled data abstraction showed consistent high quality when processing the heterogeneous clinical records across disparate providers and care sites, and direct engagement with patients complements potential gaps in the clinical record. Additionally, this approach provides needed data on groups under-represented in RWD and traditional PwHA cohorts, including those with mild and moderate disease and women with HA. Figure 1 Figure 1. Disclosures Skinner: ICER: Membership on an entity's Board of Directors or advisory committees; Spark (DMC): Honoraria; Sanofi: Honoraria; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Honoraria; Pfizer (DMC): Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; uniQure: Research Funding; Takeda: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Freeline: Research Funding; BioMarin: Honoraria, Research Funding; IPA Ltd.: Current holder of individual stocks in a privately-held company; National Hemophilia Foundation: Consultancy; Institute for Policy Advancement Ltd: Current Employment; WFH USA: Membership on an entity's Board of Directors or advisory committees; BCBS MAP: Membership on an entity's Board of Directors or advisory committees. Hanson: PicnicHealth: Current Employment, Current holder of stock options in a privately-held company. Xu: F. Hoffmann-La Roche AG: Current Employment. Ofori-Asenso: F. Hoffmann-La Roche Ltd: Current Employment. Ko: Genentech, Inc.: Current Employment; Genentech, Inc.-Roche: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Cibelli: PicnicHealth: Current Employment. Nissen: Novartis: Consultancy; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment, Current holder of stock options in a privately-held company. Witkop: Roche Advisory Panel: Consultancy; National Hemophilia Foundation: Current Employment. Sanabria: F. Hoffmann-La Roche Ltd: Current Employment, Current holder of individual stocks in a privately-held company. Shapiro: Novartis: Research Funding; Novo Nordisk: Other: Advisory board fees, Research Funding, Speakers Bureau; Octapharma: Research Funding; Pfizer: Research Funding; OPKO: Research Funding; Prometric BioTherapeutics: Research Funding; Sangamo: Other: Advisory board fees, Research Funding; Sigilon Therapeutics: Other: Advisory board fees, Research Funding; Takeda: Research Funding; Kedrion Biopharma: Research Funding; Glover Blood Therapeutics: Research Funding; Genentech: Other: Advisory board fees, Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Bioverativ (a Sanofi company): Other: Advisory board fees, Research Funding; BioMarin: Research Funding; Agios: Research Funding.

The real-world experience with nivolumab in previously treated patients with advanced non small cell lung cancer (NSCLC): A Galician Lung Cancer Group clinical practice.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20564-e20564
Author(s):  
MC Areses ◽  
Rosario Garcia Campelo ◽  
Jorge García González ◽  
Francisco Javier Afonso ◽  
Martin Emilio Lazaro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Adverse Events ◽  
Real World ◽  
Advanced Nsclc ◽  
Stage Iiib ◽  
The Real ◽  
Prior Therapy ◽  
Previously Treated Patients ◽  
Previously Treated

e20564 Background: Nivolumab, was the first checkpoint inhibitor to show a survival benefit in previously treated patients with advanced NSCLC in two randomized trials (CheckMate 017 and 057). Experience in routine clinical practice may differ from that seen in a controlled clinical trial. This is an observational study that represents the real-world experience. Methods: Elegibility criteria included, histologically confirmed NSCLC stage IIIB vs IV, evaluable disease and at least one prior therapy. Patients received nivolumab 3 mg/kg IV (60 min) every 2 weeks until progressive disease or unacceptable toxicity. The aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The exploratory assessments include response rate (RR), progression-free survival (PFS), overall survival (OS) and treatment related adverse events (AEs). Results: From August 2015 to January 2017, with a median follow time of 18 months, 188 patients were enrolled from 9 different centers. Patients demographics were: median age 62 years, 44 female and 144 male; 17 never smoker and 171 former or current smoker; 105 adenocarcinoma, 7 large-cell carcinoma, 66 squamous, 3 adenosquamous and 7 NSCLC; 61 stage IIIB and 129 stage IV; 42 with central nervous system metastasis; and 70 received 2 or more prior therapy lines. Among 156 patients evaluated, 1,3% had CR, 28,2% PR, 29,7% SD and 40,8% PD. At the time of database lock, the median of PFS was 2.9 IC 95% (2,3-3.4) and OS was 12,8 IC 95% (9,2-16,4). The evaluation of PFS and OS by baseline characteristics doesn´t revealed statistical significance. Grade 1-2 treatment related adverse events (AEs) occurred in 58% of the patients: asthenia (22%), rash (14%), diarrhea (8%), anorexia (7%), endocrine (6%) and neumonitis (1,5%). Grade 3-4 AEs occurred in 5 patients; (3) diarrhea and (2) neumonitis and there were 3 treatment-related deaths. Conclusions: This study represents the real-word experience with nivolumab and the results are consistent with those previously reported in the CheckMate 017 and 057 trials.

scholarly journals Real-World Clinical Management of Patients with Hemophilia and Inhibitors: Effectiveness and Safety of aPCC in Patients with >18 Months' Follow-up in the FEIBA Global Outcome Study (FEIBA GO)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2418-2418
Author(s):  
Jerzy Windyga ◽  
Pal A Holme ◽  
C. Hermans ◽  
Ana R Cid ◽  
Nirjhar Chatterjee ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Hemophilia A ◽  
Outcome Study ◽  
Employment Equity ◽  
Bleeding Rate ◽  
Patient Consent ◽  
Equity Ownership

Introduction: The primary objective of the FEIBA Global Outcome study (FEIBA GO) is to describe the long-term, real-world effectiveness and safety of activated prothrombin complex concentrate (aPCC; Feiba®, Baxalta Inc, a Takeda company, Lexington, MA, USA) for preventing and managing bleeding in patients with congenital hemophilia A or B with inhibitors (PwHI) across different clinical settings. This interim >18-month analysis corresponds to the report of May 2019. Methods: FEIBA GO (EUPAS6691) is an ongoing post-authorization, prospective, observational, multicenter cohort study. Male PwHI diagnosed before study entry and prescribed treatment with aPCC will be followed over 4 years; treatment regimens are prescribed at the physician's discretion. Ethics approval and patient consent were obtained. Results: Enrollment was completed on December 31, 2017, with 53 PwHI from 27 sites in 11 countries (hemophilia A: n=52, hemophilia B: n=1; median [range] age at baseline: 18 [2-71] years). Total annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) for all bleeds are shown in Table 1 for the 21 patients who received prophylaxis or on-demand aPCC and had >18 months of follow-up data. Of 15 patients who received aPCC prophylaxis, 4 (26.7%) and 7 (46.7%) reported ABRs of ≤3 and AJBRs of ≤3, respectively. All 53 enrolled patients were included in the safety analysis. During the >18 month analysis period, a total of 139 non-serious treatment-emergent adverse events (TEAEs) were reported in 29 of 53 patients (including 9 events in 3 patients probably related to treatment and 2 events in 1 patient possibly related), and 40 serious TEAEs were reported in 17 patients. One possibly related serious TEAE of acute myocardial posterior wall infarction with embolic right coronary artery occlusion was reported in a patient with a catheter port; outcome: recovered/resolved. No thrombotic microangiopathies were reported. Conclusions: This interim analysis of real-world data at >18 months' follow-up is consistent with experience and continues to validate the safety and effectiveness of aPCC. Long-term follow-up data over 4 years from FEIBA GO will provide further information on the real-world effectiveness and safety of aPCC as monotherapy. Disclosures Windyga: Rigel Pharmaceuticals: Honoraria, Research Funding; Werfen: Honoraria, Research Funding; Baxalta/Shire (a Takeda company): Honoraria, Research Funding; Ferring Pharmaceuticals: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Alnylam: Honoraria, Research Funding; Siemens: Honoraria, Research Funding; Sobi: Honoraria, Research Funding. Holme:Sobi: Honoraria, Research Funding; Shire, a Takeda company: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; CSL Behring: Honoraria; Bayer: Honoraria, Research Funding; Octapharma: Research Funding; Novo Nordisk: Honoraria. Hermans:Shire, a Takeda company: Consultancy; Novo Nordisk: Consultancy. Cid:Novo Nordisk: Honoraria; Shire, a Takeda company: Honoraria. Chatterjee:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Jiang:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Cano-Garcia:Shire, a Takeda company: Employment, Equity Ownership. Escuriola:Octapharma: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Kedrion: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; Shire, a Takeda company: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding.

scholarly journals Efficacy and Safety Results from a Phase 3b, Open-Label, Multicenter, Continuation Study of Rurioctocog Alfa Pegol for Prophylaxis in Previously Treated Patients with Severe Hemophilia A

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2483-2483 ◽  
Author(s):  
Eric S. Mullins ◽  
Barbara A Konkle ◽  
Catherine E. McGuinn ◽  
Werner Engl ◽  
Srilatha D. Tangada
Keyword(s):  
Half Life ◽  
Research Funding ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Open Label ◽  
Advisory Committees ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Equity Ownership ◽  
Recombinant Fviii

Abstract Background: Patients with severe hemophilia A experience substantial morbidity and mortality due to frequent spontaneous and traumatic bleeding episodes, especially in joints. Prophylaxis with standard half-life factor VIII (FVIII) is the standard of care to prevent bleeds. Extended half-life products benefit patients by reducing the number of infusions without impacting the treatment efficacy. Methods: This phase 3b, prospective, open-label, multicenter, continuation study (NCT# 01945593) investigated the safety and efficacy of a PEGylated recombinant FVIII with an extended half-life, rurioctocog alfa pegol (SHP660, BAX 855, ADYNOVATE®, Shire, Lexington, MA, USA), for prophylaxis and treatment of bleeding in patients with severe hemophilia A (FVIII <1%). Eligible children and adults were ≤75 years of age and had either completed a previous rurioctocog alfa pegol study (NCT# 01599819, 01736475, 02210091, 02615691, 01913405, or 02585960) and were willing to immediately transition to the continuation study, or were naïve to rurioctocog alfa pegol but had received treatment with plasma-derived or recombinant FVIII for ≥150 (in patients ≥6 years of age) or ≥50 (in patients <6 years of age) exposure days. Patients received prophylactic rurioctocog alfa pegol at least twice weekly, either at a fixed dose (FD; 45 ± 5 IU/kg in patients ≥12 years of age; 50 ± 10 IU/kg in those <12 years of age; dose adjustment ≤80 ± 5 IU/kg allowed) or with pharmacokinetically (PK)-tailored dosing (≤80 ± 5 IU/kg) to maintain FVIII trough levels ≥3%. The co-primary endpoints assessed were the incidence of FVIII inhibitory antibody development (as measured by ≥0.6 BU in the Nijmegen modification of the Bethesda assay) and the spontaneous annualized bleed rate (ABR). Secondary endpoints included overall hemostatic efficacy ratings and occurrence of adverse events (AEs). Results: The study began in October 2013 and completed in March 2018. Overall, 216 patients receiving prophylaxis were eligible and included in the safety/full analysis dataset (≥1 dose received). Of these, 215 were male, the mean (SD) age at enrollment was 22.8 (15.7) years, the mean (SD) number of documented previous rurioctocog alfa pegol exposure days was 57.0 (39.6), the total ABR over 3-6 months prior to enrollment in the continuation study (including patients naïve to rurioctocog alfa pegol or receiving on-demand or prophylactic treatment with rurioctocog alfa pegol) was mean (SD) 4.7 (12.6), median (range) 0.0 (0-69). Most patients (206; 95.4%) had participated in a previous rurioctocog alfa pegol study. Overall, 215 patients received ≥1 dose in the FD regimen and 25 received ≥1 dose in the PK regimen. These patients received a mean (SD) of 1.72 (0.29) and 2.11 (0.61) prophylactic infusions per week, respectively, with a mean (SD) dose per infusion of 51.15 (8.11) IU/kg and 52.14 (17.03) IU/kg, respectively. None of the patients developed a confirmed FVIII inhibitor in this study and only 1 treatment-related allergic or hypersensitivity reaction (a nonserious mild AE) was reported. Nonserious AEs assessed by the investigators to be related to treatment occurred in 11/216 (5.1%) patients. Serious AEs (SAEs) occurred in 33 (15.3%) patients; there were no SAEs assessed by the investigators to be related to treatment. Descriptive statistics on spontaneous, joint, and total ABR by prophylactic regimen are shown in the Table. The overall total ABR in all patients was mean (SD) 2.5 (3.1), median (range) 1.6 (0.0-19.5). Overall hemostatic efficacy was rated as good or excellent in 88.5% of all bleeds and 89.4% of all bleeds were treated with 1 or 2 infusions. Conclusions: These results show that in previously treated patients with severe hemophilia A, rurioctocog alfa pegol prophylaxis in FD- and PK-tailored regimens was well tolerated and effective. None of the patients developed FVIII inhibitory antibodies, and a decrease in mean total ABR was reported in these patients compared with baseline. Disclosures Mullins: Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees. Konkle:Genentech: Consultancy; CSL Behring: Consultancy; Gilead: Consultancy; Pfizer: Research Funding; Spark: Consultancy, Research Funding; BioMarin: Consultancy; Bioverativ: Research Funding; Shire: Research Funding; Sangamo: Research Funding. McGuinn:CSL Behring: Consultancy; BioMarin: Consultancy; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spark: Consultancy, Research Funding; Genentech: Consultancy; Shire: Research Funding; Pfizer: Research Funding. Engl:Shire: Employment, Equity Ownership. Tangada:Shire: Employment, Equity Ownership.

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