scholarly journals Perception of Actual Factor Concentrates and Expectations Towards Future Treatment with New Long-Lasting Products - Results of a Survey Among Haemophilia Patients in Germany - Analysis of Open Questions

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3269-3269
Author(s):  
Werner Kalnins ◽  
Wolfgang A. Miesbach ◽  
Sylvia von Mackensen
Keyword(s):  
Half Life ◽  
New Products ◽  
Severe Form ◽  
Postal Survey ◽  
Patient Organisation ◽  
Haemophilia A ◽  
Additional Information ◽  
German Patient ◽  
Open Questions ◽  
Actual Factor

Abstract Background: Prophylactic treatment allows patients with haemophilia (PWH) to live an approximately normal life. The majority of German PWH receive prophylaxis. The need of frequent weekly injections may impact negatively treatment adherence. This is the expected reason which might result in increased annual bleeding rate. Therefore there is a need for half-life extended products which will be launched end of this year in Germany. However, little is known about patients' perspectives on the use of new products with extended half-life and their willingness to switch to these products. Aim: The German patient organisation DHG is interested to better understand PWH's expectations and concerns towards these new products in order to adapt their support for the haemophilia community. Methods: The study consisted of two phases: 1) conduct of separate focus groups with adult haemophilia patients and parents of haemophilic children with respect to the new long-lasting products across Germany; 2) based on the focus group results construction of a questionnaire for a systematic postal survey among DHG members with haemophilia A or B (n=1,499). Results: The postal survey included questions concerning haemophilia, knowledge about half-life of actual factor concentrates (FC) and attitudes towards actual FC and open ended questions concerning the expectations towards new products and how therapy could be facilitated. The open ended questions should give the participants the chance to write down other aspects, problems, laments and other wishes. Several aspects could be mentioned by the same subject. Out of the sent 1,499 questionnaires 697 questionnaires were sent back; mainly from adult patients (n=518), 177 from parents of haemophilic children. Patients had haemophilia A (83.7%), in a severe form (77.8%), were on prophylaxis (61.4%), mostly three times a week (47.8%) and used recombinant products (57.8%). 14.1% have had an inhibitor. Open questions were answered by 462 respondents, at least 1 to maximum 5 aspects were mentioned. Open questions on the current situation ["facilitation of therapy"] (n=302): less packaging waste (n=129), no cooling required (n=61), sc injections/oral medication/nasal medication (n=54), better supplies like perfect injection needle etc. (n=27), prefilled syringe (n=25), diversity of package size (125 iU to 4000 iU) (n=24), support in home care therapy (n=17), simpler treatment documentation (n=9), improved logistic/delivery for home treatment (n=8). Open questions for future situation (n=160) ["expectations towards new long-lasting products"]: less injections (n=492), same safety/efficacy/compatibility (n=44), better quality of life (n=22), no fridge (n=16), treatment costs/reduction-no increase (n=15), higher trough level (n=9), smaller packaging (n=8), easier handling (n=8), and many more mentioned 1- 3 times. Conclusions: The answers to the open questions in this representative survey among German haemophilia patients and parents of children with haemophilia provide important additional information and insights in the unmet needs of haemophilia patients, which will help the German patient association and pharmaceutical companies to better inform patients about the new up-coming products taking patients needs into consideration. Disclosures Kalnins: SOBI: Consultancy. Miesbach:SOBI: Consultancy. von Mackensen:SOBI: Consultancy.

scholarly journals Perception of Actual Factor Concentrates and Expectations Towards Future Treatment with New Long-Lasting Products - Results of a Survey Among Haemophilia Patients in Germany

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4449-4449
Author(s):  
Sylvia von Mackensen ◽  
Struck Heinrich ◽  
Werner Kalnins ◽  
Johannes Oldenburg
Keyword(s):  
Side Effects ◽  
Focus Groups ◽  
Half Life ◽  
New Products ◽  
Storage Conditions ◽  
Postal Survey ◽  
Patient Organisation ◽  
Haemophilia A ◽  
Two Phases ◽  
Actual Factor

Abstract Background: Prophylactic treatment allows patients with haemophilia (PWH) to live a normal life, however the need of frequent weekly injections may impact negatively treatment adherence which might result in increased annual bleeding rate and impaired quality of life. Therefore there is a need for half-life extended products which will be launched in the next years. However, little is known about patients' perspectives on the use of new products with extended half-life and their willingness to switch to these products. Aim: The German patient organisation DHG is interested to better understand PWH's expectations and concerns towards these new products in order to adapt their support for the haemophilia community. Methods: The study consisted of two phases: 1) conduct of separate focus groups with adult haemophilia patients and parents of haemophilic children with respect to the new long-lasting products across Germany; 2) based on the focus group results construction of a questionnaire for a systematic postal survey among DHG members with haemophilia A or B (n=1,499). Results: The postal survey included questions concerning haemophilia, knowledge about half-life of factor concentrates and attitudes towards factor concentrates (FC). In total 697 questionnaires were sent back (46.5%); 518 patients and 177 parents of haemophilic children. The majority of patients had haemophilia A (83.7%), were severely affected (77.8%), received prophylaxis (61.4%), mostly three times a week (47.8%) and used recombinant products (57.8%). 14.1% had a history of an inhibitor. Most of the patients and parents did not know the correct half-life of the actual FC [FVIII: 30.1%, FIX: 74.5%]. In general they were satisfied (M=4.4±0.8) with their actual FC; only 4.1% were unsatisfied, mainly with short half-life, difficult manageability and need to store it in the fridge. They expected from the new products to have prolonged half-life, better stability, better transparency concerning production of the FC and improved manageability. 59% would be willing to switch to new products if they have a prolonged half-life, provide more security when travelling and have the same safety of the actual FC. Reasons for not willing to switch were fear of inhibitors and uncertain safety of new product as well as satisfaction and no side effects of actual FC. They have almost no information about the new up-coming products, wish more information about half-life, possible side-effects and efficacy and would consider changing product if the prolongation of the half-life is at least double as high as the actual FC. The majority wants to receive information about new products from their haemophilia treater (79%), leaflets/newsletter of DHG (77%) and information letter from HTC/DHG (32%). Analyses between clinical subgroups showed significant differences for knowledge of half-life of FVIII for type of haemophilia (p<.0001), severity (p<.0001), treatment (p<.0001) and age (p<.031). Significantly more patients on prophylaxis would be willing to switch to new products because of their prolonged half-life (92%; p<.0001) and benefits for doing sports (53%, p<.0001), while on-demand patients would do so because of their longer stability outside the fridge (69%; p<.0001), advantages for surgeries (68%; p<.0001), easier application (44%; p<.001) and 24% would be motivated to switch to prophylaxis. No differences were found for satisfaction with actual FC and the willingness to switch to new products. Presence of inhibitors did not have an impact. In the five focus groups 23 adult haemophilia patients (78.3% HA; 78.3% severely affected) and 9 parents of haemophilic children (88.9% HA; 77.8% severely affected) were interviewed (Hamburg, Cologne, Munich, 2x Dresden). Conclusions: In this representative survey among German patients and parents of children with haemophilia they reported to be satisfied with their actual FC. Nevertheless, unsatisfactory aspects of their actual FC are half-life, manageability and storage conditions. The majority did not have a lot of information of the new long-lasting products, but would be willing to switch from the actual FC to these products assuming the half-life is prolonged and has the same safety of the actual FC. These findings will help patient associations and pharmaceutical companies to better inform patients about the new up-coming products taking patients needs into consideration. Disclosures von Mackensen: SOBI: Consultancy. Heinrich:SOBI: Consultancy. Kalnins:SOBI: Consultancy. Oldenburg:SOBI: Consultancy.

scholarly journals Expectations and Concerns Towards New Extended Half-Life (EHL) Products - Results of Surveys Among Haemophilia Patients from the Dach Region

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4740-4740
Author(s):  
Sylvia von Mackensen ◽  
Werner Kalnins ◽  
Hostettler Lino ◽  
Krucker Joerg ◽  
Manuela Albisetti ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Half Life ◽  
Research Funding ◽  
New Products ◽  
Postal Survey ◽  
Haemophilia A ◽  
Actual Factor ◽  
Life Prolongation

Abstract Background: In Western Europe most patients with haemophilia (PWH) have the opportunity to get regular prophylaxis and can life normal lives due to the availability and funding of factor concentrates. The majority of haemophilia patients have to inject themselves every other day or three times a week.The need of frequent injections may impact negatively patients' treatment adherence which might result in increased annual bleeding rate and impaired quality of life. Therefore there is a need for half-life extended (EHL) products which will be launched in the next years in Europe for treatment of haemophilia A and B and are expected to improve patients' quality of life. However, little is known about patients' perspectives on the use of these new EHL products and their willingness to switch to these products. Aim: National Member Organisations (NMO) of haemophilia patients from the DACH Region (D=Germany, A=Austria, CH=Switzerland) were interested to better understand PWH's expectations and concerns towards these new EHL products in order to adapt haemophilia treatment to real patients' needs. Methods: A systematic postal survey was sent out to 2,644 patients and parents of children with haemophilia A or B in Germany (2015), Switzerland (2016) and Austria (2016). The postal survey included questions concerning demographic and clinical data of the patient, knowledge about half-life of actual factor concentrates (FC) and attitudes towards FC in terms of satisfaction with actual factor concentrate, expectation towards new EHL products, willingness to switch to new EHL products, required information for decision making, preferred information sources and facilitation of therapy in general. Results: In total 1,013 questionnaires were sent back (38.3%); 2 patients had to be excluded from further analysis since these patients had VWD. 747 adult haemophilia patients and 262 parents of haemophilic children participated, 2 respondents could not be classified. The majority of patients had haemophilia A (84.1%), were severely affected (73%), received prophylaxis (56.6%), mostly three times a week (40.9%) and used recombinant products (59.4%). 14% had a history of an inhibitor (past, actual). Most of the patients and parents did not know the correct half-life of the actual FC [FVIII: 30%, FIX: 75%]. In general they were satisfied (M=4.4±0.8) with their actual FC; only 4.1% were unsatisfied, mainly with difficult manageability and short half-life of FC. They expected from the new products to provide less frequent injections, better efficacy and safety/no side effects. 59.6% would be willing to switch to new products if they have a prolonged half-life and have the same safety of the actual FC. Reasons for not willing to switch were fear of inhibitor development and no side effects of actual FC. They had almost no information about the new up-coming products, wish more information about half-life, possible side-effects and efficacy and would consider changing product if the prolongation of the half-life is at least double as high as the actual FC. 20.6% would switch already with a half-life prolongation of 1.2-1.5 times longer; 3.3% would not switch at all. The majority wanted to receive information about new products from their haemophilia treater (77.1%), newsletter of their NMO (73.4%) and information letter from their HTC/NMO (35.7%). They would wish smaller packages, different mode of administration and better manageability of the product in order to facilitate their therapy. There was a significant difference across countries regarding treatment regimen (p<.0001) and used product category (p<.0001); in Germany more patients were on prophylaxis (71.3%) and in Switzerland more patients used recombinant products (75.8%). No differences were found for the satisfaction with their actual product, their willingness to switch to new EHL products in general and the time of required half-life prolongation. In Switzerland more patients required information on costs of the new EHL products for an adequate decision making process for switching (p<.0001). Conclusions: In this representative survey among patients and parents of children with haemophilia of the DACH Region it could be shown that even though they were generally satisfied with their actual FC the majority would be willing to switch from their actual FC to the new up-coming EHL products assuming the half-life is prolonged and has the same safety of the actual FC. Disclosures von Mackensen: Shire: Research Funding; SOBI: Research Funding. Kalnins:SOBI: Research Funding. Lino:SOBI: Research Funding. Joerg:SOBI: Research Funding. Albisetti:Boehringer Ingelheim: Other: Pediatric Expert Working Group. Weiss:Shire: Research Funding.

Continuous infusion of extended half-life factor VIII (efmoroctocog alpha) for surgery in severe haemophilia A

Haemophilia ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. e280-e283
Author(s):  
I. C. L. Kremer Hovinga ◽  
R. E. G. Schutgens ◽  
P. R. van der Valk ◽  
L. F. D. van Vulpen ◽  
E. P. Mauser-Bunschoten ◽  
...  
Keyword(s):  
Factor Viii ◽  
Continuous Infusion ◽  
Half Life ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Life Factor

scholarly journals 5PSQ-010 Benefits provided by recombinant long half-life coagulation factors in patients with severe haemophilia ‘A’ in prophylaxis

2020 ◽  
Author(s):  
N Blazquez-Ramos ◽  
JA Romero Garrido ◽  
C Bilbao Gómez-Martino ◽  
C Sobrino Jiménez ◽  
M Moreno Palomino ◽  
...  
Keyword(s):  
Half Life ◽  
Coagulation Factors ◽  
Haemophilia A ◽  
Severe Haemophilia

F8 genetic analysis strategies when standard approaches fail

2014 ◽  
Vol 34 (02) ◽  
pp. 167-173 ◽  
Author(s):  
B. Pezeshkpoor ◽  
A. Pavlova ◽  
J. Oldenburg ◽  
O. El-Maarri
Keyword(s):  
Genetic Analysis ◽  
Half Life ◽  
Untranslated Region ◽  
Mutation Screening ◽  
Screening Methods ◽  
Haemophilia A ◽  
Splice Sites ◽  
Coding Region ◽  
Coding Regions ◽  
Analysis Strategies

SummaryHaemophilia A is a common X-linked recessive disorder caused by mutations in F8 leading to deficiency or dysfunction of coagulant factor VIII (FVIII). Despite tremendous improvements in mutation screening methods, in a small group of patients with FVIII deficiency suffering from haemophilia A, no DNA change can be found. In these patients, analysis reveals no causal mutations even after sequencing the whole coding region of F8 including the flanking splice sites, as well as the promoter and the 3’ untranslated region (UTR). After excluding the mutations mimicking the haemophilia A phenotype in interacting partners of the FVIII protein affecting the half life and transport of the protein, mutations or rearrangements in non-coding regions of F8 have to be considered responsible for the haemophilia A phenotype.In this review, we present the experiences with molecular diagnosis of such cases and approaches to be applied for mutation negative patients.

Pharmacokinetics, Coagulation Factor Consumption, and Product Efficacy in Patients Crossing Over from Full-Length FVIII to B-Domain Deleted R-FVIII and Back to Full-Length FVIII.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2269-2269
Author(s):  
Catherine J Rea ◽  
Alex Dunkerley ◽  
Benny Sorensen ◽  
Savita Rangarajan
Keyword(s):  
Clinical Efficacy ◽  
Half Life ◽  
Coagulation Factor ◽  
Outcome Data ◽  
Full Length ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Efficacy And Safety ◽  
Significant Difference ◽  
Recovery Times

Abstract Introduction: Treatment with B-domain deleted recombinant factor VIII (BDD-rFVIII) has proven to be effective and safe both in clinical trials and post marketing surveillance studies. However, intermittent concerns have been raised regarding the pharmacokinetic performance, efficacy and incidence of inhibitor formation with the BDD-rFVIII product. Aims: The objective of the present study was to perform a retrospective survey of half-life measurements, clinical efficacy and safety in patients with severe Haemophilia A, when switching treatment from full-length FVIII (FL-FVIII) to BDD- rFVIII and then back to full-length FVIII. We hypothesized that the biological half-life of FVIII would be equal regardless of the product used. Furthermore, we hypothesized that the total factor consumption and bleeding frequency would be indistinguishable irrespective of product used. Finally, we report on safety as evaluated by development of inhibitors and clinical outcome following surgery. Methods: Patients treated with BDD-rFVIII (between 1998 and 2008) were identified from an in-house database. Data collected included annual half-life (T/2) and recovery times (K values), total coagulation factor consumption, and number of bleeds per year as measures of clinical efficacy. Safety data consisted of surgical outcome data and incidence of inhibitor formation. The information was extracted from electronic databases and verified by a review of patients’ clinical notes. The outcome data was non-parametric, hence, paired analysis was performed using Wilcoxon signed rank test and Friedman ANOVA. Data is given as a median value and range. P-value &lt; 0.05 was set as level of statistical significance. Results: In total, 70 patients received BDD-rFVIII on at least one occasion. Following a specified list of criteria, evaluable data was obtainable for 15 males, all with verified severe Haemophilia A (FVIII:C &lt;1%). The average age was 10.2 years (median 10, range 4–17). The median duration on BDD-rFVIII was 30 months (range 20–54). Using the one-way non-parametric ANOVA, no statistically significant difference was detected between the half-life and recovery times recorded during the switch from FL-FVIII (T/2 median 9.15 hours, range 6.4–22; K median 2.7, range 2.0–3.4) to BDD-rFVIII (T/2 median 9.7, range 4.7–16.8; K median 1.8, range 1.0–3.5) and back to FL-FVIII (T/2 median 9.0, range 5.0–19.5; K median 2.0, range 1.6–2.8). Furthermore, there was no significant difference in coagulation factor usage (BDD-rFVIII median 4803 iu/kg/year, range 659–11304; FL-FVIII median 5349, range 1691–10146), nor number of reported bleeds (BDDrFVIII median 6, range 0–24; FL-FVIII median 5.0, range 0–17). None of the 15 patients developed an inhibitor on BDD-rFVIII. Of the total 70 patients, 11 received BDD-rFVIII to cover surgical procedures (8 minor, 3 major interventions). There were no reports of excess bleeding. Conclusions: In this retrospective survey, BDD-rFVIII was found to be equivalent to other FVIII products in terms of half-life measurements, clinical efficacy and safety.

Factor VIII-Fc Fusion Protein Shows Extended Half-Life and Hemostatic Activity in Hemophilia A Dogs.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 545-545 ◽  
Author(s):  
Jennifer A Dumont ◽  
George D Kamphaus ◽  
Cara Fraley ◽  
Tamera Ashworth ◽  
Helen Franck ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Viii ◽  
Half Life ◽  
Hemophilia A ◽  
Specific Activity ◽  
Clinical Signs ◽  
Severe Form ◽  
Activity Data ◽  
Hemostatic Activity ◽  
Elisa Data

Abstract Abstract 545 A recombinant B-domain-deleted factor VIII-Fc (rFVIIIFc) fusion protein was created as an approach to extend the half-life of FVIII. The pharmacokinetics and pharmacodynamics of rFVIIIFc were evaluated in the Chapel Hill colony of hemophilia A dogs. These dogs have a severe hemophilic phenotype comparable to the severe form of human disease with F.VIII < 1%. A single intravenous dose (125 IU/kg) was administered to four dogs and immediately corrected the clotting to normal as measured by whole blood clotting time (WBCT) and aPTT. The WBCT remained below 20 min, the time consistent with FVIII:C > 1%, through approximately 96 h. The range of WBCT in our normal dogs is 8 to 12 min. The concentration of rFVIIIFc in the plasma was measured by ELISA and the terminal half-life was 15.7 ± 1.7 hr. Similar results were obtained when rFVIIIFc was measured using a FVIII-specific chromogenic activity assay (half-life was 15.4 ± 0.3 hr). The concentration vs. time curves were similar using both methods. The activity data were converted to ng/mL using the specific activity of the test article that was used to dose the animals, and these data correlated well with the ELISA data, thus demonstrating that the protein that was measured by ELISA was fully active. Two of the dogs also received a single dose of recombinant B-domain deleted FVIII (rBDD-FVIII, ReFacto®), 114 IU/kg for one dog and 120 IU/kg rBDD-FVIII for the other, and then received rFVIIIFc (125 IU/kg) 72 hr later in a cross over design. Clotting was corrected to normal immediately after dosing with both rBDD-FVIII and rFVIIIFc (determined by WBCT and clotting activity measured using an aPTT assay). However, the WBCT normalization after rFVIIIFc lasted for approximately twice as long compared to rBDD-FVIII and the half-lives determined from the ELISA data for FVIIIFc (15.7 ± 1.7 hr) were twice those determined for rBDD-FVIII (7.0 hr and 6.7 hr). No adverse clinical signs were detected with any of the infusions. Therefore construction of an Fc fusion of FVIII produces a molecule with a defined mechanism of action that has an increased half life and the potential to provide prolonged protection from bleeding. Disclosures: Dumont: Biogen Idec (Syntonix Subsidiary): Employment. Kamphaus:Biogen Idec (Syntonix Subsidiary): Employment. Fraley:Biogen Idec/Syntonix Subsidiary: Employment. Ashworth:Biogen Idec (Syntonix Subsidiary): Employment. Bitonti:Biogen Idec/Syntonix Subsidiary: Employment.

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