Could there be more

FAQs - New Developments in Haemophilia

Yes, you do have a choice. But doctors in the UK have guidelines that they have to follow and in most cases, any treatment you ask for has to come within the guidelines in order for you to have it. The guidelines are produced by NHS England. Prescribing in Wales and Northern Ireland generally follows the same guidelines. Scotland have their own guideline process but it’s unusual for them to differ very much from the NHS England guidelines.

The way these ‘commissioning guidelines’ work is quite complicated. They cover the ‘commissioning’ of treatments within the NHS. In this sense, commissioning really means what the NHS is prepared to pay for.

The guidelines are built around evidence that treatments work, of course. But they also allow for different brands of the same treatments to be made available.  Currently there are three main brands that are provided to around 7 out of 10 patients. (So it makes up 70% of the prescriptions issued for a type of treatment for haemophilia A, for instance.) Other brands make up the rest.

Overall, the guidelines cover 8 out of 10 prescriptions for a given medical condition. So, there is scope for 2 out of every 10 patients to receive treatments that aren’t covered by the commissioning guidelines. Generally, treatments that aren’t within the commissioning guidelines are much more expensive.

Most people with severe haemophilia in the UK are on standard factor VIII or IX replacement, either on prophylaxis or on-demand treatment. Now there are the newer ‘extended half-life’ (EHL) factor VIII and IX available. There is a separate commissioning guideline covering these and it’s very strict. Basically, overall your treatment has to cost the same on EHL as it would on standard factor replacement. The guidelines are built around evidence that treatments work, of course. But they also allow for different brands of the same treatments to be made available.  Currently there are three main brands that are provided to around 7 out of 10 patients. (So it makes up 70% of the prescriptions issued for a type of treatment for haemophilia A, for instance.) Other brands make up the rest.49 In practice, it’s become more difficult to switch to EHL factor because standard factor is cheaper than it used to be.

Treatments for haemophilia have developed a lot in the past few years. The mainstay of current treatment are clotting factors manufactured without blood donation. Now, a variation of these clotting factors, called extended half-life (EHL) factors are available.50,51,52 The half-life is a measure of how long the clotting factor lasts in your blood stream. EHL factors stay in the blood for longer so people with haemophilia can have the treatment they need to prevent bleeds (prophylaxis) less often.27, 24 With haemophilia A, you may be able to cut down from injections three times a week to twice a week.27 With haemophilia B, you may be able to cut down from twice a week to weekly or even fortnightly injections.24

A treatment that is talked about a lot is gene therapy. This is still in research but is potentially exciting because it could provide a permanent treatment for haemophilia.53 In theory, a single treatment could deliver the gene for making the missing factor and mean that people with haemophilia no longer need factor replacement.53 There are clinical trials underway for gene therapy for both haemophilia A and B.54,55,56

Finally, a new approach to haemophilia treatment is in research. Normally, clotting in the body is held in balance by factors that promote blood clotting and factors that prevent it. Haemophilia researchers have been looking into blocking proteins in the body that normally prevent blood clotting, instead of promoting clotting with injections of factor VIII (8) and factor IX (9).  One of these treatments blocks a body protein called anti-thrombin that stops the blood from clotting.57 You have the treatment as an injection under the skin (subcutaneously) once a month. Early research results have shown a drop in bleeding rates and trials are now comparing it to treatment with factor VIII (8) and IX (9).58

Another similar treatment called anti-TFPI is now being tested. TFPIs (tissue factor pathway inhibitors) are proteins that stop the blood clotting and early research has shown that blocking them in people with haemophilia can help the blood to clot.59 Two anti-TFPI treatments in research can be used for either haemophilia A and haemophilia B and are being tested in people with and without inhibitors.60, 61, 62 As with anti-thrombin, you can have them as injections under the skin (subcutaneously). They are being tested in people who normally have prophylaxis and in those who prefer on-demand treatment.61, 62

Timeline

There is a risk of side effects with any drug.

During their development, all new drugs are monitored very closely for any side effects or safety concerns. The earliest phase of testing takes place in laboratories and it is only after a potential treatment is thought to be safe that it is tested in people. The first round of clinical trials is only designed to test safety. To start with a small number of patients are given a very small dose of the test drug. The dose is gradually increased as more patients join the trial, with all participants being very closely monitored for any problems. This monitoring continues right through the clinical trial process until a treatment is licensed and made available. Even after a drug is put on the market, any reaction or symptom a patient has that could possibly be drug related has to be recorded and reported.

Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.1 What is haemophilia?). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

2 National Organization for Rare Disorders. Hemophilia A. https://rarediseases.org/rare-diseases/hemophilia-a/. Accessed 22nd August 2018

3 National Organization for Rare Disorders. Hemophilia B. https://rarediseases.org/rare-diseases/hemophilia-b/. Accessed 22nd August 2018

4 UK National Haemophilia Database. UK Bleeding Disorder Statistics for April 2016 to March 2017. http://www.ukhcdo.org/wp-content/uploads/2018/02/Bleeding-Disorder-Statistics-for-April-2016-to-March-2017-for-UKHCDO.pdf. Accessed 5th November 2018

5 World Federation of Hemophilia. How do you get haemophilia? https://www.wfh.org/en/page.aspx?pid=644. Accessed 22nd August 2018

6 World Federation of Hemophilia. Carriers and women with haemophilia. https://www.wfh.org/en/abd/carriers/carriers-and-women-with-hemophilia-en. Accessed 22nd August 2018

7 World Federation of Hemophilia. Inheritance of haemophilia. https://www.wfh.org/en/abd/carriers/carriers-inheritance-of-hemophilia-en. Accessed 5th November 2018

8 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/aetiology. Last updated April 2017. Accessed 22nd August 2018

9 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/diagnosis-approach. Last updated April 2017. Accessed 22nd August 2018

10 World Federation of Hemophilia. Carriers and women with haemophilia. https://www.wfh.org/en/abd/carriers/carriers-and-women-with-hemophilia-en. Accessed 22nd August 2018

11 NHS. Causes Haemophlia. https://www.nhs.uk/conditions/haemophilia/causes/. Accessed 22nd August 2018

12 NHS. Symptoms Haemophilia. https://www.nhs.uk/conditions/haemophilia/symptoms/. Accessed 22nd August 2018

13 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.4 Fitness and physical activity). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

14 The Haemophilia Society. What to expect from your treatment centre. http://haemophilia.org.uk/bleeding-disorders/treatment-centres/expectations-treatment-centre/. Accessed 22nd August 2018

15 Haemnet. Haemophilia Nursing. https://www.haemnet.com/external/care/haemophilia-nursing. Accessed 22nd August 2018

16 Haemnet. Haemophilia Physiotherapy. https://www.haemnet.com/external/care/haemphilia-physiotherapy. Accessed 22nd August 2018

17 NHS. Treatment. https://www.nhs.uk/conditions/haemophilia/treatment/ Last updated April 2017. Accessed 22nd August 2018

18 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/prevention. Last updated April 2017. Accessed 22nd August 2018

19 Valentino LA1, Ewenstein B, Navickis RJ, Wilkes MM. Haemophilia. Central venous access devices in haemophilia. 2004 Mar;10(2):134-46. https://www.ncbi.nlm.nih.gov/pubmed/14962202 . Accessed November 2018

20 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/history-exam. Last updated April 2017. Accessed 22nd August 2018

21 Treatment of hemophilia (What other treatments are helpful to treat bleeding in hemophiliacs?). Canadian Hemophilia Society. https://www.hemophilia.ca/treatment-of-hemophilia/. Accessed 22nd August 2018

22  Hemophilia A (Overview: management). Medscape. https://emedicine.medscape.com/article/779322-overview. Last updated December 2017 Accessed 22nd August 2018

23 Desmopressin (Mild to moderate haemophilia and von Willebrand's disease). BNF. https://bnf.nice.org.uk/drug/desmopressin.html. Accessed 22nd August 2018

24 Hemophilia B (Overview: management). Medscape. https://emedicine.medscape.com/article/779434-overview. Last updated June 2017. Accessed 22nd August 2018

25 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.6 Prophylactic factor replacement therapy). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

26 Haemophilia (Management: Approach). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/management-approach. Last updated April 2017. Accessed 22nd August 2018

27 Mahlangu J, Powell JS, Ragni MV et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood, 2014, vol 123, issue 3, pp317-25. http://www.bloodjournal.org/content/bloodjournal/early/2013/11/13/blood-2013-10-529974.full.pdf

28 Santagostino E, Martinowitx U, Lissitchkov T et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. BLOOD, April 2016, 127 (14), pp1761-9. In.

http://www.bloodjournal.org/content/bloodjournal/early/2016/01/11/blood-2015-09-669234.full.pdf. Accessed 22nd August 2018

29 Clinical Commissioning Policy: Emicizumab as prophylaxis in people with congenital haemophilia A with factor VIII inhibitors (all ages) NHS England. https://www.england.nhs.uk/wp-content/uploads/2018/07/1717-emicizumab.pdf. Published July 2018. Accessed 22nd August 2018

30 Powell JS, Pasi KJ, Ragni MV et al. Phase 3 Study of Recombinant Factor IX Fc Fusion Protein in Hemophilia B

NEJM, 2013, 369 (24), pp2313-23. In. https://www.nejm.org/doi/full/10.1056/nejmoa1305074. Accessed 22nd August 2018

31 Shima M, Hanabusa H, Taki M, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors (Discussion). Blood Advances. 2017 1:1891-1899; http://www.bloodadvances.org/content/1/22/1891?sso-checked=true#sec-12. Accessed 22nd August 2018

32 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.7 Home therapy). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

33 Oxford Handbook of Clinical Pharmacy (3 ed.)  (Therapy-related issues: cardiovascular system: Understanding anticoagulation: Coagulation factors). Oxford Medicine Online. http://oxfordmedicine.com/view/10.1093/med/9780198735823.001.0001/med-9780198735823-chapter-16?rskey=6N7NwM&result=5. Published online April 2017. Accessed 22nd August 2018

34 Current Issues in Prophylaxis. World Federation of Hemophilia. https://www.wfh.org/en/abd/prophylaxis/current-issues-in-prophylaxis. Last updated March 2016. Accessed 22nd August 2018

35 Updates to the Guidelines for the Management of Hemophilia. World Hemophilia Federation. http://www1.wfh.org/publications/files/pdf-1512.pdf. Published April 2013. Accessed 22nd August 2018

36 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.9 Pain management). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

37 Haemophilia (Complications). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/complications. Last updated April 2017. Accessed 22nd August 2018

38 What are inhibitors? World Hemophilia Federation. https://www.wfh.org/en/page.aspx?pid=651. Accessed 22nd August 2018

39 How does immune tolerance induction work? World Hemophilia Federation. https://www.wfh.org/en/page.aspx?pid=647. Last updated December 2014. Accessed 22nd August 2018

40 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: Table 1-3: Approximate frequency of bleeding at different sites). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

41 Hemophilia A (Overview: Background). Medscape. https://emedicine.medscape.com/article/779322-overview#a2. Last updated December 2017. Accessed 22nd August 2018

42 Hemophilia A Treatment and Management (Approach considerations). Medscape. https://emedicine.medscape.com/article/779322-treatment?src=refgatesrc1. Last updated December 2017. In

43 NHS England, 2013/14 NHS STANDARD CONTRACT FOR HAEMOPHILIA (ALL AGES) https://www.england.nhs.uk/wp-content/uploads/2013/06/b05-haemophilia.pdf. Last accessed December 2018

44 Guidelines for the Management of Hemophilia (1.11 Dental care and management). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1472.pdf. Last updated April 2013. Accessed 22nd August 2018

45 Drugs that can cause bleeding. World Hemophilia Federatio. https://www.wfh.org/en/page.aspx?pid=639. Last updated February 2010. Accessed 22nd August 2018

46 Guidelines for the Management of Hemophilia (2.4 Vaccinations). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1472.pdf. Last updated April 2013. Accessed 22nd August 2018

47 Understanding Haemophilia (Medical and dental treatment: Medicines). The Haemophilia Society. http://haemophilia.org.uk/wp-content/uploads/2017/04/Understanding_haemophilia_WEB.pdf. Published February 2017. Accessed 22nd August 2018

48 Careers with a bleeding disorder and the world of work. The Haemophilia Society. http://haemophilia.org.uk/wp-content/uploads/2017/02/careers_info.pdf.pdf. Last updated November 2014. Accessed 22nd August 2018

49 Specialised Services Circular (SSC) 1652 Sept 2016, on advice of NHS England

50 Elocta SmPC. Electronic Medicines Compendium. https://www.medicines.org.uk/emc/product/5100/smpc. Last updated December 2017. Accessed 22nd August 2018

51 Idelvion SmPC. Electronic Medicines Compendium. https://www.medicines.org.uk/emc/product/2146/smpc. Last updated January 2018. Accessed 22nd August 2018

52 Alprolix SmPC. Electronic Medicines Compendium. https://www.medicines.org.uk/emc/product/7277/smpc. Last updated July 2018. Accessed 22nd August 2018

53 Nathwani AC, Davidoff AM, Tuddenham EGD/ Gene Therapy for Hemophilia. Hematology/Oncology Clinics of North America, October 2017, vol 31, issue 5, pp853-68. https://www.sciencedirect.com/science/article/pii/S0889858817301041?via%3Dihub. Accessed 22nd August 2018

54 HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients. Clinical Trials.Gov

https://clinicaltrials.gov/ct2/show/NCT03569891?term=hemophilia+B&rank=15. Last updated July 2018. Accessed 22nd August 2018

55 Long-term Safety and Efficacy Study of SPK-9001 in Individuals with Hemophilia B. Clinical Trials.Gov. https://clinicaltrials.gov/ct2/show/NCT03307980?term=SPK9001&rank=1. Last updated July 2018. Accessed 22nd August 2018

56 Single-Arm Study to Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia Patients (BMN270-301). Clinical Trials.Gov. https://clinicaltrials.gov/ct2/show/NCT03370913. Last updated July 2018. Accessed 22nd August 2018

57 Pasi KJ, Georgiev P, Mant T et al. A subcutaneously administered investigational RNAi therapeutic (Fitusiran, ALN-AT3) targeting antithrombin for treatment of hemophilia:  interim weekly and monthly dosing results in patients with hemophilia A or B. Presentation to American Hematology Society annual meeting, 2015. http://www.alnylam.com/web/assets/ASH-2015_fitusiran_010715.pdf.  Accessed 22nd August 2018

58 A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors. Clinical Trials.gov

https://clinicaltrials.gov/ct2/show/NCT03417245. Last updated June 2018. Accessed 22nd August 2018
59 Korte W. The Potential Close Future of Hemophilia Treatment - Gene Therapy, TFPI Inhibition, Antithrombin Silencing, and Mimicking Factor VIII with an Engineered Antibody. Transfusion Medicine and Hemotherapy, 2018, 45, 2.
https://www.karger.com/Article/FullText/488152. Accessed 22nd August 2018
60 A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients with Inhibitors (explorer™4).
https://clinicaltrials.gov/ct2/show/NCT03196284?term=concizumab&cond=Hemophilia&rank=3 Last updated October 2018. Accessed 22nd August 2018
61 A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients with Severe Haemophilia A Without Inhibitors (explorer™5).
https://clinicaltrials.gov/ct2/show/NCT03196297?term=concizumab&cond=Hemophilia&rank=1 Last updated September 2018. Accessed 22nd August 2018
62 Multiple Escalating Dose Study of BAY1093884 in Adults With Haemophilia A or B With or Without Inhibitors
https://clinicaltrials.gov/ct2/show/NCT03597022?term=anti-TFPI&cond=Hemophilia&rank=1  Last updated October 2018. Accessed 5th November 2018

Please note that the information provided in the above FAQs is accurate as of December 2018.

The patient advocacy campaign called, Could there be more?, is sponsored by pharmaceutical company, Sobi, who is working in collaboration with The Haemophilia Society and the haemophilia community to launch new haemophilia awareness resources for patients.

Logos

FAQs - New Developments in Haemophilia

Yes, you do have a choice. But doctors in the UK have guidelines that they have to follow and in most cases, any treatment you ask for has to come within the guidelines in order for you to have it. The guidelines are produced by NHS England. Prescribing in Wales and Northern Ireland generally follows the same guidelines. Scotland have their own guideline process but it’s unusual for them to differ very much from the NHS England guidelines.

The way these ‘commissioning guidelines’ work is quite complicated. They cover the ‘commissioning’ of treatments within the NHS. In this sense, commissioning really means what the NHS is prepared to pay for.

The guidelines are built around evidence that treatments work, of course. But they also allow for different brands of the same treatments to be made available.  Currently there are three main brands that are provided to around 7 out of 10 patients. (So it makes up 70% of the prescriptions issued for a type of treatment for haemophilia A, for instance.) Other brands make up the rest.

Overall, the guidelines cover 8 out of 10 prescriptions for a given medical condition. So, there is scope for 2 out of every 10 patients to receive treatments that aren’t covered by the commissioning guidelines. Generally, treatments that aren’t within the commissioning guidelines are much more expensive.

Most people with severe haemophilia in the UK are on standard factor VIII or IX replacement, either on prophylaxis or on-demand treatment. Now there are the newer ‘extended half-life’ (EHL) factor VIII and IX available. There is a separate commissioning guideline covering these and it’s very strict. Basically, overall your treatment has to cost the same on EHL as it would on standard factor replacement. The guidelines are built around evidence that treatments work, of course. But they also allow for different brands of the same treatments to be made available.  Currently there are three main brands that are provided to around 7 out of 10 patients. (So it makes up 70% of the prescriptions issued for a type of treatment for haemophilia A, for instance.) Other brands make up the rest.49 In practice, it’s become more difficult to switch to EHL factor because standard factor is cheaper than it used to be.

Treatments for haemophilia have developed a lot in the past few years. The mainstay of current treatment are clotting factors manufactured without blood donation. Now, a variation of these clotting factors, called extended half-life (EHL) factors are available.50,51,52 The half-life is a measure of how long the clotting factor lasts in your blood stream. EHL factors stay in the blood for longer so people with haemophilia can have the treatment they need to prevent bleeds (prophylaxis) less often.27, 24 With haemophilia A, you may be able to cut down from injections three times a week to twice a week.27 With haemophilia B, you may be able to cut down from twice a week to weekly or even fortnightly injections.24

A treatment that is talked about a lot is gene therapy. This is still in research but is potentially exciting because it could provide a permanent treatment for haemophilia.53 In theory, a single treatment could deliver the gene for making the missing factor and mean that people with haemophilia no longer need factor replacement.53 There are clinical trials underway for gene therapy for both haemophilia A and B.54,55,56

Finally, a new approach to haemophilia treatment is in research. Normally, clotting in the body is held in balance by factors that promote blood clotting and factors that prevent it. Haemophilia researchers have been looking into blocking proteins in the body that normally prevent blood clotting, instead of promoting clotting with injections of factor VIII (8) and factor IX (9).  One of these treatments blocks a body protein called anti-thrombin that stops the blood from clotting.57 You have the treatment as an injection under the skin (subcutaneously) once a month. Early research results have shown a drop in bleeding rates and trials are now comparing it to treatment with factor VIII (8) and IX (9).58

Another similar treatment called anti-TFPI is now being tested. TFPIs (tissue factor pathway inhibitors) are proteins that stop the blood clotting and early research has shown that blocking them in people with haemophilia can help the blood to clot.59 Two anti-TFPI treatments in research can be used for either haemophilia A and haemophilia B and are being tested in people with and without inhibitors.60, 61, 62 As with anti-thrombin, you can have them as injections under the skin (subcutaneously). They are being tested in people who normally have prophylaxis and in those who prefer on-demand treatment.61, 62

Timeline

There is a risk of side effects with any drug.

During their development, all new drugs are monitored very closely for any side effects or safety concerns. The earliest phase of testing takes place in laboratories and it is only after a potential treatment is thought to be safe that it is tested in people. The first round of clinical trials is only designed to test safety. To start with a small number of patients are given a very small dose of the test drug. The dose is gradually increased as more patients join the trial, with all participants being very closely monitored for any problems. This monitoring continues right through the clinical trial process until a treatment is licensed and made available. Even after a drug is put on the market, any reaction or symptom a patient has that could possibly be drug related has to be recorded and reported.

Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.1 What is haemophilia?). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

2 National Organization for Rare Disorders. Hemophilia A. https://rarediseases.org/rare-diseases/hemophilia-a/. Accessed 22nd August 2018

3 National Organization for Rare Disorders. Hemophilia B. https://rarediseases.org/rare-diseases/hemophilia-b/. Accessed 22nd August 2018

4 UK National Haemophilia Database. UK Bleeding Disorder Statistics for April 2016 to March 2017. http://www.ukhcdo.org/wp-content/uploads/2018/02/Bleeding-Disorder-Statistics-for-April-2016-to-March-2017-for-UKHCDO.pdf. Accessed 5th November 2018

5 World Federation of Hemophilia. How do you get haemophilia? https://www.wfh.org/en/page.aspx?pid=644. Accessed 22nd August 2018

6 World Federation of Hemophilia. Carriers and women with haemophilia. https://www.wfh.org/en/abd/carriers/carriers-and-women-with-hemophilia-en. Accessed 22nd August 2018

7 World Federation of Hemophilia. Inheritance of haemophilia. https://www.wfh.org/en/abd/carriers/carriers-inheritance-of-hemophilia-en. Accessed 5th November 2018

8 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/aetiology. Last updated April 2017. Accessed 22nd August 2018

9 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/diagnosis-approach. Last updated April 2017. Accessed 22nd August 2018

10 World Federation of Hemophilia. Carriers and women with haemophilia. https://www.wfh.org/en/abd/carriers/carriers-and-women-with-hemophilia-en. Accessed 22nd August 2018

11 NHS. Causes Haemophlia. https://www.nhs.uk/conditions/haemophilia/causes/. Accessed 22nd August 2018

12 NHS. Symptoms Haemophilia. https://www.nhs.uk/conditions/haemophilia/symptoms/. Accessed 22nd August 2018

13 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.4 Fitness and physical activity). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

14 The Haemophilia Society. What to expect from your treatment centre. http://haemophilia.org.uk/bleeding-disorders/treatment-centres/expectations-treatment-centre/. Accessed 22nd August 2018

15 Haemnet. Haemophilia Nursing. https://www.haemnet.com/external/care/haemophilia-nursing. Accessed 22nd August 2018

16 Haemnet. Haemophilia Physiotherapy. https://www.haemnet.com/external/care/haemphilia-physiotherapy. Accessed 22nd August 2018

17 NHS. Treatment. https://www.nhs.uk/conditions/haemophilia/treatment/ Last updated April 2017. Accessed 22nd August 2018

18 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/prevention. Last updated April 2017. Accessed 22nd August 2018

19 Valentino LA1, Ewenstein B, Navickis RJ, Wilkes MM. Haemophilia. Central venous access devices in haemophilia. 2004 Mar;10(2):134-46. https://www.ncbi.nlm.nih.gov/pubmed/14962202 . Accessed November 2018

20 Haemophilia. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/history-exam. Last updated April 2017. Accessed 22nd August 2018

21 Treatment of hemophilia (What other treatments are helpful to treat bleeding in hemophiliacs?). Canadian Hemophilia Society. https://www.hemophilia.ca/treatment-of-hemophilia/. Accessed 22nd August 2018

22  Hemophilia A (Overview: management). Medscape. https://emedicine.medscape.com/article/779322-overview. Last updated December 2017 Accessed 22nd August 2018

23 Desmopressin (Mild to moderate haemophilia and von Willebrand's disease). BNF. https://bnf.nice.org.uk/drug/desmopressin.html. Accessed 22nd August 2018

24 Hemophilia B (Overview: management). Medscape. https://emedicine.medscape.com/article/779434-overview. Last updated June 2017. Accessed 22nd August 2018

25 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.6 Prophylactic factor replacement therapy). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

26 Haemophilia (Management: Approach). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/management-approach. Last updated April 2017. Accessed 22nd August 2018

27 Mahlangu J, Powell JS, Ragni MV et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood, 2014, vol 123, issue 3, pp317-25. http://www.bloodjournal.org/content/bloodjournal/early/2013/11/13/blood-2013-10-529974.full.pdf

28 Santagostino E, Martinowitx U, Lissitchkov T et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. BLOOD, April 2016, 127 (14), pp1761-9. In.

http://www.bloodjournal.org/content/bloodjournal/early/2016/01/11/blood-2015-09-669234.full.pdf. Accessed 22nd August 2018

29 Clinical Commissioning Policy: Emicizumab as prophylaxis in people with congenital haemophilia A with factor VIII inhibitors (all ages) NHS England. https://www.england.nhs.uk/wp-content/uploads/2018/07/1717-emicizumab.pdf. Published July 2018. Accessed 22nd August 2018

30 Powell JS, Pasi KJ, Ragni MV et al. Phase 3 Study of Recombinant Factor IX Fc Fusion Protein in Hemophilia B

NEJM, 2013, 369 (24), pp2313-23. In. https://www.nejm.org/doi/full/10.1056/nejmoa1305074. Accessed 22nd August 2018

31 Shima M, Hanabusa H, Taki M, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors (Discussion). Blood Advances. 2017 1:1891-1899; http://www.bloodadvances.org/content/1/22/1891?sso-checked=true#sec-12. Accessed 22nd August 2018

32 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.7 Home therapy). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

33 Oxford Handbook of Clinical Pharmacy (3 ed.)  (Therapy-related issues: cardiovascular system: Understanding anticoagulation: Coagulation factors). Oxford Medicine Online. http://oxfordmedicine.com/view/10.1093/med/9780198735823.001.0001/med-9780198735823-chapter-16?rskey=6N7NwM&result=5. Published online April 2017. Accessed 22nd August 2018

34 Current Issues in Prophylaxis. World Federation of Hemophilia. https://www.wfh.org/en/abd/prophylaxis/current-issues-in-prophylaxis. Last updated March 2016. Accessed 22nd August 2018

35 Updates to the Guidelines for the Management of Hemophilia. World Hemophilia Federation. http://www1.wfh.org/publications/files/pdf-1512.pdf. Published April 2013. Accessed 22nd August 2018

36 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: 1.9 Pain management). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

37 Haemophilia (Complications). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/468/complications. Last updated April 2017. Accessed 22nd August 2018

38 What are inhibitors? World Hemophilia Federation. https://www.wfh.org/en/page.aspx?pid=651. Accessed 22nd August 2018

39 How does immune tolerance induction work? World Hemophilia Federation. https://www.wfh.org/en/page.aspx?pid=647. Last updated December 2014. Accessed 22nd August 2018

40 Guidelines for the Management of Hemophilia (General Care and Management of Hemophilia: Table 1-3: Approximate frequency of bleeding at different sites). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1494.pdf. Last updated April 2013. Accessed 22nd August 2018

41 Hemophilia A (Overview: Background). Medscape. https://emedicine.medscape.com/article/779322-overview#a2. Last updated December 2017. Accessed 22nd August 2018

42 Hemophilia A Treatment and Management (Approach considerations). Medscape. https://emedicine.medscape.com/article/779322-treatment?src=refgatesrc1. Last updated December 2017. In

43 NHS England, 2013/14 NHS STANDARD CONTRACT FOR HAEMOPHILIA (ALL AGES) https://www.england.nhs.uk/wp-content/uploads/2013/06/b05-haemophilia.pdf. Last accessed December 2018

44 Guidelines for the Management of Hemophilia (1.11 Dental care and management). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1472.pdf. Last updated April 2013. Accessed 22nd August 2018

45 Drugs that can cause bleeding. World Hemophilia Federatio. https://www.wfh.org/en/page.aspx?pid=639. Last updated February 2010. Accessed 22nd August 2018

46 Guidelines for the Management of Hemophilia (2.4 Vaccinations). World Federation of Hemophilia. http://www1.wfh.org/publications/files/pdf-1472.pdf. Last updated April 2013. Accessed 22nd August 2018

47 Understanding Haemophilia (Medical and dental treatment: Medicines). The Haemophilia Society. http://haemophilia.org.uk/wp-content/uploads/2017/04/Understanding_haemophilia_WEB.pdf. Published February 2017. Accessed 22nd August 2018

48 Careers with a bleeding disorder and the world of work. The Haemophilia Society. http://haemophilia.org.uk/wp-content/uploads/2017/02/careers_info.pdf.pdf. Last updated November 2014. Accessed 22nd August 2018

49 Specialised Services Circular (SSC) 1652 Sept 2016, on advice of NHS England

50 Elocta SmPC. Electronic Medicines Compendium. https://www.medicines.org.uk/emc/product/5100/smpc. Last updated December 2017. Accessed 22nd August 2018

51 Idelvion SmPC. Electronic Medicines Compendium. https://www.medicines.org.uk/emc/product/2146/smpc. Last updated January 2018. Accessed 22nd August 2018

52 Alprolix SmPC. Electronic Medicines Compendium. https://www.medicines.org.uk/emc/product/7277/smpc. Last updated July 2018. Accessed 22nd August 2018

53 Nathwani AC, Davidoff AM, Tuddenham EGD/ Gene Therapy for Hemophilia. Hematology/Oncology Clinics of North America, October 2017, vol 31, issue 5, pp853-68. https://www.sciencedirect.com/science/article/pii/S0889858817301041?via%3Dihub. Accessed 22nd August 2018

54 HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients. Clinical Trials.Gov

https://clinicaltrials.gov/ct2/show/NCT03569891?term=hemophilia+B&rank=15. Last updated July 2018. Accessed 22nd August 2018

55 Long-term Safety and Efficacy Study of SPK-9001 in Individuals with Hemophilia B. Clinical Trials.Gov. https://clinicaltrials.gov/ct2/show/NCT03307980?term=SPK9001&rank=1. Last updated July 2018. Accessed 22nd August 2018

56 Single-Arm Study to Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia Patients (BMN270-301). Clinical Trials.Gov. https://clinicaltrials.gov/ct2/show/NCT03370913. Last updated July 2018. Accessed 22nd August 2018

57 Pasi KJ, Georgiev P, Mant T et al. A subcutaneously administered investigational RNAi therapeutic (Fitusiran, ALN-AT3) targeting antithrombin for treatment of hemophilia:  interim weekly and monthly dosing results in patients with hemophilia A or B. Presentation to American Hematology Society annual meeting, 2015. http://www.alnylam.com/web/assets/ASH-2015_fitusiran_010715.pdf.  Accessed 22nd August 2018

58 A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors. Clinical Trials.gov

https://clinicaltrials.gov/ct2/show/NCT03417245. Last updated June 2018. Accessed 22nd August 2018
59 Korte W. The Potential Close Future of Hemophilia Treatment - Gene Therapy, TFPI Inhibition, Antithrombin Silencing, and Mimicking Factor VIII with an Engineered Antibody. Transfusion Medicine and Hemotherapy, 2018, 45, 2.
https://www.karger.com/Article/FullText/488152. Accessed 22nd August 2018
60 A Trial Evaluating the Efficacy and Safety of Prophylactic Administration of Concizumab in Haemophilia A and B Patients with Inhibitors (explorer™4).
https://clinicaltrials.gov/ct2/show/NCT03196284?term=concizumab&cond=Hemophilia&rank=3 Last updated October 2018. Accessed 22nd August 2018
61 A Trial Evaluating Efficacy and Safety of Prophylactic Administration of Concizumab in Patients with Severe Haemophilia A Without Inhibitors (explorer™5).
https://clinicaltrials.gov/ct2/show/NCT03196297?term=concizumab&cond=Hemophilia&rank=1 Last updated September 2018. Accessed 22nd August 2018
62 Multiple Escalating Dose Study of BAY1093884 in Adults With Haemophilia A or B With or Without Inhibitors
https://clinicaltrials.gov/ct2/show/NCT03597022?term=anti-TFPI&cond=Hemophilia&rank=1  Last updated October 2018. Accessed 5th November 2018

Please note that the information provided in the above FAQs is accurate as of December 2018.

The patient advocacy campaign called, Could there be more?, is sponsored by pharmaceutical company, Sobi, who is working in collaboration with The Haemophilia Society and the haemophilia community to launch new haemophilia awareness resources for patients.

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