Esperoct

Haemophilia A
& FVIII Levels

Explore
Esperoct^®

Esperoct^®
Efficacy Profile

Esperoct^® Safety
Profile

Esperoct^® Storage
& Reconstitution

Surgery &
On-demand Use

Paediatric
Patients

About
Haemophilia

Exercise, physical
activity and healthy
eating

FVIII, factor VIII; WFH, World Federation of Hemophilia
*Higher than 3% FVIII activity levels ¹

The image shown is a model and not a real patient
ABR, annualised bleed rate; EHL, extended half life; FVIII , factor VIII; rFVIII , recombinant factor VIII
^*In studies of previously treated patients,12 years and above^2

**Prophylaxis: the recommended dose is 50 IU of Esperoct^® per kg of body weight every 4 days. Adjustments of doses and administration intervals may be considered based on achieved FVIII levels and individual bleeding tendency^2

†3% mean trough levels observed^{2,3,9

††}Total ABR for all bleeds, including spontaneous and traumatic bleeds^3

‡Refer to Esperoct^® SmPC for full storage conditions²

FVIII, factor VIII; PEG, polyethylene glycol; rFVIII, recombinant factor VIII
^*3% mean trough levels observed^2,3,9

^*Results from a post hoc analysis of patients who completed the entire pathfinder 2 trial are shown. In pathfinder 2, a Phase III trial, 186 previously treated patients≥12 years of age with severe haemophilia A were treated with Esperoct^® for a median of 5.4 years. 177 patients received Esperoct^® prophylaxis of 50 IU/kg every 4 days. Bleeding episodes were treated with Esperoct^® doses of 20-75 IU/kg3
^**Number of patients who were on Esperoct^® 50 IU/kg every 4 days prophylaxis was different in each year of the trial^3

†Total ABR for all bleeds, including spontaneous and traumatic bleeds^3

††A general trend for reduction in bleed frequency over time was observed^3,10

71patients switched from Esperoct^® 50 IU/kg every 4 days in pathfinder 2 to 50 IU/kg twice weekly in pathfinder8 ^11

‡‡Results from pathfinder 8, a Phase III trial of patients recruited from the completed pathfinder 2 trial. Patients received Esperoct^® for up to 104 weeks, administered every 7 days, twice weekly or three times weekly . Number of patients who were on Esperoct^® 50 IU/kg twice weekly prophylaxis was different in each year of the trial^11

§Out of 71 patients (who switched from Esperoct® 50 IU/kg every 4 days in pathfinder 2 to 50 IU/kg twice weekly in pathfinder 8),61remained on 50 IU/kg twice weekly dosing in the second year of pathfinder 8^11

§§Of 71 patients, 30 had a mean ABR >1^11

***Compared with patients who had a lower ABR ≤1^{11

†††}Demonstrated in 90% of patients who had a mean ABR >1 while dosing Esperoct^® 50 IU/kg every 4 days in pathfinder 2¹¹

The image shown is a model and not a real patient

Only Esperoct^® offers storage flexibility between 30^° and 40^°C for up to 3 months among EHL rFVIIIs^{2, 5-8}

EHL, extended half life; rFVIII , recombinant factor VIII

FVIII level required (% or IU/dL):
80–100 (pre- and post-operative)

Dose within one hour before surgery to achieve FVIII activity within the target range. Repeat every 8 to 24 hours to maintain FVIII activity within the target range^†

FVIII, factor VIII

^*Successful haemostasis was defined as a rating of ‘excellent’ or ‘good’. Success rate was evaluated on the day of surgery by the investigator using a four point scale category response: ‘Excellent’ (better than expected/predicted for this type of procedure); ‘Good’ (as expected); ‘Moderate’ (less than optimal haemostatic response, but maintained with no change in treatment regimen); ‘None’ (bleeding due to inadequate therapeutic response to adequate dosing; change in regimen required)^13,14
^**Refer to Esperoct® SmPC for full dosing guidance²
^†Repeat injection every 8 to 24 hours as necessary until adequate wound healing is achieved. Consider continuing therapy for another 7 days to maintain FVIII activity of 30-60% (IU/ dL)²

The image shown is a model and not a real patient

65 IU/kg twice weekly, with the possibility of individualising dose and dosing
interval based on achieved FVIII levels and individual bleeding tendency

per year if previously dosed
every other day¹⁵

per year if previously dosed
3 times per week¹⁵

ABR, annualised bleed rate; FVIII, factor VIII; IQR, interquartile range
^*Pathfinder 5, a Phase III, multinational, open label, single arm trial evaluated the safety, efficacy and pharmacokinetics of Esperoct^® in 68 previously treated paediatric (<12 years) patients with severe haemophilia A. For prophylaxis, Esperoct^® was dosed at 50 75 IU/kg twice weekly. Bleeds were treated with Esperoct^® 20 75 IU/kg^16

**Results from a post hoc analysis of paediatric patients who completed the entire pathfinder 5 trial are shown. Number of patients who were on Esperoct^® 60 IU/kg (range: 50 70 IU/kg) twice weekly prophylaxis was different in each year of the trial 12
^†Total ABR for all bleeds, including spontaneous and traumatic bleeds¹⁶
^††A general trend for reduction in bleed frequency over time was observed^10,16
^‡A target joint was defined as a single joint with ≥ 3 bleeding episodes in 6 consecutive months. All baseline target joints reached the per protocol definition of target joint resolution in slightly over 2 years of treatment with Esperoct^®. Per protocol, a target joint was no longer considered a target joint if there were no bleeding episodes for 12 consecutive months. 12 patients, with 16 documented target joints at the baseline, participated in the main and extension phase of pathfinder 5 clinical trial^16

‡‡Compared with standard prophylactic regimen if patient is dosing Esperoct^® twice a week¹⁵

It can also lead to
spontaneous internal
and external bleeding.¹⁷

People with haemophilia are
missing or do not have
enough clotting factor,
a protein in the blood that helps
to control bleeding and clotting.¹⁷

Haemophilia is divided into two different types, A and B

means that factor
levels are less
than 1%.^17,20

means that factor
levels are 1–5%.^17,20

means that factor
levels are 6–30%.^17,20

• The gene for haemophilia is located only on the X chromosome. So, if a son inherits an X chromosome carrying haemophilia from his mother, he will have haemophilia.²⁰

• A father with haemophilia cannot pass it on to his sons but will pass the gene to his daughters.²⁰

• Carriers have around half the normal amount of factor VIII and factor IX and can also suffer symptoms.²⁰

Bruising more
easily

Prolonged bleeding
after surgery

Serious bleeding
after trauma and
longer time to heal

More likely to require an iron
supplement or to undergo
hysterectomy and are more likely
to have bleeding following
childbirth.

Along with the physical
symptoms, there may be a
psychological and mental
health impact from being a
haemophilia carrier.

EASY BRUISING

SPONTANEOUS
BLEEDING
(i.e. bleeding for no
apparent/known reason),
particularly into the joints,
muscles, and soft tissues

EXCESSIVE BLEEDING
FOLLOWING TRAUMA
OR SURGERY

Inhibitors occur when the body has an immune response to treatment with clotting factor concentrates and recombinant factor products, which means “standard” treatment becomes ineffective.

The medical and scientific community is continuing to work towards preventing the development of inhibitors, as well as establishing how best to
manage treatment for those who have already developed inhibitors.

can be used to treat bleeding episodes. Instead of replacing the missing factor, they go around (or bypass) the factors that are blocked by the inhibitors to help the body form a normal clot.³²

are artificial proteins that are designed to mimic the function of the missing factor. They bridge together two different types of factors to help continue the natural clotting mechanism.³²

can directly remove inhibitors from the person's blood, the process can however take quite a long time, from months to years of therapy.³²

Joint protection from further
injury and bleeds as well as
avoiding chronic posture changes

Reduced joint swelling
and pain

Improved joint stability, bone
mineral density, muscle
strength, and range of motion

Reaching and maintaining a
healthy weight to reduce the
stress on joints

Bleeding into the joints (hemarthrosis) and subsequent joint damage (arthropathy) are the most common complications seen in haemophilia.

In some cases, if bleeds continue to occur in a particular joint, this will become what is known as a “target joint”.

Target joints generally occur when there have been three bleeds into the same joint in a six-month time period. The most common target joints are the knees, ankles, and elbows, leading to a limited range of movement and pain.

1. World Federation of Hemophilia (WFH). Guidelines for the management of hemophilia, 3rd edition.
Available at: https://www.wfh.org/en/resources/wfh-treatment-guidelines (Accessed May 2023).

2. Esperoct^® Summary of Prduct Characteristics

3. Gianfrande P et al. J Thromb Haemost 2020; 18:5-14.

4. Chowdary P et al. Res Pract Thromb Haemost 2019; 3:542-554.

5. Napolitano M et al. J Blood Med 2021; 12:9-20.

6. Adynovi^® Summary of Product Characteristics.

7. Elocta^® Summary of Product Characteristics.

8. Jivi^® Summary of Product Characteristics.

9. Giangrande P et al. J Thromb Haemost 2017; 117:252-261.

10. Tiede A et al. Haemophilia 2022; 28:27-3.

11. Lentz S et al. Res Pract Thromb Haemost 2022; 6:1-12.

12. Munn J et al. J Haem Practice 2016; 3:33-38.

13. Tosetto A et al. Haemophilia 2020; 26:450-458.

14. Tosetto A et al. Haemophilia 2020; 26 suppl:1-12.

15. Esperoct^® Patient Information Leaflet.

16. Trakymiene SŠ et al. J Thromb Haemost 2020; 6:15-20.

17. Peyvandi F, et al. J Thromb Haemost. 2016;14:2095-2106.

18. Haemophilia. The Haemophilia Society. 2023. (Available at: https://haemophilia.org.uk/bleedingdisorders/haemophilia-a-and-b/. Last access: May 2023).

19. Types of Haemophila. The Haemophilia Society.2023 (Available at: https://haemophilia.org.uk/bleeding-disorders/haemophilia-a-and-b/types-of-haemophilia/. Last access: May 2023).

20. National Haemophilia Foundation. Bleeading Disorder. Haemophilia A. 2023 (Available at: https://www.hemophilia.org/bleeding-disorders-a-z/types/hemophilia-a. Last access: May 2023).

21. Hirayama AB, et al. Hematol Transfus Cell Ther. 2019;41:349-355.

22. MedlinePlus 2020 National Institutes of Health. Hemophilia. Available from https://medlineplus.gov/genetics/condition/hemophilia/. Last Accessed May 2023.

23. Paroskie A, et al. Br J Haematol. 2015;170:223-228.

24. World Federation of Hemophilia, eLearning Centres, Carrier and Women with Hemophilia, 2020.
Available from https://elearning.wfh.org/elearning-centres/carriers-and-women-with-hemophilia/#carriers_bleeding_symptoms Last Accessed May 2023.

25. Srivasta A et al, Haemophilia. 2020;26 Suppl 6:1-158

26. Centres of Disease Control and Prevention, Diagnosis of Hemophilia. (Available at: https://www.cdc.gov/ncbddd/hemophilia/diagnosis.html. Last access: May 2023).

27. KULKARNI.R.et al. Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System. Haemophilia. 2017 March ;23(2): 207–214.

28. World Federation of Hemophilia. HEMOPHILIA. (Available at: https://elearning.wfh.org/elearningcentres/hemophilia/?_ga=2.41069547.894181855. Last access: May 2023).

29. Alabek M, Mohan R and Raia MH. Genetic Counselling for Hemophilia. World Federation of Hemophilia, July 2015, No 25.

30. Carcao M and Goudemand J, Inhibitors in Hemophilia: A primer, World Federation of Hemophilia November 2018. No 7.

31. World Federation of Hemophilia, eLearning Centres, What are Inhibitors. 2023 (Available at: https://elearning.wfh.org/elearning-centres/inhibitors/?_ga=2.168554472.894181855.1683534767-844884120.Last access: May 2023).

32. Centres of Disease Control and Prevention, Inhibitors and Hemophilia. 2020.

33. Oldenburg J, et al. N Engl J Medicine, 2017,377;9:809-818.

34. National Hemophilia foundation, Immune Tolerance 2023. (Available at: https://www.hemophilia.org/bleeding-disorders-a-z/overview/inhibitors/immune-tolerance. Last access: May 2023).

35. MULDER,K. and LLINA´S,A. et al. The target joint. Haemophilia (2004), 10, (Suppl. 4), 152–156.

36. Biasoli,C. et al. Promoting physical activity in people with haemophilia: the MEMO (Movement for persons with haEMOphilia) expert consensus project. Blood Transfus 2022; 20: 66-77persons with haEMOphilia) expert consensus project. Blood Transfus 2022; 20: 66-77

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