98% of patients maintained or extended dosing intervals with ELOCTATE®

Change in Infusion Interval From the End of Kids A-LONG to ASPIRE Interim Data Cut6

98% of patients maintained or extended dosing intervals with ELOCTATE during ASPIRE.

Full study designs

  • ELOCTATE recommended starting regimen: 50 IU/kg administered every 4 days. For children <6 years of age, 50 IU/kg administered twice weekly1
  • Adjust the regimen based on patient response with dosing in the range of 25 to 65 IU/kg at 3- to 5-day intervals. In children <6 years of age, more frequent or higher doses up to 80 IU/kg may be required1

As children grow older with ELOCTATE®, they may extend dosing up to every 5 days

Mean Terminal Half-life in the Pediatric Population After Single Dose (50 IU/kg)1

chart2
  • A comparison of pharmacokinetic parameters by age shows an extended half-life correlating with a consistent decrease in body weight–adjusted clearance

Pharmacokinetic (PK) parameters in adult patients1

Parameters*Kids A-LONG1A-LONG1
1–5 years of age (N=23)6–11 years of age (N=31)12–17 years (N=11)
IR (IU/dL per IU/kg)1.92 (1.80, 2.04)2.44 (2.07, 2.80)1.85 (1.58, 2.12)
AUC/Dose (IU x h/dL per IU/kg)30.0 (26.5, 33.6)41.9 (34.0, 49.8)38.7 (34.3, 43.1)
t1/2 (h)12.7 (11.2, 14.1)14.9 (12.0, 17.8)16.4 (14.1, 18.6)
MRT (h)17.2 (15.4, 19.1)20.9 (17.1, 24.7)23.1 (19.9, 26.4)
CL (mL/h/kg)3.60 (3.13, 4.07)2.78 (2.44, 3.13)2.66 (2.34, 2.98)
VSS (mL/kg)58.6 (54.9, 62.3)52.1 (45.3, 59.0)60.3 (53.3, 67.3)

* PK parameters are presented in arithmetic mean (95% CI).

AUC=area under the curve; CL=clearance; IR=incremental recovery; MRT=mean residence time;
t1/2=terminal half-life; VSS=body weight–adjusted volume of distribution at steady state.

ELOCTATE® uses a naturally occurring pathway and does not accumulate in the body1,11

  • ELOCTATE is the first factor VIII with an extended half-life, expressed in a human cell line using recombinant DNA technology1,7
  • The B-domain–deleted recombinant fusion protein (BDD-rFVIIIFc) consists of human coagulation factor VIII covalently linked to the Fc domain of human IgG11
ELOCTATE binds to the neonatal Fc receptor (FcRn), which naturally diverts ELOCTATE, temporarily delaying the degradation of immunoglobulins and extending half-life

ELOCTATE binds to the neonatal Fc receptor (FcRn), which naturally diverts ELOCTATE, temporarily delaying the degradation of immunoglobulins and extending half-life1,11

ELOCTATE works with IgG1. The precise mechanism that prolongs the half-life of ELOCTATE has not been fully defined; however, preclinical animal studies suggest the above.

ELOCTATE works with IgG1, a naturally occurring protein that has anti-inflammatory and other properties1,12

The precise mechanism that prolongs the half-life of ELOCTATE has not been fully defined; however, preclinical animal studies suggest the above.

Calculate your patient's ELOCTATE® starting dose for routine prophylaxis, bleed control, or surgery1

Starting prophylactic dose

00

2x weekly

80

75

70

65

60

55

50

45

40

35

30

25

Adjust the regimen based on patient response with dosing in the range of 25 to 65 IU/kg at 3- to 5-day intervals. In children <6 years of age, more frequent or higher doses up to 80 IU/kg may be required.

Minor to moderate*
bleed control

00

30

25

20

Major
bleed control

00

50

45

40

Estimated increment of factor VIII (% of normal)

50%

100%

Factor VIII level required (IU/dL or % of normal)

40–60

80–100

Dose range (IU/kg)

20–30

40–50

Frequency of dosing (hours)

Repeat every 24–48 hours (12–24 hours for patients <6 years of age)

Repeat every 12–24 hours (8–24 hours for patients <6 years of age)

Duration of therapy (days)

Until the bleeding episode is resolved

Until the bleeding episode is resolved (approximately 7–10 days)

Information in the above calculator is provided as a guide for dosing ELOCTATE for the control of bleeding episodes. Your independent medical consideration should be given to maintaining factor VIII activity at or above the target range.

*Minor and moderate bleed events: joint, superficial muscle/no neurovascular compromise (except iliopsoas), deep laceration and renal, superficial soft tissue, mucous membranes.

Major bleed events: life- or limb-threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, retroperitoneum, intracranial, or gastrointestinal.

x 25–40 IU/kg =

Preoperative dose

00

00

*Minor surgery example: uncomplicated tooth extraction.

Major surgery example: intracranial, intra-abdominal, or joint replacement.

Factor VIII level required (IU/dL or % of normal)

50–80

Dose range (IU/kg)

25–40

Frequency of dosing (hours)

Repeat every 24 hours (12–24 hours for patients <6 years of age)

Duration of therapy (days)

At least 1 day until healing is achieved

Information in the above calculator is provided as a guide for dosing ELOCTATE during surgery (perioperative management). Your independent medical consideration should be given to maintaining factor VIII activity at or above the target range.

Preoperative

00

60

55

50

45

40

Repeat

00

50

45

40

*Minor surgery example: uncomplicated tooth extraction.

Major surgery example: intracranial, intra-abdominal, or joint replacement.

Factor VIII level required (IU/dL or % of normal)

80–120

Frequency of dosing (hours)

Preoperative dose of 40–60 IU/kg followed by a repeat dose of 40–50 IU/kg after 8–24 hours (6–24 for patients <6 years of age) and then every 24 hours to maintain FVIII activity within the target range

Duration of therapy (days)

Until adequate wound healing, then continue therapy for at least 7 days to maintain a factor VIII activity within the target range

Information in the above calculator is provided as a guide for dosing ELOCTATE during surgery (perioperative management). Your independent medical consideration should be given to maintaining factor VIII activity at or above the target range.

Type of Surgery5Number of Procedures (Number of Patients)Hemostatic Response
ExcellentGood
Major surgery23* (22)193
Arthrodesis1 (1)1
Ankle fusion2 (2)2
Appendectomy1 (1)1
Arthroscopy2 (2)2
Ventriculostomy1 (1)1
Laparoscopic hernia surgery2 (2)11
Discopathy repair1 (1)1
Decompression of spine stenosis1 (1)1
Arthroplasty11 (10)91
Knee arthroplasty converted to amputation1 (1)1

*Across A-LONG and ASPIRE, 22 patients underwent 24 major surgeries. One surgery was not evaluable because the patient received a nonstudy drug.

Results based on a 4-point scale of excellent, good, fair, and poor/none. The median dose per infusion was 58.3 IU/kg (range, 45–102 IU/kg). The total dose on the day of surgery ranged from 50.8 to 126.6 IU/kg.

One surgical rating was not available.

Graphic is for illustrative purposes only.

Eligibility criteria apply. Those with federal and state government insurance, such as Medicare, Medicaid, or TRICARE®, are not eligible. Have your patients contact their MyELOCTATE™ Coordinator to see if they are eligible for any of these programs. Bioverativ® reserves the right to change these programs at any time. TRICARE is a registered trademark of the Department of Defense (DoD), DHA. All rights reserved.

Important Safety Information

CONTRAINDICATIONS: ELOCTATE is contraindicated in patients who have had life-threatening hypersensitivity reactions to ELOCTATE or its excipients.

WARNINGS AND PRECAUTIONS: Hypersensitivity reactions have been reported with ELOCTATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with Factor VIII replacement products. Immediately discontinue ELOCTATE and initiate appropriate treatment if hypersensitivity reactions occur. Formation of neutralizing antibodies (inhibitors) to Factor VIII has been reported following administration of ELOCTATE, including in previously untreated patients. Patients using ELOCTATE should be monitored for the development of Factor VIII inhibitors. Clotting assays (e.g., one-stage) may be used to confirm that adequate Factor VIII levels have been achieved and maintained.

ADVERSE REACTIONS: The most frequently occurring adverse reactions (>0.5% of subjects) in clinical trials were arthralgia, malaise, myalgia, headache, and rash.

INDICATIONS

ELOCTATE® [Antihemophilic factor (recombinant), Fc fusion protein] is a recombinant DNA derived, antihemophilic factor indicated in adults and children with Hemophilia A (congenital Factor VIII deficiency) for: on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.

Limitation of Use
ELOCTATE is not indicated for the treatment of von Willebrand disease.

References: 1. ELOCTATE® [package insert]. Waltham, MA: Bioverativ®; 2017. 2. Nolan B, et al. Haemophilia. 2016;22:72-80. 3. Data on file, Bioverativ®, a Sanofi Company. 4. Blanchette VS, et al. J Thromb Haemost. 2014;12(11):1935-1939. 5. Mahlangu JN, et al. Thromb Haemost. 2016;116:1-8. 6. Nolan B, et al. Haemophilia. 2016;22(1)(suppl):1-10. 7. Mahlangu J, et al. Blood. 2014;123(3):317-325. 8. Clinicaltrials.gov. NCT01454739. https://clinicaltrials.gov/ct2/show/NCT01454739. Accessed April 25, 2018. 9. Young G, et al. J Thromb Haemost. 2015;13:1-11. 10. Clinicaltrials.gov. NCT02234323. https://clinicaltrials.gov/ct2/show/NCT02234323. Accessed April 25, 2018. 11. Shapiro A. Expert Opin Biol Ther. 2013;13(9):1287-1297. 12. Kaneko Y, et al. Science. 2006;313:670-673. 13. ADVATE® [package insert]. Westlake Village, CA: Baxalta US Inc.; 2016. 14. ADYNOVATE® [package insert]. Westlake Village, CA: Baxalta US Inc.; 2016. 15. AFSTYLA® [package insert]. Kankakee, IL: CSL Behring LLC; 2017. 16. ALPHANATE® [package insert]. Los Angeles, CA: Grifols Biologicals Inc.; 2015. 17. HEMOFIL M® [package insert]. Westlake Village, CA: Baxalta US Inc.; 2016. 18. HUMATE-P® [package insert]. Kankakee, IL: CSL Behring LLC; 2014. 19. KOATE®-DVI [package insert]. Research Triangle Park, NC: Grifols Therapeutics Inc.; 2012. 20. KOGENATE FS® [package insert]. Whippany, NJ: Bayer HealthCare LLC; 2016. 21. KOVALTRY® [package insert]. Whippany, NJ: Bayer HealthCare LLC; 2016. 22. MONOCLATE-P® [package insert]. Kankakee, IL: CSL Behring LLC; 2014. 23. NOVOEIGHT® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; 2016. 24. NUWIQ® [package insert]. Hoboken, NJ: Octapharma USA, Inc.; 2015. 25. RECOMBINATE® [package insert]. Westlake Village, CA: Baxalta US Inc.; 2017. 26. REFACTO® [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2007. 27. XYNTHA® [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2014. 28. Lara M, Duncan N, Andres R. Effect of hemophilia treatment center digital monitoring on bleeding rates: 12 month study. Am J Hematol. 2016;91(9):E408.