ELOCTATE® prophylaxis demonstrated a median ABR <1 over 4 years

A-LONG1* Pivotal Study

  • On-demand treatment (n=23)
  • Individualized prophylaxis (n=117)

*A-LONG was an open-label, multicenter study that investigated the safety, efficacy, and pharmacokinetics (PK) of ELOCTATE for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in previously treated males ≥12 years of age with severe hemophilia A.Of 117 patients enrolled in the individualized prophylaxis arm, 112 were treated for ≥6 months. Dosing intervals were evaluated during the last 3 months of the study. Number of infusions may vary per individual. Individualized prophylaxis regimen: 25 IU/kg and 50 IU/kg of ELOCTATE on the first and fourth days of the week, respectively. Dose adjustments (25 to 65 IU/kg) and interval (every 3 days) were allowed based on a patient’s PK data and observed bleeding pattern.1

ASPIRE2† Extension Study

  • On-demand treatment (n=14)
  • Modified prophylaxis (n=17)
  • Individualized prophylaxis (n=108)

ASPIRE was an open-label, multicenter, nonrandomized evaluation of ELOCTATE that included a subset of 150 previously treated males ≥12 years of age with hemophilia A who completed the A-LONG pivotal trial.ASPIRE was an extension study that demonstrated the long-term efficacy and safety of ELOCTATE prophylaxis regimens and on-demand treatment, as well as perioperative hemostatic efficacy in patients undergoing surgical procedures. The primary endpoint was development of inhibitors (neutralizing antibodies). Key secondary endpoints included ABR, exposure days, and patient's assessment of response to treatment of a bleeding episode. Interim data were cut January 6, 2014. At the interim data cut, the median time on ASPIRE among patients from A-LONG was 80.9 weeks. The individualized prophylaxis regimen was 25 to 65 IU/kg every 3 to 5 days or twice weekly (20 to 65 IU/kg on Day 1, 40 to 65 IU/kg on Day 4).2

Full study designs

ABR=annualized bleed rate.

Median ABR remained <1 even in patients with 1 target joint

ASPIRE3 2011–2016
(Data Cut 3)

Data from the third interim cut of ASPIRE taken on January 11, 2016. In patients on ELOCTATE prophylaxis for at least 12 months who had target joints at baseline, 234 out of 235 target joints were resolved. Forty-eight patients had no target joint bleeding episodes.3

Full study designs

*A target joint is defined as a major joint with ≥3 bleeding episodes in a consecutive 6-month period. Target joint resolution is defined as ≤2 spontaneous bleeds in a 12-month period.4

ABR=annualized bleed rate; EHL=extended half-life; rFVIII=recombinant factor VIII.

Over 4 years, nearly all bleeds were controlled with 2 infusions of ELOCTATE®

Full study designs

*The total number of bleeding episodes was 828 for ASPIRE for all treatment arms, including 262 bleeds for 11 patients who were treated on demand.2

In A-LONG, 757 bleeding episodes in 106 patients were treated with ELOCTATE, including 456 bleeds for 23 patients who were treated on demand. One or 2 infusions were required to treat 97.7% of bleeding episodes.1,3

Per the FDA-approved Prescribing Information, 78.1% of patients rated the response to the first infusion of ELOCTATE as “excellent” or “good.” “Excellent” was defined as abrupt pain relief and/or improvement in bleeding; “good” was defined as definite pain relief and/or improvement in signs of bleeding, but possibly requiring more than 1 infusion. Response was evaluated approximately 8 to 12 hours after treatment.

ABR=annualized bleed rate.

ELOCTATE® demonstrated efficacy across a wide range of surgeries

66 total surgeries* in patients 12 years of age5

Major surgeries: 24 total in 22 patients

Most common:

  • Unilateral knee arthroplasty (n=7)
  • Ankle fusion (n=3)

Response:

  • 22 (92%) major surgeries required just 1 infusion to maintain hemostasis during surgery

Minor surgeries: 42 total in 31 patients

Response:

  • For 39 (93%) surgeries in adolescents and adults, the median number of infusions on the day of surgery was 1 (range, 1–2)
  • In 100% of all surgeries assessed, hemostatic response was rated “excellent” or “good”

*From A-LONG and ASPIRE.

Full study designs

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.

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: Sanofi Genzyme, 2017. 2. Nolan B, et al. Haemophilia. 2016;22:72-80. 3. Data on file, Bioverativ Therapeutics Inc., an affiliate of Sanofi. 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.