Median AsjBR With ELOCTATE® Individualized Prophylaxis

Median AsjBR in pediatric patients taking ELOCTATE individualized prophylaxis was 0.0 during Kids A-LONG and remained at 0.0 during ASPIRE.

Over
2 years

ASPIRE2* (N=59)

0.0 median overall ABR for subjects <6 years of age. 1.5 median overall ABR for subjects 6–11 years of age.

*ASPIRE was an open-label, multicenter, nonrandomized evaluation of ELOCTATE in a subset of 61 previously treated males <12 years of age with hemophilia A who completed the Kids A-LONG pivotal trial. 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). 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 Kids A-LONG was 23.9 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). In patients <12 years of age, dose adjustments were made up to a maximum of 80 IU/kg up to every 2 days, if necessary.2

In Kids A-LONG, there were 86 bleeding episodes treated with ELOCTATE in 69 patients.50% of patients in the modified prophylaxis arm (n=2) experienced zero bleeds.1,2

ABR=annualized bleed rate; AsjBR=annualized spontaneous joint bleed rate.

Median ABR remained low even in patients with 1 target joint

ASPIRE2 2013–2014
(Data Cut 2)

Median annualized bleed rate was 4.4 for patients 1 to 5 years of age and 1.8 for patients 6 to 11 years of age taking ELOCTATE individualized prophylaxis.

ASPIRE3 2013–2016
(Data Cut 3)

Data are 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, 9 out of 9 target joints were resolved. Seven subjects 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.

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

Full study designs

*The total number of bleeding episodes was 51 for ASPIRE.2

In Kids A-LONG, 86 bleeding episodes in 69 patients were treated with ELOCTATE, and 93.0% required 1 or 2 infusions to treat a bleeding episode.1

Per the FDA-approved Prescribing Information, 92.6% 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.

ELOCTATE® demonstrated efficacy across a wide range of surgeries

10 total surgeries* in patients 11 years of age5

Major surgeries: 10 total in 10 patients

Response:

  • The median number of infusions on the day of surgery was 2 (range, 1–3)
  • In 100% of all surgeries assessed, hemostatic response was rated “excellent” or “good”

Minor surgeries: No major surgeries were performed after the first dose of ELOCTATE in the Kids A-LONG study

In adults:

Major surgeries: 24 total in 22 patients

Response:

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

*From Kids 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.

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