ASH Clinical News November 2015 | Page 46

Literature Scan
“Early discharge following intensive AML
or MDS chemotherapy can reduce costs
and use of IV antibiotics, but attention
should be paid to complications that
may occur in the outpatient setting.”
—JENNIFER E. VAUGHN, MD

ELOCTATE™ [Antihemophilic Factor (Recombinant), Fc Fusion Protein]
Lyophilized Powder for Solution For Intravenous Injection.

Table 3: Adverse Reactions Reported for ELOCTATE (N=164)
MedDRA System Organ Class

MedDRA Preferred Term

Brief Summary of Full Prescribing Information.

1 INDICATIONS AND USAGE

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:
• Control and prevention of bleeding episodes,
• Perioperative management (surgical prophylaxis),
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
ELOCTATE is not indicated for the treatment of von Willebrand disease.

4 CONTRAINDICATIONS

ELOCTATE is contraindicated in patients who have had life-threatening hypersensitivity
reactions to ELOCTATE, including anaphylaxis.
5.1 Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, are possible with ELOCTATE. Early signs
of hypersensitivity reactions that can progress to anaphylaxis may include angioedema,
chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue
administration and initiate appropriate treatment if hypersensitivity reactions occur.
5.2 Neutralizing Antibodies
Formation of neutralizing antibodies (inhibitors) to Factor VIII can occur following
administration of ELOCTATE. Monitor all patients for the development of Factor VIII
inhibitors by appropriate clinical observations and laboratory tests. If the plasma
Factor VIII level fails to increase as expected or if bleeding is not controlled after
ELOCTATE administration, suspect the presence of an inhibitor (neutralizing antibody).
[see Monitoring Laboratory Tests (5.3)]
5.3 Monitoring Laboratory Tests
• Monitor plasma Factor VIII activity by performing a validated test (e.g., one stage
clotting assay), to confirm that adequate Factor VIII levels have been achieved and
maintained. [see Dosage and Administration (2)]
• Monitor for the development of Factor VIII inhibitors. Perform a Bethesda inhibitor
assay if expected Factor VIII plasma levels are not attained, or if bleeding is not
controlled with the expected dose of ELOCTATE. Use Bethesda Units (BU) to report
inhibitor levels.

6 ADVERSE REACTIONS

Common adverse reactions (≥1% of subjects) reported in clinical trials were arthralgia
and malaise.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of one drug cannot be directly compared to rates in
clinical trials of another drug and may not reflect the rates observed in practice.
In the multi-center, prospective, open-label, clinical trial of ELOCTATE, 164 adolescent
and adult, previously treated patients (PTPs, exposed to a Factor VIII containing product
for ≥150 exposure days) with severe Hemophilia A (<1% endogenous FVIII activity or
a genetic mutation consistent with severe Hemophilia A) received at least one dose
of ELOCTATE as part of either routine prophylaxis, on-demand treatment of bleeding
episodes or perioperative management. A total of 146 (89%) subjects were treated for at
least 26 weeks and 23 (14%) subjects were treated for at least 39 weeks.
Adverse reactions (ARs) (summarized in Table 3) were reported for nine (5.5%) subjects
treated with routine prophylaxis or episodic (on-demand) therapy.
Two subjects were withdrawn from study due to adverse reactions of rash and arthralgia.
In the study, no inhibitors were detected and no events of anaphylaxis were reported.
Table 3: Adverse Reactions Reported for ELOCTATE (N=164)
MedDRA Preferred Term

Vascular disorders

Angiopathy*
Hypertension

Cardiac disorders

Bradycardia

1 (0.6)

Injury, poisoning, and
procedural complications

Procedural hypotension

1 (0.6)

Respiratory, thoracic,
and mediastinal disorders

Cough

1 (0.6)

Skin and subcutaneous
tissue disorders

Rash

1 (0.6)

1 (0.6)
1 (0.6)

*Investigator term: vascular pain after injection of study drug

5 WARNINGS AND PRECAUTIONS

MedDRA System Organ Class

Number of Subjects
n (%)

2 (1.2)
1 (0.6)
1 (0.6)
1 (0.6)

Nervous system disorders

Dizziness
Dysgeusia
Headache

1 (0.6)
1 (0.6)
1 (0.6)

Musculoskele tal disorders

Arthralgia
Joint swelling
Myalgia

2 (1.2)
1 (0.6)
1 (0.6)

Gastrointestinal disorders

Abdominal pain, lower
Abdominal pain, upper

1 (0.6)
1 (0.6)

8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
Animal reproductive studies have not been conducted with ELOCTATE. It is not known
whether or not ELOCTATE can cause fetal harm when administered to a pregnant woman
or can affect reproduction capacity. ELOCTATE should be given to a pregnant woman only
if clearly needed.
8.3 Nursing Mothers
It is not known whether or not ELOCTATE is excreted into human milk. Because many
drugs are excreted into human milk, caution should be exercised when ELOCTATE is
administered to a nursing woman.
8.4 Pediatric Use
Pharmacokinetic studies in children have demonstrated a shorter half-life and lower
recovery of Factor VIII compared to adults. Because clearance (based on per kg body
weight) has been shown to be significantly higher in the younger, pediatric population
(2 to 5 years of age), higher and/or more frequent dosing based on body weight may be
needed. [see Clinical Pharmacology (12.3)]
Safety and efficacy studies have been performed in 56 previously treated, pediatric
patients <18 years of age who received at least one dose of ELOCTATE as part of routine
prophylaxis, on-demand treatment of bleeding episodes, or perioperative management.
Adolescent subjects were enrolled in the adult and adolescent safety and efficacy trial,
and subjects <12 were enrolled in an ongoing pediatric trial. Twelve subjects (21%)
were <6 years of age, 31 (55%) subjects were 6 to <12 years of age, and 13 subjects
(23%) were adolescents (12 to <18 years of age). Interim pharmacokinetic data from
a pediatric study of the 38 subjects <12 years of age showed that no dose adjustment
had been required for patients ≥6 years old. Children age 2 to 5 years had a shorter halflife and higher clearance (adjusted for body weight); therefore, a higher dose or more
frequent dosing may be needed in this age group. [see Clinical Pharmacology (12.3)]
8.5 Geriatric Use
Clinical studies of ELOCTATE did not include sufficient numbers of subjects aged 65 and
over to determine whether or not they respond differently from younger subjects.

17 PATIENT COUNSELING INFORMATION

Number of Subjects
n (%)

General disorders and
Malaise
administration site conditions Chest pain
Feeling cold
Feeling hot

6.2 Immunogenicity
Clinical trial subjects were monitored for neutralizing antibodies to Factor VIII. No subjects
developed confirmed, neutralizing antibodies to Factor VIII. One 25 year old subject had a
transient, positive, neutralizing antibody of 0.73 BU at week 14, which was not confirmed
upon repeat testing 18 days later and thereafter.
The detection of antibodies that are reactive to Factor VIII is highly dependent on many
factors, including: the sensitivity and specificity of the assay, sample handling, timing of
sample collection, concomitant medications and underlying disease.

Advise the patients to:
• Read the FDA approved patient labeling (Patient Information and Instructions for Use)
• Call their healthcare provider or go to the emergency department right away if
a hypersensitivity reaction occurs. Early signs of hypersensitivity reactions may
include rash, hives, itching, facial swelling, tightness of the chest, and wheezing.
• Report any adverse reactions or problems following ELOCTATE administration to
their healthcare provider.
• Contact their healthcare provider or treatment facility for further treatment and/or
assessment if they experience a lack of a clinical response to Factor VIII therapy
because this may be a sign of inhibitor development.
44279-01

(continued)

© 2014 Biogen Idec. All rights reserved. HFE-1005760 07/14

Manufactured by:
Biogen Idec Inc.
14 Cambridge Center
Cambridge, MA 02142 USA
U.S. License # 1697
ELOCTATE™ is a trademark of Biogen Idec.
Issued June 2014

therapy was administered, or they hit
the maximum of 45 days. The outpatient
cohort was released from the hospital following chemotherapy and received supportive care in an outpatient setting until
blood cell count recovery. If readmitted,
early discharge was again possible if all of
the medical and logistic criteria were met.
Patients in the outpatient cohort had a
median 21-day recovery period (range =
2-45 days), while patients in the inpatient
cohort had a median 16-day
recovery period (range = 3-42
days).
Dr. Vaughn and colleagues
analyzed differences in the following measures:
• Early mortality
• Resource utilization, including
intensive care unit (ICU) days,
transfusions per study day,
and use of intravenous (IV)
antibiotics per study day
• Number of infections
• Total and inpatient charges
per study day, which were
compared with inpatient and
outpatient participants
During the 43 months of study
follow-up, four of the 107 outpatient participants died within
30 days of enrollment, while no
patients in the inpatient cohort
died (p=0.58). Also, nine patients
in the outpatient cohort (8%) required ICU-level care, compared
with none in the inpatient cohort
(p=0.20).
Focusing on resource use, the
researchers indicated no differences in the median number of
daily transfused red blood cell
units (0.27 for the outpatient
group vs. 0.29 for the inpatient
group; p=0.55) or transfused
platelet units (0.26 vs. 0.29 for
the inpatient group; p=0.31).
The outpatient cohort did
have more positive blood cultures compared with the inpatient group: 35 percent (n=37)
versus 14 percent (n=4; p=0.04),
though the outpatient group
had fewer IV antibiotic days per
study day compared with the
inpatient group (0.48 vs. 0.71,
respectively; p=0.01).
Overall daily health-care
charges among the two patient
groups were significantly different; those in the outpatient
program had median daily
costs of $3,840 compared with
$5,852 for the inpatient cohort
(p<0.001). “Daily charges
among early-discharge patients

November 2015