What You Don’t Know About the ACA
“n Louisiana, Medicaid expansion
I
could have saved about 500 deaths
a year. Opting out is not only a fiscal
cost but also a public health issue.”
—MARC J. KAHN, MD, MBA
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.
Vascular disorders
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
Angiopathy*
Hypertension
1 (0.6)
1 (0.6)
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)
*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)
Musculoskeletal disorders
Arthralgia
Joint swelling
Myalgia
2 (1.2)
1 (0.6)
1 (0.6)
Gastrointestinal disorders
Abdominal pain, lower
Abdominal pain, upper
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.
1 (0.6)
1 (0.6)
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)
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
who fall into this gap reside somewhere in
the South.6
“Theoretically, those people could buy
insurance without subsidies,” Ms. Gray said,
“but often their incomes are so low that they
are left without insurance.”
The authors of the Kaiser Family Foundation report echoed this point, stating that it
is unlikely that this group will be able to afford ACA coverage without one of these two
assistance programs: “In 2015, the national
average premium for a 40-year-old
individual purchasing coverage through
the Marketplace was $276 per month
for a silver plan and $213 per month
for a bronze plan, which, for people in
the coverage gap, equates to about half
of the income for those in the lower
income range … and about a quarter
of the income for those in the higher
income range.”
A Public Health Issue
Looking at the nationwide consequences
of opting out of Medicaid, a recent
Harvard study put the number of deaths
that could be potentially attributed to a
lack of Medicaid expansion in opt-out
states at between 7,000 and 17,000.7 In
states where Medicaid was expanded,
the study authors added, people with
chronic conditions who once did not
have any financial assistance with health
insurance now have increased access to
health-care services.
“In Louisiana, the study estimated
that Medicaid expansion could have
saved about 500 deaths a year,” Dr. Kahn
said. “The cost of not taking Medicaid
expansion is not only a fiscal cost but
also a public health issue.”
This is especially true for patients
with certain hematologic conditions.
“We were very hopeful for Medicaid
expansion,” said Michelle Rice, vice
president of public policy & stakeholder
relations, at the National Hemophilia
Foundation. “While the majority of
those with bleeding disorders are insured, Medicaid expansion would have
offered an option to those who remain
uninsured.” Over the past couple of
years, she noted, “we have seen a slight
increase in Medicaid enrollment in the
bleeding disorder community, from approximately 23 to 25 percent.”
However, for patients with hemophilia who fall into the coverage gaps
there is not as much hope.
“For someone with a condition like
hemophilia, treatment is not an option; it
is a necessity,” Ms. Rice sad. “So, instead of
being treated preventively, the uninsured
will likely receive their care in the emergency department. When you don’t have
insurance, you will only get treatment
when you have a bleed, which will result
in increased joint disease and will increase
the medical costs to the state.”
Even those people with hemophilia
who reside in states with the Medicaid
May 2015