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REBINYN ®
Coagulation Factor IX (Recombinant), GlycoPEGylated
Rx Only
BRIEF SUMMARY: Please consult package insert for full prescribing
information
INDICATIONS AND USAGE: REBINYN ® , Coagulation Factor IX (Recombinant),
GlycoPEGylated, is a recombinant DNA-derived coagulation Factor IX concentrate indicated
for use in adults and children with hemophilia B for: On-demand treatment and control of
bleeding episodes; Perioperative management of bleeding. Limitations of Use: REBINYN ® is
not indicated for routine prophylaxis in the treatment of patients with hemophilia B. REBINYN ®
is not indicated for immune tolerance induction in patients with hemophilia B.
CONTRAINDICATIONS: REBINYN ® is contraindicated in patients who have known
hypersensitivity to REBINYN ® or its components (including hamster proteins)
WARNINGS AND PRECAUTIONS: Hypersensitivity Reactions: Allergic-type
hypersensitivity reactions, including anaphylaxis, are possible with REBINYN ® . The product
may contain traces of hamster proteins which in some patients may cause allergic reactions.
Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema,
chest tightness, difficulty breathing, wheezing, urticaria, and itching. Observe patients for
signs and symptoms of acute hypersensitivity reactions, particularly during the early phases
of exposure to the product. Discontinue use of REBINYN ® if allergic- or anaphylactic- type
reactions occur, and initiate appropriate treatment. Inhibitors: The formation of inhibitors
(neutralizing antibodies) to Factor IX may occur during Factor replacement therapy in the
treatment of hemophilia B. Monitor all patien ts using clinical observations and laboratory
tests for the development of inhibitors. An association between the development of Factor IX
inhibitors and allergic reactions has been reported. Evaluate patients experiencing allergic
reactions for the presence of an inhibitor. Patients with Factor IX inhibitors may be at an
increased risk of severe allergic reactions with subsequent exposure to Factor IX. Thrombotic
Events: The use of Factor IX-containing products has been associated with thrombotic
complications. Due to the potential risk of thrombotic complications, monitor patients for
early signs of thrombotic and consumptive coagulopathy when administering this product
to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of
thrombosis or disseminated intravascular coagulation (DIC). In each of these situations, the
benefit of treatment with REBINYN ® should be weighed against the risk of these complications.
Nephrotic Syndrome: Nephrotic syndrome has been reported following immune tolerance
induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors,
often with a history of allergic reactions to Factor IX. The safety and efficacy of using REBINYN ®
for immune tolerance induction have not been established. Monitoring Laboratory Tests:
If monitoring of Factor IX activity is performed, use a chromogenic assay or selected one-stage
clotting assay validated for use with REBINYN ® . The one-stage clotting assay results can be
significantly affected by the type of activated partial thromboplastin time (aPTT) reagent used,
which can result in over- or under-estimation of Factor IX activity. Avoid the use of silica-
based reagents, as some may overestimate the activity of REBINYN ® . If a validated one-stage
clotting or chromogenic assay is not available locally, then use of a reference laboratory is
recommended. If bleeding is not controlled with the recommended dose of REBINYN ® , or if the
expected Factor IX activity levels in plasma are not attained, then perform a Bethesda assay to
determine if Factor IX inhibitors are present.
ADVERSE REACTIONS: Common adverse reactions (incidence ≥ 1%) reported in clinical
trials for REBINYN ® were itching and injection site reactions. Clinical Trials Experience:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials
of another drug and may not reflect the rates observed in clinical practice. During the clinical
development program, 115 previously treated male patients received at least one dose of
REBINYN ® . A previously treated patient was defined as a subject with a history of at least 150
exposure days to other Factor IX products (adolescent/adult subjects) or 50 exposure days to
other Factor IX products (pediatric subjects), and no history of inhibitors. There were a total of
8801 exposure days, equivalent to 170 patient-years. A total of 40 patients (35%) were treated
for more than 2 years. Adverse reactions are shown in Table 3.
Table 3: Summary of Adverse Reactions in Previously Treated Patients
System Organ Class
Adverse Reaction
Number of subjects (%)
General disorders and
Injection site reactions 4 (4)
administration site conditions
Immune system disorders
Hypersensitivity
1 (1)
Skin and subcutaneous tissue
Itching
3 (3)
disorders
Immunogenicity: Subjects were monitored for inhibitory antibodies to factor IX prior to
dosing, on a monthly basis for the first three months, every two months up to one year, every
three months for an additional year, and then every 6 months until end of trial. No inhibitors
were reported in the clinical trials in previously treated patients. In an ongoing trial in previously
untreated patients, anaphylaxis has occurred with development of a factor IX inhibitor following
treatment with REBINYN ® . Inhibitor development and anaphylactic reactions are more likely
to occur during the early phases of factor IX replacement therapy. The detection of antibody
formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the
observed incidence of antibody (including neutralizing antibody) positivity in an assay may be
influenced by several factors, including assay methodology, sample handling, timing of sample
collection, concomitant medications, and underlying disease. Neurologic Considerations:
Animals administered repeat doses of REBINYN ® showed accumulation of PEG in the choroid
plexus. The potential clinical implications of these animal findings are unknown. The physician
should consider whether the patient may be vulnerable, such as infants and children who have
developing brains and patients who are cognitively impaired. Physician’s discretion is advised
with regard to neurocognitive assessments, taking into consideration factors such as duration
of use, cumulative dose, age of the patient and related comorbidities that are likely to increase
the risks to patients. Adverse neurologic reactions should be reported.
USE IN SPECIFIC POPULATIONS: Pregnancy: Risk Summary: There are no data with
REBINYN ® use in pregnant women to determine whether there is a drug-associated risk.
Animal reproduction studies have not been conducted with REBINYN ® . It is unknown whether
REBINYN ® can cause fetal harm when administered to a pregnant woman or can affect fertility.
REBINYN ® should be given to a pregnant woman only if clearly needed. In the U.S. general
population, the estimated background risk of major birth defect and miscarriage in clinically
recognized pregnancies is 2-4% and 15-20%, respectively. Lactation: Risk Summary:
There is no information regarding the presence of REBINYN ® in human milk, the effect on the
breastfed infant, and the effects on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for REBINYN ® and
any potential adverse effects on the breastfed infant from REBINYN ® or from the underlying
maternal condition . Pediatric Use: Safety and efficacy of REBINYN ® were evaluated in 43
previously treated pediatric patients. Twelve of these subjects (28%) were 1 to 6 years of age;
13 subjects (30%) were 7 to 12 years of age; and 18 subjects (42%) were 13 to 17 years of age.
Pharmacokinetic parameters were evaluated for 28 of these subjects who were treated with
REBINYN ® 40 IU/kg. No difference in the safety profile of REBINYN ® was observed between
previously treated pediatric subjects and adult subjects. Body weight-adjusted clearance was
higher for pediatric subjects than for adult subjects. Fixed doses were studied in the clinical
trials and no dose adjustment was required for pediatric subjects. Twenty-eight of the forty-
three previously treated pediatric subjects (1 to 17 years old) were treated with REBINYN ® for
137 bleeding episodes. Results are provided in Table 4.
Table 4: Efficacy in treatment of bleeding episodes in pediatric subjects by age
≤ 6 years 7-12 years 13-17 years
n=11
n=31
n=95*
New bleeding episodes
Efficacy assessment**
Excellent or good
10 (91%)
29 (94%)
91 (97%)
Moderate or poor
1 (9%)
2 (6%)
3 (3%)
Number of injections to treat a bleeding
episode
1 injection
9 (82%)
27 (87%)
78 (82%)
2 injections
1 (9%)
4 (13%)
12 (13%)
> 2 injections
1 (9%)
–
5 (5%)
*Efficacy assessment was missing for one bleeding episode.
**Efficacy assessment [Response] was assessed according to a four-point scale using:
Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within
8 hours after a single injection; Good: Noticeable pain relief and/or improvement in signs
of bleeding within 8 hours after a single injection; Moderate: Probable or slight beneficial
effect within the first 8 hours after the first injection but requiring more than one injection
within 8 hours; Poor: No improvement, or worsening of symptoms within 8 hours after the
second of two injections.
Animals administered repeat doses of REBINYN ® showed accumulation of PEG in the choroid
plexus. The potential clinical implications of these animal findings are unknown. No adverse
neurologic effects of PEG have been reported in infants, children, and adolescents exposed to
REBINYN ® during clinical trials. The potential consequences of long term exposure have not
been fully evaluated. Geriatric Use: Clinical studies of REBINYN ® did not include sufficient
numbers of subjects age 65 and over to determine whether or not they respond differently than
younger subjects. Animals administered repeat doses of REBINYN ® showed accumulation
of PEG in the choroid plexus. The potential clinical implications of these animal findings
are unknown. No adverse neurologic effects of PEG have been reported in adults exposed to
REBINYN ® during clinical trials, however use in older adults with baseline cognitive dysfunction
has not been fully evaluated.
More detailed information is available upon request.
Version: 1
REBINYN ® and MixPro ® are trademarks of Novo Nordisk A/S.
For Patent Information, refer to:
http://novonordisk-us.com/patients/products/product-patents.html
For information contact:
Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA
1-844-REB-INYN
Manufactured by: Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark
© 2017 Novo Nordisk
USA17BIO02000 7/2017