Vimizim
Generic
Name: elosulfase alfa injection
Dosage Form: injection, solution, concentrate
Medically reviewed by
Drugs.com. Last updated on Dec 1, 2019.
WARNING: RISK OF ANAPHYLAXIS
·
Life-threatening anaphylactic reactions have occurred in
some patients during Vimizim infusions. Anaphylaxis, presenting as cough,
erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash,
dyspnea, chest discomfort, and gastrointestinal symptoms (e.g., nausea,
abdominal pain, retching, and vomiting) in conjunction with urticaria, have
been reported to occur during Vimizim infusions, regardless of duration of the
course of treatment.
·
Closely observe patients during and after Vimizim
administration and be prepared to manage anaphylaxis. Inform patients of the
signs and symptoms of anaphylaxis and have them seek immediate medical care
should symptoms occur.
·
Patients with acute respiratory illness may be at risk of
serious acute exacerbation of their respiratory compromise due to
hypersensitivity reactions, and require additional monitoring [see
Warnings and Precautions (5.1, 5.2) and Adverse Reactions (6)].
Indications
and Usage for Vimizim
Vimizim (elosulfase alfa) is
indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A
syndrome).
Vimizim
Dosage and AdministrationRecommended Dose
The recommended dose is
2 mg per kg given intravenously over a minimum range of 3.5 to 4.5 hours,
based on infusion volume, once every week. Pre-treatment with
antihistamines with or without antipyretics is recommended 30 to 60 minutes
prior to the start of the infusion [see Warnings and
Precautions (5.1)].
Parenteral drug products
should be inspected visually for particulate matter and discoloration prior to
administration, whenever solution and container permit.
Preparation Instructions
Important Information: This
product should be prepared and administered under the supervision of a
healthcare professional with the ability to manage medical emergencies.
Determine the number of
vials to be diluted based on the individual patient’s weight and the
recommended dose of 2 mg/kg.
Dilute the calculated dose
to a final volume of 100 mL or 250 mL using 0.9% Sodium Chloride Injection, USP.
The final volume is based on
the patient’s weight as follows:
· For patients who
weigh less than 25 kg, the final volume should be 100 mL;
· For patients who
weigh 25 kg or more, the final volume should be 250 mL.
The solution should be clear
to slightly opalescent and colorless to pale yellow when diluted. Do not
use if the solution is discolored or if there is particulate matter in the
solution. Note that a diluted solution with slight flocculation (e.g., thin
translucent fibers) is acceptable for administration.
Avoid agitation during
preparation. Gently rotate the bag to ensure proper distribution.
Do not shake the solution.
Administration Instructions
Administer the diluted
solution to patients using a low-protein binding infusion set equipped with a
low-protein binding 0.2 micrometer (µm) in-line filter.
Note:
The safety and effectiveness of Vimizim have not been established in pediatric
patients less than 5 years of age [see Use in Specific Populations (8.4)].
For
patients who weigh less than 25 kg:
initial infusion rate should be 3 mL per hour for the first 15 minutes
and, if tolerated, increased to 6 mL per hour for the next 15 minutes. If
this rate is tolerated, then the rate may be increased every 15 minutes in 6 mL
per hour increments, not to exceed 36 mL per hour. The total volume of the
infusion should be delivered over a minimum of 3.5 hours.
For
patients who weigh 25 kg or more:
initial infusion rate should be 6 mL per hour for the first 15 minutes
and, if tolerated, the infusion rate may be increased to 12 mL per hour for the
next 15 minutes. If this rate is tolerated, then the rate may be
increased every 15 minutes in 12 mL per hour increments, not to exceed 72 mL
per hour. The total volume of the infusion should be delivered over a
minimum of 4.5 hours.
The infusion rate may be
slowed, temporarily stopped, or discontinued for that visit in the event of
hypersensitivity reactions [see Warnings and
Precautions (5.1)]. Do not infuse
with other products in the infusion tubing. Compatibility with other
products has not been evaluated.
Storage and Stability
Vimizim does not contain
preservatives; therefore the product should be used immediately after dilution.
If immediate use is not possible, the diluted product may be stored for up to
24 hours at 2°C to 8°C (36°F to 46°F) followed by up to 24 hours at 23°C to
27°C (73°F to 81°F). Administration of Vimizim should be completed within 48
hours from the time of dilution. Vials are for single-use only. Discard any
unused product. Do not freeze or shake. Protect from light.
Dosage
Forms and Strengths
Injection: 5 mg/5 mL (1
mg/mL) in single-dose vials.
Contraindications
None
Warnings
and PrecautionsAnaphylaxis and Hypersensitivity Reactions
Anaphylaxis and
hypersensitivity reactions have been reported in patients treated with Vimizim.
In premarketing clinical trials, 18 of 235 (7.7%) patients treated with Vimizim
experienced signs and symptoms consistent with anaphylaxis. These 18 patients
experienced 26 anaphylactic reactions during infusion with signs and symptoms
including cough, erythema, throat tightness, urticaria, flushing, cyanosis,
hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms
(e.g., nausea, abdominal pain, retching, and vomiting) in conjunction with
urticaria. These cases of anaphylaxis occurred as early as 30 minutes from the
start of infusion and up to three hours after infusion. Anaphylaxis
occurred as late into treatment as the 47th infusion.
In clinical trials with
Vimizim, 44 of 235 (18.7%) patients experienced hypersensitivity reactions,
including anaphylaxis. Hypersensitivity reactions have occurred as early as 30
minutes from the start of infusion but as late as six days after infusion.
Frequent symptoms of hypersensitivity reactions (occurring in more than 2
patients) included anaphylactic reactions, urticaria, peripheral edema, cough,
dyspnea, and flushing.
Due to the potential for
anaphylaxis, appropriate medical support should be readily available when
Vimizim is administered. Observe patients closely for an appropriate period of
time after administration of Vimizim, taking into account the time to onset of
anaphylaxis seen in premarketing clinical trials. Inform patients of the signs
and symptoms of anaphylaxis, and instruct them to seek immediate medical care
should signs and symptoms occur.
Because of the potential for
hypersensitivity reactions, administer antihistamines with or without
antipyretics prior to infusion. Management of hypersensitivity reactions should
be based on the severity of the reaction and include slowing or temporary interruption
of the infusion and/or administration of additional antihistamines,
antipyretics, and/or corticosteroids for mild reactions. However, if severe
hypersensitivity reactions occur, immediately stop the infusion of Vimizim and
initiate appropriate treatment.
Consider the risks and
benefits of re-administering Vimizim following a severe reaction.
Risk of Acute Respiratory Complications
Patients with acute febrile
or respiratory illness at the time of Vimizim infusion may be at higher risk of
life-threatening complications from hypersensitivity reactions. Careful
consideration should be given to the patient’s clinical status prior to
administration of Vimizim and consider delaying the Vimizim infusion.
Sleep apnea is common in MPS
IVA patients. Evaluation of airway patency should be considered prior to
initiation of treatment with Vimizim. Patients using supplemental oxygen
or continuous positive airway pressure (CPAP) during sleep should have these
treatments readily available during infusion in the event of an acute reaction,
or extreme drowsiness/sleep induced by antihistamine use.
Spinal or Cervical Cord Compression
Spinal or cervical cord
compression (SCC) is a known and serious complication of MPS IVA and may occur
as part of the natural history of the disease. In clinical trials, SCC was
observed both in patients receiving Vimizim and patients receiving placebo.
Patients with MPS IVA should be monitored for signs and symptoms of SCC
(including back pain, paralysis of limbs below the level of compression,
urinary and fecal incontinence) and given appropriate clinical care.
Adverse
Reactions
The following serious
adverse reactions are described below and elsewhere in the labeling:
Anaphylaxis and
hypersensitivity reactions
[see Warnings and
Precautions (5.1)].Risk of acute respiratory
complications
[see Warnings and Precautions
(5.2)].Spinal or cervical cord
compression
[see Warnings and Precautions (5.3)].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 the
clinical trials of another drug and may not reflect the rates observed in
practice.
A 24-week, randomized,
double-blind, placebo-controlled clinical trial of Vimizim was conducted in
176 patients with MPS IVA, ages 5 to 57 years old. Approximately
half of the patients (49%) were male. Of the 176 patients, 65% were
White, 23% Asian, 3% Black, and 10% Other race. The majority of patients
(78%) were non-Hispanic. Patients were randomized to three treatment
groups: Vimizim 2 mg/kg once per week (n=58), Vimizim 2 mg/kg once
every other week (n=59), or placebo (n=59). All patients were treated
with antihistamines prior to each infusion.
Table 1 summarizes the most
common adverse reactions that occurred in the placebo-controlled trial with an
incidence of ≥ 10% in patients treated with Vimizim 2 mg/kg once per week and
with a higher incidence than in the placebo-treated patients.
Table
1: Adverse Reactions That Occurred in the Placebo-Controlled Trial in At Least
10% of Patients in the Vimizim 2 mg/kg Once Per Week Group and with a Higher
Incidence than in the Placebo Group
|
Adverse Reaction
|
Vimizim 2 mg/kg
once per week
|
Placebo
|
|
|
N= 58
n (%)
|
N= 59
n (%)
|
|
Pyrexia
|
19 (33%)
|
8 (14%)
|
|
Vomiting
|
18 (31%)
|
4 (7%)
|
|
Headache
|
15 (26%)
|
9 (15%)
|
|
Nausea
|
14 (24%)
|
4 (7%)
|
|
Abdominal pain
|
12 (21%)
|
1 (2%)
|
|
Chills
|
6 (10%)
|
1 (2%)
|
|
Fatigue
|
6 (10%)
|
2 (3%)
|
Extension
Trial
An open-label extension
trial was conducted in 173 patients who completed the placebo-controlled
trial [see Clinical Studies (14)]. No new adverse
reactions were reported.
Immunogenicity
As with all therapeutic
proteins, there is potential for immunogenicity. 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. For these reasons, comparison of the
incidence of antibodies in other studies or to other elosulfase alfa products
may be misleading.
All patients treated with
Vimizim 2 mg/kg once per week in the placebo-controlled trial developed
antidrug antibodies by Week 4. Anti-drug antibody titers were sustained or
increased for the duration of Vimizim treatment. Because all patients developed
anti-drug antibodies, associations between antibody titers and reductions in
treatment effect or the occurrence of anaphylaxis or other hypersensitivity
reactions could not be determined.
All patients treated with
Vimizim 2 mg/kg once per week tested positive for neutralizing antibodies
capable of inhibiting the drug from binding to the mannose-6-phosphate receptor
at least once during the trial. Binding to this receptor is required for
Vimizim to be taken into cells where it is active. Neutralizing antibody
titers were not determined in the patients. Therefore, the possibility of
an association between neutralizing antibody titer and treatment effect cannot
be assessed.
USE IN
SPECIFIC POPULATIONSPregnancy
Pregnancy Exposure Registry
There is a Morquio A
Registry that collects data on pregnant women with MPS IVA who are treated with
Vimizim. Contact [email protected] or call 1-800-983-4587 for
information and enrollment.
Risk
Summary
Available data from
published case reports and postmarketing experience with Vimizim use in
pregnant women are insufficient to evaluate for a drug-associated risk of major
birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal
reproduction studies, no effects on embryo-fetal development were observed in
rats given daily administration of elosulfase alfa up to 33 times the human
steady-state AUC (area under the concentration-time curve) at the recommended
human weekly dose premating and through the period of organogenesis. No effects
on embryo-fetal development were observed in rabbits given daily administration
of elosulfase alfa at doses up to 8 times the human steady-state AUC at the
recommended weekly dose during organogenesis, which produced maternal toxicity.
A dose-dependent increase in stillbirths was observed when elosulfase alfa was
administered daily in rats during organogenesis through lactation at doses 5
times the human steady-state AUC at the recommended human weekly dose. An
increase in pup mortality was observed at doses producing maternal toxicity.
The estimated background
risk of major birth defects and miscarriage for the indicated population is
unknown. All pregnancies have a background risk of birth defect, loss, or other
adverse outcomes. In theU.S.general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%,
respectively.
Clinical
Considerations
Disease-associated
maternal and embryo/fetal risk
Pregnancy can exacerbate
preexisting clinical manifestations of MPS and lead to adverse outcomes for
both mother and fetus.
Data
Animal
Data
All reproductive studies
with rats included pre-treatment with diphenhydramine to prevent or minimize
hypersensitivity reactions. The effects of elosulfase alfa were evaluated
based on comparison to a control group treated with diphenhydramine
alone. Daily intravenous administration of up to 20 mg/kg elosulfase alfa
in rats (33 times the human steady-state AUC at the recommended weekly dose of
2 mg/kg) during a 15-day pre-mating period, mating, and the period of
organogenesis, produced no maternal toxicity or effects on embryo-fetal
development. Daily intravenous administration of up to 10 mg/kg in
rabbits (8 times the human steady-state AUC at the recommended weekly dose)
during the period of organogenesis had no effects on embryo-fetal
development. However, maternal toxicity (gross changes in liver) was
observed in rabbits given doses of 1 mg/kg/day and higher (0.1 times the human
steady-state AUC at the recommended weekly dose). Elosulfase alfa
produced an increase in the percentage of stillbirths when administered daily
to rats at intravenous doses of 6 mg/kg and higher (5 times the human
steady-state AUC at the recommended weekly dose) during the period of
organogenesis through lactation. Daily intravenous administration of 20
mg/kg (33 times the human steady-state AUC at the recommended weekly dose)
produced maternal toxicity and an increase in mortality of offspring during the
lactation period. This study lacked a full evaluation of
neurodevelopmental milestones; however, no effects of elosulfase alfa were
noted in tests for learning and memory.
Lactation
Risk Summary
There are no data on the
presence of elosulfase alfa in human milk, the effects on the breastfed infant,
or the effects on milk production. Elosulfase alfa is present in milk from
treated rats (see Data). When a drug is
present in animal milk, it is likely that the drug will be present in human
milk. The developmental and health benefits of breastfeeding should be
considered along with the mother’s clinical need for Vimizim and any potential
adverse effects on the breastfed infant from Vimizim or from the underlying
maternal condition.
There is a Morquio A
Registry that also collects data on breastfeeding women with MPS IVA who are
treated with Vimizim. Contact [email protected] or call 1-800-983-4587 for
information and enrollment.
Data
Animal
Data
Elosulfase alfa was detected
in 1 of 5 milk samples from rat dams administered 6 mg/kg/day elosulfase alfa
and 4 of 5 milk samples from dams administered 20 mg/kg/day elosulfase alfa.
The concentration of drug in animal milk does not necessarily predict the
concentration of drug in human milk.
Pediatric Use
Safety and effectiveness of
Vimizim have been established in pediatric patients 5 years of age and
older. Use of Vimizim in patients 5 years of age and older is supported
by an adequate and well-controlled trial in pediatric and adult patients.
Clinical trials with Vimizim were conducted in 176 patients (median age 12
years, range 5 to 57 years old) with the majority of patients in the pediatric
age group (53% aged 5 to 11 years, 27% aged 12 to 17 years) [see Clinical Studies (14)]. Safety and
effectiveness in pediatric patients below 5 years of age have not been
established.
Geriatric Use
Clinical studies of Vimizim
did not include any patients aged 65 and over. It is not known whether they
respond differently from younger patients.
Vimizim
Description
Vimizim is a formulation of
elosulfase alfa, which is a purified human enzyme produced by recombinant DNA
technology in a Chinese hamster ovary cell line. Human N-acetylgalactosamine-6-sulfatase
(EC 3.1.6.4) is a hydrolytic lysosomal glycosaminoglycan-specific enzyme that
hydrolyzes sulfate from either galactose-6-sulfate or
N-acetyl-galactosamine-6-sulfate on the non-reducing ends of the
glycosaminoglycans keratan sulfate (KS) and chondroitin-6-sulfate (C6S).
Elosulfase alfa is a soluble
glycosylated dimeric protein with two oligosaccharide chains per monomer. Each
monomeric peptide chain contains 496 amino acids and has an approximate
molecular mass of 55 kDa (59 kDa including the oligosaccharides). One of
the oligosaccharide chains contains bis-mannose-6-phosphate (bisM6P). bisM6P
binds a receptor at the cell surface and the binding mediates cellular uptake
of the protein to the lysosome. Elosulfase alfa has a specific activity of
2.6 to 6.0 units/mg. One activity unit is defined as the amount of the enzyme
required to convert 1 micromole of sulfated monosaccharide substrate
D-galactopyranoside-6-sulfate (Gal-6S) to de-sulfated-galactose (Gal) and free
sulfate per minute at 37°C.
Vimizim is intended for
intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to
pale yellow, clear to slightly opalescent solution that must be diluted with
0.9% Sodium Chloride for Injection, USP prior to administration. Vimizim is
supplied in clear Type 1 glass 5 mL vials. Each vial provides 5 mg
elosulfase alfa, 31.6 mg L-arginine hydrochloride, 0.5 mg polysorbate 20,
13.6 mg sodium acetate trihydrate, 34.5 mg sodium phosphate monobasic
monohydrate, and 100 mg sorbitol in a 5 mL extractable solution with a pH
between 5.0 to 5.8. Vimizim does not contain preservatives. Each vial is for
single use only.
Vimizim -
Clinical PharmacologyMechanism of Action
Mucopolysaccharidoses
comprise a group of lysosomal storage disorders caused by the deficiency of
specific lysosomal enzymes required for the catabolism of glycosaminoglycans
(GAG). Mucopolysaccharidosis IVA (MPS IVA, Morquio A Syndrome) is characterized
by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase
activity. The sulfatase activity deficiency results in the accumulation of the
GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout
the body. The accumulation leads to widespread cellular, tissue, and organ
dysfunction. Vimizim is intended to provide the exogenous enzyme
N-acetylgalactosamine-6-sulfatase that will be taken up into the lysosomes and
increase the catabolism of the GAGs KS and C6S. Elosulfase alfa uptake by
cells into lysosomes is mediated by the binding of mannose-6-phosphate-terminated
oligosaccharide chains of elosulfase alfa to mannose-6-phosphate receptors.
In the absence of an animal
disease model that recapitulates the human disease phenotype, elosulfase alfa
pharmacological activity was evaluated using human primary chondrocytes from
two MPS IVA patients. Treatment of MPS IVA chondrocytes with elosulfase alfa
induced clearance of KS lysosomal storage from the chondrocytes.
Pharmacodynamics
The pharmacodynamic effect
of Vimizim was assessed by reductions in urinary KS levels. The relationship of
urinary KS to other measures of clinical response has not been
established [see Clinical Studies (14)]. No
association was observed between antibody development and urinary KS levels.
Pharmacokinetics
The pharmacokinetics of
elosulfase alfa were evaluated in 23 patients with MPS IVA who received
intravenous infusions of Vimizim 2 mg/kg once weekly, over approximately
4 hours, for 22 weeks. Eleven patients were aged 5 to 11 years, six were aged
12 to 17 years, and six were aged 18 to 41 years. Table 2 summarizes the
pharmacokinetic parameters at Week 0 and Week 22. Mean AUC0‑t and Cmax increased to 2.8- and
2.9-fold, respectively, at Week 22 compared to Week 0. Mean t1/2 increased from 7.5 min
at Week 0 to 35.9 min at Week 22. These changes are likely related to the
development of neutralizing antibodies in all patients.
Table
2: Pharmacokinetic Parameters
|
Pharmacokinetic Parameter
|
Week 0 (N = 22)*
Mean (SD)
|
Week 22 (N = 22)*
Mean (SD)
|
|
AUC0-t, min x µg/mL†
|
238 (100)
|
577 (416)
|
|
Cmax, µg/mL‡
|
1.49 (0.534)
|
4.04 (3.24)
|
|
Tmax, min§
|
172 (75.3)
|
202 ( 90.8)
|
|
CL, mL/min/kg¶
|
10.0 (3.73)#
|
7.08 (13.0)♠
|
|
Vdss, mL/kg♥
|
396 (316) ♦
|
650 (1842) ♠
|
|
t1/2, min♣
|
7.52
(5.48) #
|
35.9
(21.5) ♠
|
* The pharmacokinetics of elosulfase alfa was
evaluated in 23 individual patients. However, 1 patient was not tested at Week
0 and another patient was not tested at Week 22.
†AUC0-t, area under the plasma concentration-time curve from time zero
to the time of last measurable concentration;
‡Cmax, observed maximum plasma concentration;
§Tmax, time from zero to maximum plasma concentration;
¶CL, total clearance of drug after intravenous administration;
#N = 15;
♠N = 20
♥Vdss, apparent volume of distribution at steady-state;
♦N = 14;
♣t1/2, elimination half-life
Nonclinical
ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals
to evaluate carcinogenic potential or studies to evaluate mutagenic potential
have not been performed with elosulfase alfa. Based on the mechanism of
action, elosulfase alfa is not expected to be tumorigenic. Daily
intravenous administration of elosulfase alfa in rats at doses up to 20 mg/kg
(55 times the human steady-state AUC in male rats and 33 times the human
steady-state AUC in female rats at the recommended human weekly dose) had no
effects on fertility or reproductive performance.
Clinical
Studies
The safety and efficacy of
Vimizim were assessed in a 24-week, randomized, double-blind,
placebo-controlled clinical trial of 176 patients with MPS IVA. The age of
patients ranged from 5 to 57 years. The majority of the patients (82%)
presented with a medical history of musculoskeletal conditions, which includes
knee deformity (52%), kyphosis (31%), hip dysplasia (22%), prior spinal fusion
surgery (22%) and arthralgia (20%). At baseline, all enrolled patients could
walk more than 30 meters (m) but less than 325 m in six
minutes.
Patients received Vimizim
2 mg/kg once per week (n=58), Vimizim 2 mg/kg once every other week
(n=59), or placebo (n=59).
The primary endpoint was the
change from baseline in the distance walked in six minutes (six minute walk
test, 6-MWT) at Week 24. The other endpoints included changes from
baseline in the rate of stair climbing in three minutes (three-minute stair
climb test, 3-MSCT) and changes from baseline in urine KS levels at
Week 24. The treatment effect in the distance walked in 6 minutes,
compared to placebo, was 22.5 m (CI95, 4.0, 40.9; p=0.0174) in patients who received Vimizim 2 mg/kg
once per week. There was no difference in the rate of stair climbing between
patients who received Vimizim 2 mg/kg once per week and those who received
placebo. Patients who received Vimizim 2 mg/kg once every other week
performed similarly in the 6-MWT and 3-MSCT as those who received placebo. The
reduction in urinary KS levels from baseline, a measure of pharmacodynamic
effect, was greater in the Vimizim treatment groups compared to placebo.
The relationship between urinary KS and other measures of clinical response has
not been established.
Table
3: Results from Placebo-Controlled Clinical Trial
|
|
Vimizim 2 mg/kg once per week
|
Placebo
|
Vimizim vs.
Placebo
|
|
Baseline
|
Week 24
|
Change
|
Baseline
|
Week 24
|
Change
|
Mean Difference in Changes
|
|
N
|
58
|
57*
|
57
|
59
|
59
|
59
|
|
|
Six-Minute Walk Test (Meters)
|
|
Mean
± SD
Median
Min,
Max
|
203.9
± 76.32
216.5
42.4, 321.5
|
243.3
± 83.53
251.0
52.0, 399.9
|
36.5
± 58.49
20.0
-57.8, 228.7
|
211.9
± 69.88
228.9
36.2, 312.2
|
225.4
± 83.22
229.4
50.6, 501.0
|
13.5
± 50.63
9.9
-99.2, 220.5
|
23.0†
(CI95, 2.9, 43.1)
22.5‡
(CI95, 4.0, 40.9)
(p = 0.0174)‡,§
|
* One patient in the Vimizim
group dropped out after 1 infusion
† Observed Vimizim mean change – Placebo mean
change
‡ ANCOVA Model-based Vimizim mean change – Placebo
mean change, adjusted for baseline 6MWT categories (less than or equal to 200
meters, greater than 200 meters) and age groups (5-11, 12-18, 19 or older)
§ p-value based on the model-based difference in means
Extension
Trial
Patients who participated in
the placebo-controlled trial were eligible to continue treatment in an
open-label extension trial. One hundred seventy-three of 176 patients enrolled
in the extension trial in which patients received Vimizim 2 mg/kg once per week
(n=86) or Vimizim 2 mg/kg once every other week (n=87). In patients who
continued to receive Vimizim 2 mg/kg once per week for another 48 weeks
(for a total of 72-week exposure), walking ability showed no further
improvement beyond the first 24 weeks of treatment in the placebo-controlled
trial.
How
Supplied/Storage and Handling
Vimizim is supplied as a
concentrated solution for infusion (1 mg per mL) requiring dilution. One vial
of 5 mL contains 5 mg Vimizim.
NDC 68135-100-01, 5 mL
single-dose vial
Store Vimizim under
refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect
from light.
Diluted Vimizim should be
used immediately. If immediate use is not possible, diluted Vimizim may be
stored for up to 24 hours at 2°C to 8°C (36°F to 46°F) followed
by up to 24 hours at 23°C to 27°C (73°F to 81°F) during
administration.
Patient
Counseling Information
Anaphylactic Reactions
Advise the patients and
caregivers that reactions related to administration and infusion may occur
during Vimizim treatment, including life-threatening anaphylaxis.
Patients who have experienced anaphylactic reactions may require observation
during and after Vimizim administration. Inform patients of the signs and
symptoms of anaphylaxis and have them seek immediate medical care should
symptoms occur. The risks and benefits of re-administering Vimizim
following a severe reaction should be considered. Patients with acute
respiratory illness may be at risk of serious acute exacerbation of their
respiratory compromise due to hypersensitivity reactions. Pre-medication
and reduction of infusion rate may alleviate those reactions associated with
the infusion [see Warnings and Precautions (5.1, 5.2)].
Morquio
A Registry
Inform patients of the
Morquio A Registry (MARS) established in order to better understand the variability
and progression of the disease in the population as a whole, and to monitor and
evaluate longterm effectiveness and safety of Vimizim. The Morquio A Registry
will also monitor the effect of Vimizim on pregnant women, lactating women and
their infants, and determine if Vimizim is present in breast milk. Patients
should be encouraged to participate in the MARS and advised that their
participation is voluntary and may involve long-term follow-up. For more
information, contact [email protected] or call 1-800-983-4587.
Manufactured by:
BioMarin Pharmaceutical Inc. Novato,CA94949
USLicense
Number 1649
1-866-906-6100 (phone)
PACKAGE
LABEL
NDC 68135-100-01
VimizimTM
(elosulfase alfa)
Injection
5 mg/5 mL (1 mg/mL)
For intravenous infusion
Must be diluted prior to use
Rx Only
Vimizim US Vial
NDC
68135-100-01
VimizimTM
(elosulfase alfa)
5 mg/5 mL
(1 mg/mL)
For intravenous infusion
Must
be diluted prior to use
Rx Only
|
Vimizim
elosulfase alfa injection, solution, concentrate
|
|
Product
Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:68135-100
|
|
Route of
Administration
|
INTRAVENOUS
|
DEA
Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
ELOSULFASE
ALFA (ELOSULFASE
ALFA)
|
ELOSULFASE
ALFA
|
5 mg
in 5 mL
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:68135-100-01
|
1 VIAL in 1
CARTON
|
|
|
1
|
|
5 mL in 1 VIAL
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
BLA
|
BLA125460
|
02/14/2014
|
|
|
|
Labeler - BioMarin Pharmaceutical Inc. (079722386)
|
BioMarin
Pharmaceutical Inc.
