Brand Name
Vimizim
Generic Name
Elosulfase
View Brand Information FDA approval date: February 14, 2014
Classification: Hydrolytic Lysosomal Glycosaminoglycan-specific Enzyme
Form: Injection
What is Vimizim (Elosulfase)?
Vimizim is indicated for patients with Mucopolysaccharidosis type IVA . Vimizim is a hydrolytic lysosomal glycosaminoglycan -specific enzyme indicated for patients with Mucopolysaccharidosis type IVA .
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Brand Information
VIMIZIM (elosulfase alfa)
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS and RISK OF ACUTE RESPIRATORY COMPLICATIONS
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.
Initiate VIMIZIM in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue VIMIZIM and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to 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
1INDICATIONS AND USAGE
VIMIZIM (elosulfase alfa) is indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).
2DOSAGE FORMS AND STRENGTHS
Injection: 5 mg/5 mL (1 mg/mL) as a clear to slightly opalescent and colorless to pale yellow solution in a single-dose vial.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following serious adverse reactions are described below and elsewhere in the labeling:
- Hypersensitivity Reactions Including Anaphylaxis
- Risk of Acute Respiratory Complications
- Spinal or Cervical Cord Compression
4.1Clinical 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 3 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.
Extension Trial
An open-label extension trial was conducted in 173 patients who completed the placebo-controlled trial
4.2Immunogenicity
As with all therapeutic proteins, including VIMIZIM, 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 anti-drug 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.
5DESCRIPTION
Elosulfase alfa 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 (elosulfase alfa) injection is a sterile, preservative-free, nonpyrogenic, clear to slightly opalescent, colorless to pale yellow solution for intravenous infusion after dilution. Each single-dose vial contains 5 mL solution of 5 mg elosulfase alfa, 31.6 mg arginine hydrochloride, 34.5 mg monobasic sodium phosphate, 0.5 mg polysorbate 20, 8.2 mg sodium acetate, and 100 mg sorbitol in Water for Injection, USP with a pH between 5 to 5.8.
6CLINICAL 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 (CI
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.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
VIMIZIM (elosulfase alfa) injection is supplied as a sterile, preservative-free, clear to slightly opalescent, clear to pale yellow solution in a single-dose vial. Each vial contains 5 mg/5 mL (1 mg/mL) of elosulfase alfa. VIMIZIM is available as:
One single-dose vial in a carton (NDC 68135-100-01)
8PATIENT COUNSELING INFORMATION
Hypersensitivity Reactions Including Anaphylaxis
Advise the patient or caregiver that life-threatening hypersensitivity reactions, including anaphylaxis may occur with VIMIZIM treatment.
Advise the patient or caregiver that anaphylaxis has occurred during the early course of enzyme replacement therapy and after 1extended duration of therapy.
Inform the patient or caregiver of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis, and to seek immediate medical care should symptoms occur. The risks and benefits of re-administering VIMIZIM following a severe reaction should be considered
9PRINCIPAL DISPLAY PANEL - 5 mL Vial Carton
NDC 68135-100-01
Vimizim
Injection
5 mg/5 mL (1 mg/mL)
For Intravenous Infusion
One 5 mL Single-dose vial
Rx Only
BiOMARIN
