IMPORTANT SAFETY INFORMATION
WARNING: Life-threatening allergic reactions have occurred in some patients during VIMIZIM® (elosulfase alfa) infusions and up to 3 hours after infusion. Patients with acute respiratory illness may be at increased risk and require additional monitoring.

VIMIZIM safety and tolerability1

Summary

  • Hypersensitivity reactions, including anaphylaxis, were reported in patients treated with VIMIZIM® (elosulfase alfa) in six clinical trials; consider the risks and benefits of re-administering VIMIZIM following a severe reaction1
  • Adverse reactions were collected from 176 patients ages 5 to 57 who were enrolled in the 24-week, phase 3 pivotal study; the most common adverse reactions (≥10%) that occurred were pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue1

Adverse reactions reported by ≥10% of patients treated with VIMIZIM (2 mg/kg/wk)
and with a higher incidence than with placebo1

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Adverse reaction
VIMIZIM 2 mg/kg/wk
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 (1.7%)
Chills
6 (10.3%)
1 (1.7%)
Fatigue
6 (10.3%)
2 (3.4%)

Safety and effectiveness in pediatric patients <5 years of age has not been established and is currently being evaluated.

  • Acute reactions requiring intervention were managed by
  • Temporarily interrupting or discontinuing the infusion
  • Administering additional antihistamines, antipyretics, or corticosteroids

 

Serious adverse reactions associated with VIMIZIM are manageable with appropriate medical support.
  • Hypersensitivity reactions, including anaphylaxis, were reported in patients treated with VIMIZIM in six clinical trials; the risks and benefits of re-administering VIMIZIM following a severe reaction should be considered1,3
  • Hypersensitivity, also called a hypersensitivity reaction, is an exaggerated immune response to an antigen, resulting in local tissue injury; hypersensitivity reactions can be categorized into four types based on the mechanisms involved in the reaction and how quickly the reaction occurs after exposure to the antigen1
  • Anaphylaxis is a severe, multisystemic allergic reaction. While symptomatic severity may vary, anaphylaxis can have a rapid onset and generally affects the cutaneous, respiratory, cardiovascular, and gastrointestinal systems; anaphylaxis is a potentially fatal condition that requires immediate attention including hospitalization and an injection of epinephrine1
  • In six clinical trials, 18 of 235 (7.7%) patients treated with VIMIZIM experienced signs and symptoms consistent with anaphylaxis, including cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (eg, nausea, abdominal pain, retching, and vomiting) in conjunction with urticaria3
  • Cases of anaphylaxis have 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 infusion1
  • Due to the potential for anaphylaxis, closely observe patients during and after VIMIZIM administration; inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur1
  • In six clinical trials, 44 of 235 (18.7%) patients experienced hypersensitivity reactions including anaphylaxis; frequent symptoms of hypersensitivity reactions (occurring in more than 2 patients) included anaphylactic reactions, urticaria, peripheral edema, cough, dyspnea, and flushing1,3
  • Hypersensitivity reactions have occurred as early as 30 minutes from the start of infusion but as late as 6 days after infusion1
  • 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 reactions1
  • If severe hypersensitivity reactions occur, immediately stop the infusion of VIMIZIM and initiate appropriate treatment; because of the potential for hypersensitivity reactions, administer antihistamines with or without antipyretics prior to infusion1

Warnings, precautions, and use in special populations1
  • 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. Consider the risks and benefits of re-administering VIMIZIM following a severe reaction1
  • 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 to consider delaying the VIMIZIM infusion1
  • 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 during sleep should have these treatments readily available during infusion in the event of an acute reaction, or extreme drowsiness/sleep induced by antihistamine use1
  • Spinal/cervical cord compression (SCC) is a known and serious complication of Morquio A; in clinical trials, SCC was observed in both patients receiving VIMIZIM and patients receiving placebo1
  • Patients with Morquio A should be monitored for signs and symptoms of SCC (including back pain, paralysis of limbs below the level of compression, and urinary and fecal incontinence) and given appropriate clinical care1
  • VIMIZIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus; it is not known if VIMIZIM is present in human milk. Exercise caution when administering VIMIZIM to a nursing mother; pregnant women and nursing mothers with Morquio A who are treated with VIMIZIM should be encouraged to enroll in the Morquio A Registry Study, and they can do so by emailing MARS@bmrn.com1
  • All patients treated with VIMIZIM 2 mg/kg once per week in the placebo-controlled trial developed antidrug antibodies; the relationship between the presence of neutralizing antibodies and long-term therapeutic response could not be determined1
  • Safety and effectiveness in geriatric patients over 65 years of age has not been studied1
VIMIZIM efficacy
VIMIZIM demonstrated a statistically significant improvement in 6MWT distance at Week 24 vs placebo (P=0.0174)1
VIMIZIM administration instructions
Step-by-step instructions on how to administer VIMIZIM
Contact BioMarin RARECONNECTIONS™
Individualized support to help people with Morquio A gain access to VIMIZIM

Important Safety Information

Life-threatening anaphylactic reactions have occurred in some patients during VIMIZIM® (elosulfase alfa) 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.

Due to the potential for anaphylaxis, appropriate medical support should be readily available when VIMIZIM is administered and for an appropriate period of time following administration. In clinical trials, cases of anaphylaxis occurred as early as 30 minutes from the start of infusion and up to three hours after infusion, and as late into treatment as the 47th infusion.

In clinical trials, hypersensitivity reactions have been observed 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.

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.

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 (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.

All patients treated with VIMIZIM 2 mg/kg once per week in the placebo-controlled trial developed anti-drug antibodies. The relationship between the presence of neutralizing antibodies and long-term therapeutic response or occurrence of anaphylaxis or other hypersensitivity reactions could not be determined.

VIMIZIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if VIMIZIM is present in human milk. Exercise caution when administering VIMIZIM to a nursing mother. There is a Morquio A Registry that collects data on pregnant women and nursing mothers with MPS IVA who are treated with VIMIZIM. Contact MARS@BMRN.com for information and enrollment.

Safety and effectiveness in pediatric patients below 5 years of age have not been established and are currently being evaluated. In clinical trials, the most common adverse reactions (≥10%) occurring during infusion included pyrexia, vomiting, headache, nausea, abdominal pain, chills, and fatigue. The acute reactions requiring intervention were managed by either temporarily interrupting or discontinuing infusion, and administering additional antihistamine, antipyretics, or corticosteroids.

To report SUSPECTED ADVERSE REACTIONS contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or go to www.fda.gov/medwatch.

CONTACT US

BioMarin Pharmaceutical Inc.

Novato, CA 94949

BioMarin Medical Information: 1-800-983-4587

To report suspected adverse events email drugsafety@bmrn.com

BioMarin RareConnections™: 1-866-906-6100

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