Safety Profile of VPRIV Has Remained Consistent in Clinical Trials
The safety profile of VPRIV has remained consistent across various patient subpopulations.
Takeda has conducted clinical trials studying the safety of VPRIV in patients with type 1 Gaucher disease. The safety profile of VPRIV was similar between pediatric (ages 4-17) and adult patients; and remained consistent when further assessed during a long-term, open-label extension of Studies 032, 039, and 034 (Study 044).1-4
Safety profile of VPRIV
- The most serious, and most commonly observed, adverse reactions in 94 patients treated with VPRIV in clinical studies were hypersensitivity reactions4
- The most commonly observed symptoms of hypersensitivity reactions were headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia4
- The most common adverse reactions during clinical studies (in ≥10% of patients) were hypersensitivity reactions, headache, dizziness, pyrexia, abdominal pain, back pain, joint pain (knee), asthenia/fatigue, aPTT prolonged, and nausea4
- The safety profile of VPRIV was similar between pediatric patients and adult patients. Adverse reactions more commonly seen in pediatric patients compared with adult patients included (>10% difference) rash, aPTT prolonged, and pyrexia4
Consistent Safety Profile Across Adult and Pediatric Patients
The safety profile of VPRIV, when further assessed during a long-term, open-label extension of study 044, remained consistent, and was similar in adult and pediatric patients aged 4 years of age and older.1-3
In the overall study population (N=95):
- The primary objective was to evaluate the long-term safety of VPRIV when administered every other week2
- No new safety signals were observed among 95 patients (71 adult patients and 24 pediatric patients 4 years of age and older) over the course of this study2
- The majority of patients (>80%) experienced mild or moderate adverse events. Overall, the most common severe adverse events were osteonecrosis (3 patients) and arthralgia (2 patients)2
Serious adverse events that occurred in >1 patient included osteonecrosis (4 patients), cholelithiasis (2 patients), and arthralgia (2 patients)2
- No patient discontinued the study due to an adverse event. One patient with a prior history of seizures died due to a serious adverse event of convulsion. The investigator did not consider this death related to the study drug2
- Adverse reactions more commonly seen in pediatric patients compared with adult patients included (>10% difference) rash, aPTT prolonged, and pyrexia. Efficacy and safety have not been established in children younger than 4 years of age4
In a subset of 24 pediatric patients in the study:*
- No new safety signals were observed3
- No serious adverse events were related to treatment with VPRIV3
- No serious infusion-related adverse events occurred3
- No patient discontinued the study due to an adverse event3
- One pediatric patient tested positive for IgG anti-velaglucerase antibodies in Study 0443**
*Aged 4 years and older.
**No apparent impact was noted on the efficacy of VPRIV as assessed by changes in hemoglobin concentration and platelet count.
VPRIV® (velaglucerase alfa for injection) is indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease.
Important Safety Information
Hypersensitivity reactions, including anaphylaxis, have occurred. The most serious adverse reactions in patients treated with VPRIV (velaglucerase alfa for injection) were hypersensitivity reactions.
Hypersensitivity reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. Patients were not routinely pre-medicated prior to infusion of VPRIV. The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia. Hypersensitivity reactions in the clinical trials include any event considered related to and occurring within up to 24 hours of VPRIV infusion, including one case of anaphylaxis. Generally the reactions were mild and, in treatment-naïve patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Additional hypersensitivity reactions of chest discomfort, dyspnea, pruritus and vomiting have been reported in post-marketing experience. In some cases vomiting can be serious, requiring hospitalization and/or drug discontinuation.
As with any intravenous protein product, hypersensitivity reactions are possible, therefore, appropriate medical support, including personnel adequately trained in cardiopulmonary resuscitative measures and access to emergency measures, should be readily available when VPRIV is administered. If anaphylactic or other acute reactions occur, immediately discontinue the infusion of VPRIV and initiate the appropriate medical treatment.
Management of hypersensitivity reactions should be based on severity of the reaction, such as slowing the infusion rate, treatment with medications such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time. In cases where patients have exhibited symptoms of hypersensitivity to the active ingredient or excipients in the drug product or to other enzyme replacement therapy, pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions.
The most common adverse reactions during clinical studies (in ≥10% of patients) were hypersensitivity reactions, headache, dizziness, abdominal pain, nausea, back pain, joint pain, prolonged activated partial thromboplastin time (aPTT), fatigue/asthenia, and pyrexia. In clinical studies, the overall frequency of adverse events was generally higher in the population naïve to enzyme replacement therapy (ERT) than in the population switched from imiglucerase to VPRIV.
The safety and efficacy profiles were similar in pediatric (ages 4 to 17) and adult patients. The safety of VPRIV has not been established in patients under 4 years of age. Adverse reactions more commonly seen in pediatric patients compared to adult patients include (>10% difference): rash, aPTT prolonged, and pyrexia.
The adverse reaction profile in elderly patients was consistent with that previously observed across pediatric and adult patients. In general, dose selection for an elderly patient should be approached cautiously, considering comorbid conditions. As with all therapeutic proteins, there is a potential for immunogenicity. In clinical studies, 1 of 54 enzyme treatment-naïve patients treated with VPRIV developed IgG class antibodies (neutralizing in an in vitro assay). It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions. Patients with an immune response to other ERTs who are switching to VPRIV should continue to be monitored for antibodies to VPRIV.
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To report SUSPECTED ADVERSE REACTIONS, contact Medical Information at 1-866-888-0660, option 2 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For assistance with medical inquiries about VPRIV, please contact Medical Information at 1-866-888-0660, option 2 or email firstname.lastname@example.org.