VPRIV Clinical Trial Design
Trials were designed to study VPRIV in treatment-naïve patients and patients previously treated with imiglucerase. This included an up-to-5-year open-label extension study of VPRIV.
VPRIV in Treatment-Naïve Patients: Studies 032 and 039
Study 032: A 12-month, randomized, double-blind, parallel-dose-group, multinational safety and efficacy study in 25 patients. Patients were required to have Gaucher disease-related anemia and either thrombocytopenia or organomegaly. Patients were not allowed to have had disease-specific therapy for at least the previous 30 months; all but one had no prior therapy. The mean age was 26 years (range 4-62), and 40% were female. Patients were randomized to receive VPRIV at a dose of either 45 U/kg (n=13) or 60 U/kg (n=12) every other week. Primary endpoint was change from baseline in hemoglobin concentration at 12 months in patients receiving 60 U/kg.1,5
Study 039: A 9-month, randomized, double-blind, active-controlled (imiglucerase), parallel-group, multinational study of VPRIV and imiglucerase in 34 patients. Patients had to have Gaucher-related anemia and either thrombocytopenia or organomegaly. Disease-specific therapy within the 12 months prior to enrollment was not allowed. The mean age was 30 years (range 3-73), and 53% were female; the youngest patient to receive VPRIV was aged 4 years. Patients were randomized to receive either 60 U/kg of VPRIV (n=17) or 60 U/kg of imiglucerase (n=17) every other week. The primary endpoint was difference in mean change from baseline to month 9 in hemoglobin concentrations between the 2 treatment groups.1,6
VPRIV in Patients Previously Treated with Imiglucerase: Study 034
Study 034: A 12-month, open-label, single-arm, multinational safety study in 40 patients who had been receiving treatment with imiglucerase at doses ranging between 15 U/kg and 60 U/kg for a minimum of 30 consecutive months. Patients were required to have a stable biweekly dose of imiglucerase for at least 6 months prior to study enrollment. The mean age was 36 years (range 9-71), and 55% were female. Imiglucerase therapy was stopped, and treatment with VPRIV was administered every other week at the same number of units as the patient’s previous imiglucerase dose. Hemoglobin concentration and platelet counts were evaluated as changes from baseline, which was defined as the end of the patient’s treatment with imiglucerase. The primary objective was to evaluate the safety of VPRIV every-other-week dosing in patients with type 1 Gaucher disease who were previously treated with imiglucerase.1,7
Study 044, an Up-to-5-Year Open-Label Extension Study
Study 044: An up-to-5-year, open-label extension study including patients from trials 032, 039, and 034. The primary objective of this study was to evaluate the long-term safety of VPRIV when given every other week. The secondary objectives were to evaluate the effect of VPRIV on hemoglobin concentrations, platelet counts, and liver and spleen volumes.1-3
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.
There are no adequate and well controlled studies with VPRIV in pregnant women and there is limited experience in pregnant women. VPRIV should be used during pregnancy only if clearly needed. 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 enzyme replacement therapies who are switching to VPRIV should continue to be monitored for antibodies to VPRIV.
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To report suspected adverse reactions, contact Shire 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 Shire Medical Information at 1-866-888-0660, option 2 or email