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Important Safety Information Prescribing Information Contact Us

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. Read more Important Safety Information

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VPRIV Efficacy by the Numbers

Efficacy of VPRIV in Treatment-Naïve Patients

In the overall population of treatment-naïve patients from Studies 032 and 039:

Mean Increase in Hemoglobin Concentration from baseline1,2

+23% at 12 months in Study 032 (n=12) P <0.0013,4

  • Mean hemoglobin concentration at baseline: 10.6 g/dL
  • Mean change from baseline to 12 months for patients receiving the 60 U/kg dose: 2.4 g/dL ± 0.3 (standard error)

+26% at 24 months in Study 044 (n=38)1,2*

  • Mean hemoglobin concentration at baseline: 11.04 g/dL
  • Mean change from baseline at 24 months: 2.75 g/dL; maintained stability vs baseline for up to 5 years
*Patients were administered VPRIV 60 U/kg every other week. N=39 at beginning of Study 044; n=34 at 12 months; n=38 at 24 months; n=37 at 36 months; n=30 at 48 months; and n=10 at 60 months.1,2

Mean Increase in Platelet Count from baseline1,2

+66% at 12 months in Study 032 (n=12) P=0.0023,4

  • Mean platelet count at baseline: 97 x 109/L
  • Mean change from baseline to 12 months for patients receiving the 60 U/kg dose:
    51 x 109/L ± 12 (standard error)

+120% at 24 months in Study 044 (n=37)1,2

  • Mean platelet count at baseline: 108.64 x 109/L
  • Mean change from baseline at 24 months: 87.85 x 109/L; maintained stability vs baseline for up to 5 years
Patients were administered VPRIV 60 U/kg every other week. N=39 at beginning of Study 044; n=32 at 12 months; n=37 at 24 months; n=34 at 36 months; n=29 at 48 months; and n=8 at 60 months.1,2

Mean Decrease in Spleen Volume from baseline1,2

-50% at 12 months in Study 032 (n=12) P=0.0033,4 

  • Mean spleen volume at baseline: 2.9% of body weight
  • Mean change from baseline to 12 months for patients receiving the 60 U/kg dose: -1.9% ± 0.5 of body weight (standard error)

-64% at 24 months in Study 044 (n=30)1,2

  • Mean spleen volume at baseline: 3.847% of body weight
  • Mean change from baseline at 24 months: -2.662% of body weight; maintained stability vs baseline for up to 5 years
Patients were administered VPRIV 60 U/kg every other week. N=39 at beginning of Study 044; n=29 at 12 months; n=30 at 24 months; n=27 at 39 months; n=20 at 51 months; and n=9 at 63 months.1,2

Mean Decrease in Liver Volume from baseline1,2

-17% at 12 months in Study 032 (n=12)3,4

The decrease was not statistically significant after adjusting for multiple tests

  • Mean liver volume at baseline: 3.6% of body weight
  • Mean change from baseline to 12 months for patients receiving the 60 U/kg dose: -0.84% ± 0.33 of body weight (standard error)

-27% at 24 months in Study 044 (n=39)1,2§

  • Mean liver volume at baseline: 4.029% of body weight
  • Mean change from baseline at 24 months: -1.206% of body weight; maintained stability vs baseline for up to 5 years
§Patients were administered VPRIV 60 U/kg every other week. N=39 at beginning of Study 044; n=36 at 12 months; n=39 at 24 months; n=36 at 39 months; n=28 at 51 months; and n=9 at 63 months.1,2

Efficacy of VPRIV in Patients Previously Treated with Imiglucerase

In the overall population of treatment-naïve patients previously treated with imiglucerase from Study 039:

Mean Increase in Hemoglobin Concentration from baseline1,2

Through 9 months of treatment in Study 039 (n=17)3,5

  • Mean hemoglobin concentration at baseline: 11.0 g/dL
  • Mean treatment difference in change from baseline to 9 months: 0.1 g/dL ± 0.4 (standard error)

After 9 months of treatment, the mean absolute increase from baseline in hemoglobin concentration was 1.6 g/dL ± 0.2 (standard error)

+20% at 24 months in Study 044 (n=16)1,2||

  • Mean hemoglobin concentration at baseline: 10.58 g/dL
  • Mean change from baseline at 24 months: 2.00 g/dL; maintained stability vs baseline for up to 48 months
||Patients were administered VPRIV 60 U/kg every other week. N=16 at beginning of Study 044; n=15 at 9 months; n=14 at 12 months; n=16 at 24 months; n=10 at 36 months; and n=5 at 48 months.1,2

Mean Increase in Platelet count from baseline1,2

Through 9 months of treatment in Study 039 (n=17)3,5

  • Mean platelet count at baseline: 171 x 109/L
  • Mean treatment difference in change from baseline to 9 months: -39 x 109/L

+134% at 24 months in Study 044 (n=15)1,2¶

  • Mean platelet count at baseline: 186.25 x 109/L
  • Mean change from baseline at 24 months: 160.94 x 109/L; maintained stability vs baseline for up to 48 months
Patients were administered VPRIV 60 U/kg every other week. N=16 at beginning of Study 044; n=15 at 9 months; n=13 at 12 months; n=15 at 24 months; n=10 at 36 months; and n=5 at 48 months.1,2

Mean Decrease in Spleen Volume from baseline1,2

Through 9 months of treatment in Study 039 (n=7)3,5

  • Mean spleen volume at baseline: 3.4% of body weight
  • Mean treatment difference in change from baseline to 9 months: 0.1% of body weight

-64% at 24 months in Study 044 (n=6)1,2#

  • Mean spleen volume at baseline: 4.702% of body weight
  • Mean change from baseline at 24 months: -3.633% of body weight; maintained stability vs baseline for up to 51 months
#Patients were administered VPRIV 60 U/kg every other week. N=16 at beginning of Study 044; n=7 at 9 months; n=4 at 12 months; n=6 at 24 months; n=2 at 39 months; and n=2 at 51 months.1,2,5

Mean Decrease in Liver Volume from baseline1,2

Through 9 months of treatment in Study 039 (n=17)3,5

  • Mean liver volume at baseline: 4.3% of body weight
  • Mean treatment difference in change from baseline to 9 months: -0.1% of body weight

-37% at 24 months in Study 044 (n=15)1,2**

  • Mean liver volume at baseline: 4.212% of body weight
  • Mean change from baseline at 24 months: -1.688% of body weight; maintained stability vs baseline for up to 51 months
**Patients were administered VPRIV 60 U/kg every other week. N=16 at beginning of Study 044; n=17 at 9 months; n=12 at 12 months; n=15 at 24 months; n=9 at 39 months; and n=8 at 51 months.1,2,5

Efficacy of VPRIV in Patients Who Switched

In the overall population of patients who switched from imiglucerase to VPRIV from Study 034:

Change in Hemoglobin Concentration from baseline2,6

Through 12 months of treatment in Study 034 (n=40)3,7

  • Median hemoglobin concentration at baseline: 13.8 g/dL
  • Median hemoglobin concentration after 12 months: 13.5 g/dL

0% at 24 months in Study 044 (n=36)2,6††

  • Mean hemoglobin concentration at baseline: 13.82 g/dL
  • Mean change from baseline at 24 months: -0.05 g/dL; maintained stability vs baseline for up to 5 years
††Patients were administered VPRIV every other week at the same dose as their previous imiglucerase dose (15-60 U/kg). N=38 at beginning of Study 044; n=36 at 12 months; n=36 at 24 months; n=16 at 36 months; n=6 at 48 months; and n=6 at 60 months.2,6

Mean Increase in Platelet count from baseline2,6

Through 12 months of treatment in Study 034 (n=40)3,7

  • Median platelet count at baseline: 162 x 109/L
  • Median platelet count after 12 months: 174 x 109/L

+8% at 24 months in Study 044 (n=35)2,6‡‡

  • Mean platelet count at baseline: 164.5 x 109/L
  • Mean change from baseline at 24 months: 9.03 x 109/L; maintained stability vs baseline for up to 5 years
‡‡Patients were administered VPRIV every other week at the same dose as their previous imiglucerase dose (15-60 U/kg). N=38 at beginning of Study 044; n=36 at 12 months; n=35 at 24 months; n=16 at 36 months; n=6 at 48 months; and n=6 at 60 months.2,6

Mean Decrease in Spleen Volume from baseline2,6

Through 12 months of treatment in Study 034 (n=36)7

  • Mean percentage change from baseline to 12 months: -5.6%
  • Median spleen volume at baseline: 2.5 multiples of normal

— Within the predefined efficacy criterion of ±15%

-8% at 24 months in Study 044 (n=34)2,6§§

  • Mean spleen volume at baseline: 0.821% of body weight
  • Mean change from baseline at 24 months: -0.110% of body weight; maintained stability vs baseline for up to 5 years
§§Patients were administered VPRIV every other week at the same dose as their previous imiglucerase dose (15-60 U/kg). N=38 at beginning of Study 044; n=34 at 12 months; n=34 at 24 months; n=13 at 39 months; n=5 at 51 months; and n=4 at 63 months.2,6

Mean Decrease in Liver Volume from baseline2,6

Through 12 months of treatment in Study 034 (n=40)7

  • Median liver volume at baseline: 0.8 multiples of normal
  • Mean percentage change from baseline to 12 months: 0.0%

— Within the predefined efficacy criterion of ±15%

-1% at 24 months in Study 044 (n=37)2,6||||

  • Mean liver volume at baseline: 2.062% of body weight
  • Mean change from baseline at 24 months: -0.026% of body weight; maintained stability vs baseline for up to 5 years
||||Patients were administered VPRIV every other week at the same dose as their previous imiglucerase dose (15-60 U/kg). N=38 at beginning of Study 044; n=37 at 12 months; n=37 at 24 months; n=15 at 39 months; n=6 at 51 months; and n=5 at 63 months.2,6


One Exploratory Efficacy Objective

In the 044 analysis of the 032 and 039 populations, efficacy of VPRIV in improving bone mineral density (BMD) Z-score was assessed as an exploratory efficacy objective.1

STUDY LIMITATIONS

  • These data were from an exploratory objective from an open-label extension study and had less evidetiary value than primary and secondary objectives. Further confirmatory studies are required to draw any conclusions from these data.1
  • Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DXA) of the lumbar spine in patients over 18 years of age. Drifts in calibration can occur in individual scanners over time, as can breakpoints. Longitudinal quality assurance (QA) data were collected from the scanners and corrective calculations were made, if needed. A post hoc cross-calibration of DXA scanners was necessary to pool study data collected from multiple centers, and this increased the likelihood of detecting a possible treatment effect. Where sites were missing QA data, an assumption of no drift was made, which may have affected the accuracy of the DXA results.1

Mean change over time in lumbar spine BMD from baseline
(baseline was before the first dose in the initial trials).1

*Error bars show 95% confidence intervals. Clinical significance of these data is unknown.

At 24 months in Study 044:1

+0.62 SD mean increase in BMD Z-score in the lumbar spine (n=31)

  • Median BMD Z-score at baseline: -1.73 SD (-4.20, 0.78)1

* Data shown above exclude patients previously treated with imiglucerase from Trial 039.1

Of the 31 patients in this analysis, 4 patients used bisphosphates during the initial trial, the extension study or both. Bisphosphonates affect bone turnover and BMD.1

Note: Mean change in femoral neck BMD Z-score was not statistically significant.1

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Indication

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.

Please see Full Prescribing Information.

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 medinfous@shire.com.

References