Clinical Registry Data

The Gaucher Registry, the largest observational database of Gaucher disease patients, is a robust source of clinical data. The registry documents the course of Gaucher disease in untreated patients and the effects of therapy in patients treated with Cerezyme and other enzyme replacement therapies. The database includes data on more than 5,600 patients receiving Cerezyme.

The Gaucher Registry is an ongoing observational database, sponsored by Genzyme, that tracks outcomes of routine clinical practice for patients with Gaucher disease.

Treatment effects observed in more than 1,000 patients with Type 1 Gaucher disease receiving Cerezyme for up to 5 years were published in The American Journal of Medicine.1 This report included data on patient responses and authors’ expectations for response with continued treatment.

The findings for patients treated with Cerezyme are as follows:

Increased hemoglobin levels

Hemoglobin levels were observed to increase rapidly during the initial 6 months of Cerezyme (imglucerace for injection) therapy, then increased more slowly over the next 6 months of therapy, reaching a plateau between 12 and 24 months1.

Increased platelet levels

Platelet levels increased in patients who had initial platelet counts of 60,000 to <120,000/mm3, 54% reached normal platelet counts after 24 months of Cerezyme treatment, Among those with initial platelet counts <60,0000/ mm3, only 16% had normal platelet counts after 24 months of therapy. However sustained responses were seen after 3 to 5 years of treatment.1

Chart 1. Increased Platelet Counts and Hemoglobin Levels in Cerezyme patients
Platelet counts and hemoglobin levels increased after treatment with Cerezyme, 2 to 5 years after treatment start. Data based on Gaucher Registry analysis.


Note: Chart above was created using data from Weinreb et al.1

 

Reduced liver volume

In 58% of patients with spleens and moderate hepatomegaly (>1.25 to 2.5 times normal), liver volumes decreased to <1.25 normal after 24 months of Cerezyme therapy. Mean liver volumes continued to decrease slightly during additional years of treatment.

Reduced spleen volume

After 24 months of therapy, 51% (22/43) of patients with moderate splenomegaly (>5 to 15 times normal), achieved spleen volumes of <5 times normal.

Chart 2. Reduced Liver and Spleen Volumes in Cerezyme Patients
Gaucher Registry data analysis shows that in 2 to 5 years of follow up after Cerezyme treatment start, there is a decrease in liver and spleen size.


Note: Chart above was created using data from Weinreb et al.1

 

Effect on Bone Disease

It has been observed in Gaucher Registry data that Cerezyme decreased the frequency of bone crises and bone pain, and improved bone mineral density in patients with documented skeletal disease.2,3 It was observed that bone pain improved as early as 3 months, bone crisis decreased within 12 months, and bone mineral density improved after 24 months with Cerezyme.2

Chart 3. Registry data on Improvement in Bone Pain and Bone Crises
Using data from the Gaucher Registry, Charrow and colleagues4 studied the effect of Cerezyme on bone pain and bone crisis in patients with Gaucher disease followed over 4 years. The study showed significant improvements in skeletal manifestations.

Figures adapted from Charrow et al.4

 

Chart 4. BMD after Approximately 8 Years
Using data from the Gaucher Registry, Wenstrup and colleagues3 compared BMD data from untreated patients to data from patients treated with Cerezyme. It was observed that on average, patients treated with Cerezyme at 60U/kg/2wks achieved a normal BMD after approximately 8 years of treatment. A significant dose-response relationship was noted.

Figures adapted from Wenstrup et al.3

 

Chart 5. Results of a 48-month Longitudinal Cohort Study
In a 48-month, open-label study of the effect of enzyme replacement therapy on bone response, Sims and colleagues2observed substantial improvements in bone pain, bone crises, and bone mineral density. They noted that Cerezyme had a positive effect on two major symptomatic manifestations of Gaucher disease—bone crises and bone pain. Mean lumbar and femoral neck DXA Z-scores significantly improved with Cerezyme treatment.

Figures adapted from Sims et al.2

 

Data from the Gaucher Registry has provided insight into Gaucher disease by supporting many published manuscripts. Each of these publications has helped to increase understanding of Gaucher disease, its natural history, diagnosis, treatment, and management as well as bone disease, pediatrics and genotypes. For more information, visit the Gaucher Registry web site. You can also see summaries of recent research at Clinical Issues in Gaucher Disease.

Indication & Usage

Cerezyme® (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions:

  1. anemia
  2. thrombocytopenia
  3. bone disease
  4. hepatomegaly or splenomegaly

Important Safety Information

Approximately 15% of patients have developed IgG antibodies to Cerezyme during the first year of therapy. Approximately 46% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity, and these patients have a higher risk of hypersensitivity. It is suggested that patients be monitored periodically for IgG antibody formation during the first year of treatment.

Hypersensitivity has also been observed in patients without detectable IgG antibodies. Symptoms suggestive of hypersensitivity have been noted in approximately 6.6% of all patients, and anaphylactoid reactions in less than 1%. Treatment with Cerezyme should be approached with caution in patients who have exhibited hypersensitivity symptoms such as pruritus, flushing, urticarial, angioedema, chest discomfort, dyspnea, coughing, cyanosis, and hypotension. Pre-treatment with antihistamines and/or corticosteroids and a reduced rate of infusion may allow continued treatment in most patients.

In less than 1% of patients, pulmonary hypertension and pneumonia have been observed during treatment with Cerezyme. These are known complications of Gaucher disease regardless of treatment. Patients with respiratory symptoms in the absence of fever should be evaluated for the presence of pulmonary hypertension.

Approximately 13.8% of patients have experienced adverse events related to treatment with Cerezyme. Some of these are injection site reactions such as discomfort, pruritus, burning, swelling or sterile abscess at the site at the site of venipuncture. Additional adverse reactions that have been reported include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Transient peripheral edema has also been reported for this therapeutic class of drug.

To report suspected adverse reactions, contact Genzyme at 800-745-4447, option 2 or FDA at 800-FDA-1088 or http://www.fda.gov/Safety/MedWatch

Please see Full Prescribing Information (PDF).

References

  1. Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher registry. Am J Med. 2002;113:112-119.
  2. Sims KB, Pastores GM, et al.. Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study. Clin Genet 200875(3):430-40.
  3. Wenstrup RJ, Kacena KA, Kaplan P, Pastores GM, Prakash-Cheng A, et al. Effect of enzyme replacement therapy with Imiglucerase on BMD in type 1 Gaucher disease. J Bone Miner Res 2007;21:119-126.
  4. Charrow J, Dulisse B, Grabowski GA,Weinreb NJ. The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1Gaucher disease. Clin Genet 2007;71:205-211.
Cerezyme has been demonstrated for over 17 years to be an effective treatment for Type 1 Gaucher disease in adults and children.