For injection: 400 units of imiglucerase as a white to off-white lyophilized powder in a single-dose vial for reconstitution.

None.

The following clinically significant adverse reactions are described elsewhere in the labeling:

Imiglucerase is a hydrolytic lysosomal glucocerebrosidase-specific enzyme. It is an analogue of the human enzyme b-glucocerebrosidase (b-D-glucosyl-N-acylsphingosine glucohydrolase, E.C. 3.2.1.45), produced by recombinant DNA technology using mammalian cell culture (Chinese hamster ovary). Purified imiglucerase is a monomeric glycoprotein of 497 amino acids, containing 4 N-linked glycosylation sites (Mr=60,430). Imiglucerase differs from placental glucocerebrosidase by one amino acid at position 495, where histidine is substituted for arginine. The oligosaccharide chains at the glycosylation sites have been modified to terminate in mannose sugars. The modified carbohydrate structures on imiglucerase are somewhat different from those on placental glucocerebrosidase.

CEREZYME (imiglucerase) for injection is intended for intravenous use. It is supplied as a sterile, nonpyrogenic, white to off-white lyophilized powder for reconstitution with Sterile Water for Injection, USP. Each single-dose vial contains 424 units imiglucerase, mannitol (340 mg), polysorbate 80, NF (1.06 mg), and sodium citrates: disodium hydrogen citrate (36 mg) and trisodium citrate (104 mg).

An enzyme unit (U) is defined as the amount of enzyme that catalyzes the hydrolysis of 1 micromole of the synthetic substrate para-nitrophenyl-b-D-glucopyranoside (pNP-Glc) per minute at 37°C. Reconstituted solutions have a pH of approximately 6.1.

Study 1 was a randomized, double-blind, active-controlled clinical trial that enrolled 30 patients (17 male and 13 female) with Type 1 Gaucher disease. Patient ages ranged from 12 to 69 years, with a mean age of 38 years in the CEREZYME treatment group and a mean age of 28 years in the alglucerase treatment group at baseline. The inclusion criteria required patients to have a hemoglobin level of at least 1 g/dL below the lower limit of the normal range for their respective age and sex. Patients were randomized 1:1 to receive either CEREZYME 60 units/kg administered intravenously every other week or alglucerase for 6 months.

In Study 1, the primary efficacy parameters were an increase in hemoglobin concentration (at least 1 g/dL) and platelet count and a decrease in spleen and liver volume at 6 months. Efficacy results are shown in Table 3.

In Study 1, bone x-rays showed improvements in cortical thickness and lucencies in 7 of 11 CEREZYME-treated patients.

In Study 2, an open-label extension study of Study 1, 29 patients with Type 1 Gaucher disease continued their assigned treatment for an additional 18 months. Patients were unblinded 3 months into Study 2 and those on alglucerase were allowed to cross-over to CEREZYME treatment. After total treatment duration of CEREZYME for 18–24 months, mean increase from baseline of Study 1 in hemoglobin was 2.4 g/dL, mean increase in platelet count was 40 ×10

The efficacy of CEREZYME for the treatment of non-CNS manifestations of Type 1 and Type 3 Gaucher disease was assessed in Study 3, an observational study, using data from the International Collaborative Gaucher Group (ICGG) Gaucher Disease Registry (NCT00358943). Study 3 included patients with Type 1 or Type 3 Gaucher disease who were treated with CEREZYME as initial therapy with an index clinical assessment and one or more follow-up clinical assessments. Study 3 was a baseline-controlled analysis in patients with Type 1 Gaucher disease (19 weeks to 87 years of age) and patients with Type 3 Gaucher disease (7 weeks to 54 years of age) who received CEREZYME intravenously as prescribed by their physicians (initiated treatment between 1992–2021). After approximately two years (1 to 3 years) of CEREZYME treatment in patients with Type 1 and 3 Gaucher disease, mean changes from baseline in the following measures showed improvement: hemoglobin, platelet count, liver volume, spleen volume, and height Z-score.

The 2-year summaries include measurements within 1 to 3 years after treatment initiation due to the lack of predefined data collection timepoints in the registry.

CEREZYME (imiglucerase) for injection is supplied as a white to off-white lyophilized powder in a carton containing one single-dose vial: NDC 58468-4663-1. Each vial contains 400 units of imiglucerase. CEREZYME does not contain any preservatives.

Advise patients and caregivers that life-threatening hypersensitivity reactions, including anaphylaxis, and IARs may occur with CEREZYME treatment.

Advise patients and caregivers that anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy.

Inform patients and caregivers of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis, and IARs and to seek immediate medical care should symptoms occur

Inform patients and caregivers that the Gaucher patient registry has been established in order to better understand the variability and progression of Gaucher disease and to continue to monitor and evaluate long-term treatment effects of CEREZYME. A pregnancy sub-registry will also monitor the effects of CEREZYME on pregnant women and their offspring

NDC 58468-4663-1

Cerezyme

400 units per vial

For intravenous infusion after

sanofi