"The National Institutes of Health has launched DS-Connect, a Web-based health registry that will serve as a national health resource for people with Down syndrome and their families, researchers, and health care providers.
Mechanism Of Action
Gaucher disease is an autosomal recessive disorder caused by mutations in the human glucocerebrosidase gene, which results in a reduced activity of the lysosomal enzyme glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency results in accumulation of substrate glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or “Gaucher cells,” which accumulate in the liver, spleen and bone marrow.
ELELYSO is a recombinant analog of human lysosomal glucocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, reducing the amount of accumulated glucocerebroside. ELELYSO uptake into cellular lysosomes is mediated by binding of ELELYSO mannose oligosaccharide chains to specific mannose receptors on the cell surface leading to internalization and subsequent transport to the lysosomes.
Pharmacokinetics of taliglucerase alfa were evaluated in 38 patients (29 adult and 9 pediatric patients) who received intravenous infusions of ELELYSO 30 units/kg or 60 units/kg every other week. ELELYSO 30 units/kg is not a recommended dose in treatment-na´ve Gaucher disease patients [see DOSAGE AND ADMINISTRATION]. The pharmacokinetic parameters in adult and pediatric patients are summarized in Table 3.
In adult Type 1 Gaucher disease patients treated with ELELYSO 30 units/kg or 60 units/kg (N=29) every other week as initial therapy, pharmacokinetics were determined with the first dose and at Week 38 of treatment. The pharmacokinetics of taliglucerase alfa appeared to be nonlinear with a greater than dose-proportional increase in exposure at the doses studied.
No significant accumulation or change in taliglucerase alfa pharmacokinetics over time from Weeks 1 to 38 was observed with repeated dosages of 30 units/kg or 60 units/kg every other week. Based on the limited data, there were no significant pharmacokinetic differences between male and female patients in this study.
Pharmacokinetics of taliglucerase alfa were evaluated in 9 pediatric patients 4 to 17 years of age with Type 1 Gaucher disease who were treated with ELELYSO for 10 to 27 months. Six of the 9 patients were treatment-na´ve, and 3 patients were switched from imiglucerase. In both the 30 units/kg and 60 units/kg dose groups, clearance values in pediatric patients were similar to those in adult patients. AUC values in pediatric patients were lower than AUC values in adult patients, due to weight-based dosing of taliglucerase alfa and lower body weights in pediatric patients.
Table 3: Taliglucerase Alfa Pharmacokinetic Parameters
after Repeated Dosing in Adult and Pediatric Patients with Type 1 Gaucher
(N=9) Median (Range)
|Adult Patients at Week 38
(N=29) Median (Range)
n = 5
n = 4
n = 14
n = 15
|an = 14
bValues were derived from concentration data expressed in ng/mL
Clinical Trials Of ELELYSO As Initial Therapy
Clinical Trial in Patients 19 Years and Older
The safety and efficacy of ELELYSO were assessed in 31 adult patients with Type 1 Gaucher disease. The trial was a 9-month, multi-center, double-blind, randomized trial in patients with Gaucher disease-related enlarged spleens ( > 8 times normal) and thrombocytopenia ( < 120,000 /mm³). Sixteen patients had enlarged livers and ten patients had anemia at baseline. All patients were na´ve to ERT. Patients with severe neurological symptoms were excluded from the trial. Patients were 19 to 74 years of age (mean age 36 years), and 48% were male. Patients were randomized to receive ELELYSO at a dosage of either 30 units/kg (n=15) or 60 units/kg (n=16) every other week. The recommended dosage in treatment-na´ve adult patients is 60 units/kg every other week. ELELYSO 30 units/kg every other week is not a recommended dosage [see DOSAGE AND ADMINISTRATION].
Table 4 shows the baseline values and mean (±SD) changes in clinical parameters (spleen volume, liver volume, platelet count, and hemoglobin) after 9 months of treatment with ELELYSO. For all clinical trials, liver and spleen volumes were measured by MRI and are reported as percentage of body weight (%BW) and multiples of normal (MN). The observed change from baseline in the primary endpoint, reduction in spleen volume, was considered to be clinically meaningful in light of the natural history of untreated Gaucher disease.
Table 4: Mean (SD) Changes in Clinical Parameters from
Baseline to 9 Months in Treatment-Na´ve Adults with Type 1 Gaucher Disease
Initiating Therapy with ELELYSO (N=31)
|Clinical Parameter||30 Units/kg*
|Spleen Volume (% BW)||Baseline||3.1 (1.5)||3.3 (2.7)|
|Month 9||2.2 (1.3)||2.1 (1.9)|
|Change||-0.9 (0.4)||-1.3 (1.1)|
|Spleen Volume (MN)||Baseline||15.4 (7.7)||16.7 (13.4)|
|Month 9||11.1 (6.3)||10.4 (9.4)|
|Liver Volume (% BW)||Baseline||4.2 (0.9)||3.8 (1.0)|
|Month 9||3.6 (0.7)||3.1 (0.7)|
|Change||-0.6 (0.5)||-0.6 (0.4)|
|Liver Volume (MN)||Baseline||1.7 (0.4)||1.5 (0.4)|
|Month 9||1.4 (0.3)||1.2 (0.3)|
|Change||-0.2 (0.2)||-0.3 (0.2)|
|Platelet Count (mm³)||Baseline||75,320 (40,861)||65,038 (28,668)|
|Month 9||86,747 (50,989)||106,531 (53,212)|
|Change||11,427 (20,214)||41,494 (47,063)|
|Hemoglobin (g/dl)||Baseline||12.2 (1.7)||11.4 (2.6)|
|Month 9||14.0 (1.4)||13.6 (2.0)|
|Change||1.6 (1.4)||2.2 (1.4)|
|*The recommended ELELYSO dosage in treatment-na´ve adult patients is 60 units/kg every other week. ELELYSO 30 units/kg every other week is not a recommended dosage. [see DOSAGE AND ADMINISTRATION]|
Twenty-six of the 31 patients in this clinical trial continued blinded treatment with ELELYSO in an extension trial for a total treatment duration of 24 months. The following data are the changes in clinical parameters from baseline to Month 24 for the 30 units/kg (n=17) and 60 units/kg (n=14) dose groups, respectively: mean (SD) spleen volume (%BW) decreased -1.4 (0.6) and -2.0 (2.0); hemoglobin increased 1.3 (0.7) g/dL and 2.4 (2.3) g/dL; liver volume (%BW) decreased -1.1 (0.5) and -1.0 (0.7); and platelet count increased 28,433 (31,996) /mm³ and 72,029 (68,157) /mm³ .
Clinical Trial in Patients 16 Years and Younger
The safety and efficacy of ELELYSO were assessed in 9 pediatric patients with Type 1 Gaucher disease. The trial was a 12-month, multi-center, double-blind, randomized study in treatment-na´ve patients. Patients were 2 to 13 years of age (mean age 8.1 years), and 67% were male. Patients were randomized to receive ELELYSO at a dosage of either 30 units/kg (n=4) or 60 units/kg (n=5) every other week. The recommended ELELYSO dosage in treatment-na´ve pediatric patients is 60 units/kg every other week. ELELYSO 30 units/kg every other week is not a recommended dosage [see DOSAGE AND ADMINISTRATION].
Mean (±SD) baseline spleen volume for the 60 units/kg dose group was 29.4 (±24.3) MN, and decreased to 12.9 (±7.2) MN at 12 months. Baseline liver volume for the 60 units/kg dose group was 2.2 (±0.5) MN, and decreased to 1.7 (±0.3) MN at 12 months. Mean (±SD) platelet count for the 60 units/kg dose group was 99,600 (±42,899)/mm³ at baseline, and increased to 172,200 (±89,290)/mm³ at 12 months.
Clinical Trial In Patients Switching From Imiglucerase Treatment To ELELYSO
The safety and efficacy of ELELYSO were assessed in 31 patients (26 adult and 5 pediatric patients) with Type 1 Gaucher disease who were switched from imiglucerase to ELELYSO. The trial was a 9-month, multi-center, open-label, single-arm study in patients who had been receiving treatment with imiglucerase at dosages ranging from 9.5 units/kg to 60 units/kg every other week for a minimum of 2 years. Patients were required to be clinically stable and have a stable biweekly dose of imiglucerase for at least 6 months prior to enrollment. Patients were 6 to 66 years of age (mean age 42 years, including pediatric patients), and 55% were male. Imiglucerase therapy was stopped, and treatment with ELELYSO was administered every other week at the same number of units as each patient's previous imiglucerase dose. If needed, adjustment of dosage was allowed during the study in order to maintain stability of clinical parameters (i.e., spleen volume, liver volume, platelet count, and hemoglobin).
Mean (±SD) organ volumes and hematologic values remained stable through 9 months of ELELYSO treatment. At baseline, spleen volume was 5.2 (±0.9) MN, liver volume was 1.0 (±0.1) MN, platelet count was 161,137 (±73,387)/mm³, and hemoglobin was 13.5 (±1.4) g/dL. After 9 months of ELELYSO treatment, spleen volume was 4.8 (±0.9) MN, liver volume was 1.0 (±0.0) MN, platelet count was 161,167 (±80,820)/mm³, and hemoglobin was 13.4 (±1.5) g/dL. ELELYSO dose remained unchanged in 30 of 31 patients. One patient required a dose increase at Week 24 (from 9.5 units/kg to 19 units/kg) for a platelet count of 92,000/mm³ at Week 22, which subsequently increased to 170,000/mm³ at Month 9.
Last reviewed on RxList: 9/5/2014
This monograph has been modified to include the generic and brand name in many instances.
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