"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
In Gaucher disease patients treated with 30 or 60 units/kg (N=29), pharmacokinetics were determined with the first dose and at 38 weeks.
The pharmacokinetics of taliglucerase alfa appeared to be nonlinear with a greater than dose-proportional increase in exposure at the doses studied. The median systemic clearance (CL) values were approximately 30 L/hr and 20 L/hr for 30 and 60 units/kg, respectively. The median volume of distribution at steady state (Vss) ranged from 7.30 to 11.7 L for both dose groups. At the end of infusion, taliglucerase alfa serum concentrations fell rapidly with a median terminal half life of 18.9 to 28.7 minutes for both dose groups.
No significant accumulation or change in taliglucerase alfa pharmacokinetics over time from Weeks 1 to 38 was observed with repeated doses of 30 or 60 units/kg.
Based on the limited data, there were no significant pharmacokinetic differences between male and female patients in this study.
Study 1: Trial of ELELYSO as Initial Therapy
The safety and efficacy of ELELYSO was assessed in 31 adult patients with Type 1 Gaucher disease. The trial was a 9-month multi-center, double blind, randomized study 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 naive to ERT. Patients with severe neurological symptoms were excluded from the study. Patient age ranged from 19-74 years (mean age 36 years) and 48% were male. Patients were randomized to receive ELELYSO at a dose of either 30 Units/kg (n=15) or 60 Units/kg (n=16).
At baseline, mean % body weight (%BW) and multiples of normal (MN) spleen volumes were 3.1 and 3.3 (%BW) and 15.4 and 16.7 (MN) for the 30 Units/kg and 60 Units/kg dose groups, respectively. Similarly, liver volumes were 4.2 and 3.8 (%BW) and 1.7 and 1.5 (MN). Hemoglobin concentrations were 12.2 and 11.4 g/dL and platelet counts were 75,320 and 65,038/mm3, for the 30 Units/kg and 60 Units/kg dose groups, respectively. For all studies, liver and spleen volumes were measured by MRI. The changes in clinical parameters after nine months of treatment are shown in Table 3. The observed change from baseline in the primary endpoint, spleen volume, was considered to be clinically meaningful in light of the natural history of untreated Gaucher disease.
Table 3: Mean Change from Baseline to 9 months for Clinical
Parameters in Treatment-Naive Patients with Type 1 Gaucher Disease Initiating
Therapy with ELELYSO
|Clinical Parameter||30 Units/kg (N=15)||60 Units/kg (N=16)|
|Change in Spleen Volume|| %BWMean(SD)
MN Mean (SD)
| -0.9 (0.4)
| -1.3 (1.1)
|Change in Hemoglobin g/dL||Mean (SD)||1.6 (1.4)||2.2 (1.4)|
|Change in Liver Volume|| %BWMean(SD)
MN Mean (SD)
| -0.6 (0.5)
| -0.6 (0.4)
|Change in Platelet Count /mm3||Mean (SD)||11,427 (20,214)||41,494 (47,063)|
Twenty-six previously treatment naive patients continued to be treated with ELELYSO in an extension of this study (Study 3) in a blinded manner for a total treatment duration of 24 months. For the respective 30 and 60 Units/kg groups, mean (±SD) spleen volume (%BW) decreased -1.4 (±0.6) and -2.0 (±2.0); hemoglobin increased 1.3 (±1.7) 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.
Study 2: Trial in Patients Switching from Imiglucerase to ELELYSO
The safety and efficacy of ELELYSO was assessed in 25patients 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 doses ranging from 11 Units/kg to 60 Units/kg for a minimum of 2 years. Patients also were required to be clinically stable and to have a stable biweekly dose of imiglucerase for at least 6 months prior to enrollment. Patient age ranged from 13-66 years (mean age 45 years including pediatric) and 46% 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. Adjustment of dosage was allowed by study criteria if needed in order to maintain clinical parameters (i.e., hemoglobin, platelet count, spleen volume, and liver volume). One patient required a dose increase (from 9.5 Units/kg to 19 Units/kg at week 24) for a platelet count of 92,000/mm3 at week 22, and responded with a platelet count of 170,000mm3 at month 9.
Organ volumes and hematologic values remained stable on average through 9 months of ELELYSO treatment. At baseline, spleen volume %BW was 1.1% and MN was 5.5; liver volume %BW was 2.4% and MN was 1.0; mean hemoglobin was 13.6 (± 1.57) g/dL; and mean platelet count was 160,447 (± 79,086) /mm3. At the nine month endpoint, spleen volume %BWwas 1.0% and MN was 5.1; liver volume %BW was 2.3% and MN was 0.9; mean hemoglobin was 13.4 (± 1.6) g/dL and mean platelet count was 165,654 (± 94,038) /mm3.
Last reviewed on RxList: 5/14/2012
This monograph has been modified to include the generic and brand name in many instances.
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