14 CLINICAL STUDIES
14.1 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 naïve 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-naïve 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 (2.1)].
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.
|Clinical Parameter||30 units/kg† (n=15)|
|60 units/kg (n=16)|
|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)|
|Change||-4.5 (2.1)||-6.6 (5.4)|
|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)|
Twenty-six of the 31 patients in this 9-month 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=12) and 60 units/kg (n=14) dose groups, respectively: mean (SD) spleen volume (%BW) decreased by 1.4 (0.6) and 2.0 (2.0), in MN by 6.8 (3.0) and 10.2 (9.8); hemoglobin increased by 1.3 (1.7) g/dL and 2.4 (2.3) g/dL; liver volume (%BW) decreased by 1.1 (0.5) and 1.0 (0.7), in MN by 0.4 (0.2) and 0.4 (0.3 and platelet count increased 28,433 (31,996) /mm3 and 72,029 (68,157) /mm3. Twenty-three of the 26 patients who continued open-label treatment with ELELYSO for additional 12 months demonstrated stability in these clinical parameters.
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-naïve 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-naïve 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 (2.1)].
The following data are the changes [median (Q1, Q3)] in clinical parameters from baseline to Month 12 for the 60 units/kg dose group (n=5): spleen volume decreased from 18.4 (14.2, 35.1) MN to 11.0 (8.3, 14.5) MN; hemoglobin increased from 11.1 (9.2, 11.3) g/dL to 11.7 (11.5, 12.9) g/dL; liver volume decreased from 2.1 (2.0, 2.3) MN to 1.6 (1.5, 1.9) MN; platelet count increased from 80,000 (79,000, 87,000)/mm3 to 131,000 (119,000, 215,000)/mm3.
Nine pediatric patients in the 12-month 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 [median (Q1, Q3)] in clinical parameters from baseline to Month 24 for the 60 units/kg dose group (n=5): spleen volume decreased by 19.0 (8.3, 41.2) MN; hemoglobin increased by 2.5 (1.9, 3.0) g/dL; liver volume decreased by 0.8 (0.6, 1.1) MN; and platelet count increased by 76,000 (67,000, 100,000)/mm3.
14.2 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 (4.5) MN, liver volume was 1.0 (0.3) 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 (4.6) MN, liver volume was 1.0 (0.2) 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.
Eighteen of the 26 adult patients who completed the 9-month clinical trial continued treatment with ELELYSO in an open-label extension trial for additional 27 months (total treatment 36 months). Patients maintained stability in clinical parameters (spleen volume, liver volume, platelet count and hemoglobin); however only 10 of 18 adult patients completed 27 months of ELELYSO treatment in the extension trial and only 7 patients had their spleen and liver volumes assessed at 36 months.
Five pediatric patients in the 9-month clinical trial who continued open-label treatment with ELELYSO for additional 24 months demonstrated stability in these clinical parameters.