14 CLINICAL STUDIES
14.1 Clinical Trials of ELELYSO as Initial Therapy
Clinical Trial in Adult Patients
The safety and efficacy of ELELYSO in the treatment of adult patients with Type 1 Gaucher disease was assessed in a 9-month, multi-center, double-blind, randomized trial (Trial 1) in 31 adult 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 enzyme replacement therapy (ERT). Patients with severe neurological symptoms were excluded from the trial.
Patients were randomized to receive ELELYSO at an intravenous dosage of either 30 units/kg (n=15) (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] (n=16) every other week. After 9 months, 26 of the 31 patients continued in the blinded portion of the long-term extension trial for a total treatment duration of 24 months at the same intravenous dosage every other week. Twenty three of those 26 patients continued open-label ELELYSO treatment (30 or 60 units/kg given intravenously every other week) for an additional 12 months (total duration of ELELYSO treatment was 36 months).
Baseline Demographics
In Trial 1, patients were 19 to 74 years of age (mean age 36 years), 48% were male, 97% were White and 29% and 71% were Hispanic/Latino and non Hispanic/Latino, respectively.
Efficacy Results
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 ELELYSO treatment in Trial 1. Liver and spleen volumes were measured by MRI and are reported as percentage of body weight (%BW) and multiples of normal (MN). The observed reduction from baseline in spleen volume (the primary endpoint), was considered to be clinically meaningful in light of the natural history of untreated Gaucher disease.
| Clinical Parameter | ELELYSO 30 units/kg† (n=15) Mean (SD) | ELELYSO 60 units/kg (n=16) Mean (SD) | |
|---|---|---|---|
| |||
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) | |
The following data are the changes in clinical parameters from baseline to Month 24 (including the 9-month initial period and the 15-month first long-term extension) for the 30 units/kg (n=12) (50% of the recommended dosage) and 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] (n=14) treatment 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. The 23 patients who continued open-label ELELYSO treatment for additional 12 months demonstrated stability in these clinical parameters.
Clinical Trial in Pediatric Patients 16 Years of Age and Younger
The safety and efficacy of ELELYSO in the treatment of pediatric patients with Type 1 Gaucher disease was assessed in a 12-month, multi-center, double-blind, randomized trial (Trial 2) in 9 treatment-naïve patients. Patients were randomized to receive ELELYSO at an intravenous dosage of either 30 units/kg (n=4) (50% of the recommended dosage) or 60 units/kg (the recommended dosage) [see Dosage and Administration (2.1)] (n=5) every other week. After 12 months, all 9 patients entered a blinded portion of the long-term extension trial (24-months of total treatment) where they continued treatment with ELELYSO at the same dosage every other week.
Baseline Demographics
In Trial 2, patients were 2 to 13 years of age (mean age 8.1 years), 67% were male, 89% were White and 44% and 56% were Hispanic/Latino and non Hispanic/Latino, respectively.
Efficacy Results
The following data in Trial 2 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.
The following data are the changes [median (Q1, Q3)] in clinical parameters from baseline to Month 24 (including the initial 12-month period and the 12-month long-term extension) 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 (Trial 3). Trial 3 was a 9-month, multi-center, open-label, single arm study in patients who had been receiving intravenous 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 dosage of imiglucerase for at least 6 months prior to enrollment. 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 (9.5 units/kg to 60 units/kg given intravenously every other week). 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).
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- Eighteen of the 26 adult patients who completed the 9-month clinical trial continued treatment with ELELYSO (9.5 units/kg to 60 units/kg given intravenously every other week) in an open-label extension trial for additional 27 months (total duration of ELELYSO treatment was 36 months).
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- Five of the pediatric patients who completed the 9-month trial continued open-label treatment with ELELYSO (9.5 units/kg to 60 units/kg given intravenously every other week) for additional 24 months (total duration of ELELYSO treatment was 33 months).
Baseline Demographics
In Trial 3, patients were 6 to 66 years of age (mean age 42 years, including pediatric patients), 55% were male, 97% were White, and 16% and 84% were Hispanic/Latino and non Hispanic/Latino, respectively.
Efficacy Results
In Trial 3, 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. Mean (SD) organ volumes and hematologic values remained stable through 9 months of ELELYSO treatment. 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. The ELELYSO dosage 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.
During the 36‑month period, 18 ELELYSO-treated adult 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.
During the 33‑month period, the 5 ELELYSO‑treated pediatric patients demonstrated stability in these clinical parameters.