Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase

Abstract

Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB-06-002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB-06-002 who continued receiving taliglucerase alfa in extension Study PB-06-003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB-06-003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30-33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, -1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), -19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, -51.5% (±8.1%; n = 10); and CCL18 concentration, -36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment-related adverse events were mild or moderate and transient. The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661-665, 2016. © 2016 Wiley Periodicals, Inc.

© 2016 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.

Figures

Figure 1

(A) Hemoglobin concentration and (B) platelet count during long‐term treatment with taliglucerase alfa. Values are shown for each patient from baseline to last observation or through 36 total months of treatment. Mean values represent the patients who completed 36 months of treatment (n = 10).

Figure 2

(A) Spleen volume, expressed as multiples of normal (MN), where normal spleen volume is 2 mL/kg of body weight (kg), and (B) liver volume, expressed as MN, where normal liver volume is 25 mL/kg of body weight (kg), during long‐term treatment with taliglucerase alfa. Values are shown for each patient from baseline to last observation or through 36 total months of treatment. One patient was splenectomized and not included in spleen volume analysis; two patients were unable to tolerate MRI procedures and were not included in spleen volume or liver volume analyses but were followed by ultrasound. Mean values represent the patients with available data who completed 36 months of treatment (spleen, n = 7; liver, n = 8). MRI, magnetic resonance imaging.

Figure 3

Percentage change in (A) chitotriosidase activity and (B) CCL18 concentration during long‐term treatment with taliglucerase alfa. Values are shown for each patient from baseline to last observation or through 36 total months of treatment. Mean values represent the patients who completed 36 months of treatment (n = 10).