Efficacy Of Taliglucerase Alfa Research Articles

Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-naïve or previously treated with imiglucerase

Taliglucerase alfa is an enzyme replacement therapy approved for treatment of Gaucher disease (GD) in children and adults in several countries. This multicenter extension study assessed the efficacy and safety of taliglucerase alfa in pediatric patients with GD who were treatment-naïve (n=10) or switched from imiglucerase (n=5). Patients received taliglucerase alfa 30 or 60U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60U/kg, respectively, reduced mean spleen volume (−18.6 multiples of normal [MN] and −26.0MN), liver volume (−0.8MN and −0.9MN), and chitotriosidase activity (−72.7% and −84.4%), and increased mean Hb concentration (+2.0g/dL and +2.3g/dL) and mean platelet count (+38,200/mm3 and +138,250/mm3) from baseline through 36 total months of treatment. In patients previously treated with imiglucerase, these disease parameters remained stable through 33 total months of treatment with taliglucerase alfa. Most adverse events were mild/moderate; treatment was well tolerated. These findings extend the taliglucerase alfa safety and efficacy profile and demonstrate long-term clinical improvement in treatment-naïve children receiving taliglucerase alfa and maintenance of disease stability in children switched to taliglucerase alfa. Treatment was well-tolerated, with no new safety signals. This study is registered at www.clinicaltrials.gov as NCT01411228.

Long-term safety and efficacy of taliglucerase alfa in pediatric patients with Gaucher disease who were treatment-naïve previously treated with immiglucerase

CO RR EC TE D P RO OF with type 1 Gaucher disease (GD) in the United States, Israel, Australia, Canada, and other countries, and is approved for treatment of pediatric patients in the United States, Australia, and Canada, and for hematologic manifestations in pediatric patients with type III GD in Canada. Study PB-06-005 was a Phase 3B, multicenter, doubleblind, multiple-dose, randomized trial that examined the safety and efficacy of taliglucerase alfa through 12 months. Treatment-naive patients aged 2 to b18 years with GD requiring enzyme replacement therapy based on clinical condition were randomized to receive either 30 or 60 U/kg of taliglucerase alfa every other week. A total of 11 patients were allocated to taliglucerase alfa (n = 6, taliglucerase alfa 30 U/kg; n = 5, taliglucerase alfa 60 U/kg), were treated, and completed Study PB-06-005. Due to small patient numbers, there were numerical imbalances in disease parameters between the 30-U/kg and 60-U/kg groups at baseline. However, clinically, they were comparable at baseline: Patients in the 2 dose groups had similarly mild anemia, similar risks of bleeding based onplatelet count, andmuch larger than normal organ volumes. Mean percentage changes from baseline were used to compare the response between the dose groups and as a measure of control for numerical imbalances in baseline disease parameters. Results through 12months demonstrated that taliglucerase alfa 30 and 60 U/kg, respectively, increased mean hemoglobin concentration (+13.8% and +15.8%) and mean platelet count (+30.9% and +73.7%), while also reducing mean multiples of normal in spleen volume (−34.1% and−48.5%), multiples of normal in liver volume (−14.5% and −25.0%), chitotriosidase activity (−58.5% and −66.1%), and CCL18 concentration (−50.6% and −52.6%). Although statistical analysis was not possible due to the small numbers of patients, both treatment groups demonstrated clinically meaningful improvement from baseline in these disease parameters with numerically greater improvement observed in the 60-U/kg dose group. The authors wish to acknowledge fellow investigator Dr. Rene Heitner who passed away in January, 2012. This study was sponsored by Protalix BioTherapeutics. Pfizer and Protalix entered into an agreement in November 2009 to develop and commercialize taliglucerase alfa.

Markers of bone turnover in patients with type 1 Gaucher disease receiving long-term velaglucerase alfa enzyme replacement therapy

CO RR EC TE D P RO OF with type 1 Gaucher disease (GD) in the United States, Israel, Australia, Canada, and other countries, and is approved for treatment of pediatric patients in the United States, Australia, and Canada, and for hematologic manifestations in pediatric patients with type III GD in Canada. Study PB-06-005 was a Phase 3B, multicenter, doubleblind, multiple-dose, randomized trial that examined the safety and efficacy of taliglucerase alfa through 12 months. Treatment-naive patients aged 2 to b18 years with GD requiring enzyme replacement therapy based on clinical condition were randomized to receive either 30 or 60 U/kg of taliglucerase alfa every other week. A total of 11 patients were allocated to taliglucerase alfa (n = 6, taliglucerase alfa 30 U/kg; n = 5, taliglucerase alfa 60 U/kg), were treated, and completed Study PB-06-005. Due to small patient numbers, there were numerical imbalances in disease parameters between the 30-U/kg and 60-U/kg groups at baseline. However, clinically, they were comparable at baseline: Patients in the 2 dose groups had similarly mild anemia, similar risks of bleeding based onplatelet count, andmuch larger than normal organ volumes. Mean percentage changes from baseline were used to compare the response between the dose groups and as a measure of control for numerical imbalances in baseline disease parameters. Results through 12months demonstrated that taliglucerase alfa 30 and 60 U/kg, respectively, increased mean hemoglobin concentration (+13.8% and +15.8%) and mean platelet count (+30.9% and +73.7%), while also reducing mean multiples of normal in spleen volume (−34.1% and−48.5%), multiples of normal in liver volume (−14.5% and −25.0%), chitotriosidase activity (−58.5% and −66.1%), and CCL18 concentration (−50.6% and −52.6%). Although statistical analysis was not possible due to the small numbers of patients, both treatment groups demonstrated clinically meaningful improvement from baseline in these disease parameters with numerically greater improvement observed in the 60-U/kg dose group. The authors wish to acknowledge fellow investigator Dr. Rene Heitner who passed away in January, 2012. This study was sponsored by Protalix BioTherapeutics. Pfizer and Protalix entered into an agreement in November 2009 to develop and commercialize taliglucerase alfa.

Long-term safety and efficacy data of taliglucerase alfa, a Plant cell-expressed recombinant glucocerebrosidase, in the treatment of naïve Gaucher disease patients: 36-Month Results

Taliglucerase alfa is a beta-glucocerebrosidase enzyme replacement therapy (ERT) that is approved in the USA, Israel, and Uruguay for the treatment of Gaucher disease (GD) in adults, and is the first approved plant cell–expressed biotherapeutic. Pivotal study PB-06-001 was a 9-month, randomized, doubleblind, dose-ranging (30 and 60 U/kg) trial to assess the safety and efficacy of taliglucerase alfa in treatment-naive GD patients. Primary outcome measure was change from baseline in spleen volume, while secondary outcome measures included change from baseline in liver volumes, platelet counts, hemoglobin levels, and chitotriosidase activity. Key inclusion criteria were splenomegaly >8 multiples of normal (MN) and platelet counts <120,000/mm 3 . At the completion of the 9-month study, patients were eligible to enter an open-label extension study, PB-06-003, with taliglucerase alfa given every 2 weeks at the same dose as in study PB-06-001. Twenty-six treatment-naive GD patients from study PB06-001 continued double-blind treatment in study PB06-003. This interim analysis presents results for 23 patients that completed 27 months in PB-06-003 for a total of 36 months of taliglucerase alfa treatment. Mean spleen volume was reduced from 16.4/17.8 MN to 8.1/5.6 MN, liver volume was reduced from 1.7/1.5 to 1.3/1.1 MN, and chitotriosidase activity was reduced by 73.5% and 83.0% for 30 U/kg and 60 U/kg, respectively. Hemoglobin concentration and platelet counts were also improved. All treatment-related adverse events were mild or moderate in severity and transient in nature.

Plant cell-expressed recombinant glucocerebrosidase: Taliglucerase alfa as therapy for Gaucher disease in adults patients previously treated with imiglucerase: 24-month results

Taliglucerase alfa is an enzyme replacement therapy (ERT) approved in the USA, Israel, and Uruguay for adult patients with type 1 Gaucher disease (GD). Study PB-06-002 was a 9-month, phase 3, multicenter, open-label, switchover trial that evaluated safety and efficacy of taliglucerase alfa in patients with GD previously treated with imiglucerase for at least 2 years. Eligible patients entered a 12-week evaluation period to establish the stability of their disease based on hematologic parameters. For patients whose imiglucerase regimen was changed due to drug shortage, eligibility was based on historical data of disease stability. Patients with stable disease were then switched from imiglucerase to the same dose of taliglucerase alfa. Efficacy was determined by evaluation of platelet counts, hemoglobin levels, and spleen and liver volumes for clinical deterioration. The control for this study was each patient’s previous historical clinical and stability laboratory measurements. At completion of the 9-month study, patients were eligible to enter an open-label extension study, PB06-003, with taliglucerase alfa given every 2 weeks at the same dose as in study PB-06-002. This is an interim report for the 15 adult patients who have completed 24 total months of treatment. Following 24 months’ treatment with taliglucerase alfa, efficacy parameters of spleen volume, liver volume, platelet counts, hemoglobin concentration, and chitotriosidase activity were maintained or improved in these patients following switchover to taliglucerase alfa. None of the patients met the criteria for clinically relevant deteriorations as specified by the study protocol. All treatment-related adverse events were mild or moderate in severity and transient in nature.

A multicenter, double-blind, randomized safety and efficacy study of two dose levels of taliglucerase alfa in pediatric patients with Gaucher disease

In the treatment of Gaucher disease (GD), early intervention with enzyme replacement therapy (ERT) is crucial in prevention of irreversible pathology. Taliglucerase alfa is a plant cell–expressed beta-glucocerebrosidase ERT that is approved in the USA, Israel, and Uruguay for treatment of GD in adults. The aim of this multicenter, double-blind, dose-ranging (30 and 60 U/kg), 12-month study was to investigate the safety and efficacy of taliglucerase alfa in pediatric GD patients aged 2 to <18 years. Primary efficacy variable: median percent change in hemoglobin concentration from baseline. Secondary variables: percent changes in spleen/liver volumes, platelet counts, and chitotriosidase activity. After completion of the 12-month study, patients were eligible to enter a 2-year extension. Eleven patients (nine, type 1; two, type 3) were randomized to taliglucerase alfa 30 or 60 U/kg. Progressive improvement was demonstrated in hemoglobin, spleen volume, liver volume, platelet count, and chitotriosidase activity. At 12 months, composite analysis of both dose groups revealed that mean hemoglobin and platelets were increased by 14.7% and 50.3%, respectively, from baseline, and absolute spleen and liver volumes were reduced 34.2% and 9.8%, respectively, from baseline. The majority (96.2%) of adverse events (AEs) were mild or moderate, 15.1% were reported as treatment related, and one related serious AE was reported (patient continues on treatment). There were no unexpected AEs and all treatment-related AEs were transient in nature. Taken together, as previously seen for adult patients with GD, data suggest that taliglucerase alfa has the potential to provide an alternative therapy in pediatric patients.

A Multicenter, Double-Blind, Randomized Safety and Efficacy Study of Two Dose Levels of Taliglucerase Alfa in Pediatric Patients with Gaucher Disease.

AbstractAbstract 2140In the treatment of Gaucher disease (GD), early intervention with enzyme replacement therapy (ERT) is crucial in the prevention of irreversible pathology in symptomatic children. Taliglucerase alfa is a plant-cell-expressed human beta-glucocerebrosidase ERT recently approved in the United States for the treatment of adult patients with GD.The purpose of this study was to investigate the safety and efficacy of taliglucerase alfa in pediatric GD patients.This was a multicenter, double-blind, 12-month study in patients aged 2 to <18 years randomly assigned to taliglucerase alfa 30 or 60 U/kg. The primary efficacy variable was median percent change in hemoglobin concentration from baseline. Secondary variables were the percent change in spleen and liver volumes, platelet count, and chitotriosidase or CCL18. Exploratory endpoints included change in growth and development, bone disease (assessed by dual energy X-ray absorptiometry [DEXA] and occurrence of bone crises) and change in quality of life (QoL). Safety was assessed by adverse events (AEs), clinical laboratory results, echocardiography, and anti-taliglucerase alfa antibodies. After completion of the 12-month study, patients were eligible to enter a 2-year extension.A total of 11 patients (10 type 1 and 1 type 3) were randomized to taliglucerase alfa 30 or 60 U/kg. Progressive improvement was demonstrated in hemoglobin, spleen volume, liver volume, platelet count, and chitotriosidase activity. At 12 months the percent change from baseline for hemoglobin increased by 13.8% and 15.8%, platelet count increased by 30.9% and 73.7%, liver volume was reduced by 6.3% and 14.0%, spleen volume was reduced by 28.6% and 41.1%, and chitotriosidase activity was reduced by 58% and 66% for the 30 U/kg and 60 U/kg doses, respectively. The majority of the AEs were mild or moderate, 15.1% of the AEs were reported as treatment related and 1 related serious AE was reported (gastroenteritis requiring hospitalization for rehydration; the patient continues on treatment). There were no unexpected AEs and all treatment-related AEs were transient in nature.Taken together, these results suggest that taliglucerase alfa has the potential to provide an alternative therapy in pediatric patients with GD. Disclosures:Zimran:Protalix Biotherapeutics: Consultancy; Protalix Biotherapeutics: stock options, stock options Other; Protalix Biotherapeutics: Scientific Advisory Board, Scientific Advisory Board Other; Genzyme: Research Funding; Shire HGT: Honoraria; Actelion: Honoraria; Pfizer: Honoraria. Gonzalez-Rodriguez:Pfizer: Study Investigator Other. Abrahamov:Pfizer: Study Investigator Other. Elstein:Pfizer: Study Investigator Other. Heitner:Pfizer: Study Investigator Other. Paz:Protalix Biotherapeutics: Employment. Brill-Almon:Protalix Biotherapeutics, Carmiel, Israel: Employment. Chertkoff:Protalix Biotherapeutics, Carmiel, Israel: Employment.