Browsing by Author "Zimran, Ari (7006390817)"

[No abstract available]

[No abstract available]

Taliglucerase alfa, the first available plant cell–expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60 U/kg every other week through 9 months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30 U/kg, n = 8; 60 U/kg, n = 9; dose adjusted, n = 2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (− 8.7, − 6.9, − 12.4 multiples of normal), liver volume (− 0.6, − 0.4, − 0.5 multiples of normal), chitotriosidase activity (− 83.1%, − 93.4%, − 87.9%), and chemokine (C[sbnd]C motif) ligand 18 concentration (− 66.7%, − 83.3%, − 78.9%), as well as mean increases in hemoglobin concentration (+ 2.1, + 2.1, + 1.8 mg/dL) and platelet count (+ 31,871, + 106,800, + 34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5 years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187. © 2016 Elsevier Inc.

Taliglucerase alfa, the first available plant cell–expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60 U/kg every other week through 9 months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30 U/kg, n = 8; 60 U/kg, n = 9; dose adjusted, n = 2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (− 8.7, − 6.9, − 12.4 multiples of normal), liver volume (− 0.6, − 0.4, − 0.5 multiples of normal), chitotriosidase activity (− 83.1%, − 93.4%, − 87.9%), and chemokine (C[sbnd]C motif) ligand 18 concentration (− 66.7%, − 83.3%, − 78.9%), as well as mean increases in hemoglobin concentration (+ 2.1, + 2.1, + 1.8 mg/dL) and platelet count (+ 31,871, + 106,800, + 34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5 years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187. © 2016 Elsevier Inc.

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 60 U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60 U/kg, respectively, reduced mean spleen volume (− 18.6 multiples of normal [MN] and − 26.0 MN), liver volume (− 0.8 MN and − 0.9 MN), and chitotriosidase activity (− 72.7% and − 84.4%), and increased mean Hb concentration (+ 2.0 g/dL and + 2.3 g/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. © 2016 Shire Human Genetic Therapies, Inc.

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 60 U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60 U/kg, respectively, reduced mean spleen volume (− 18.6 multiples of normal [MN] and − 26.0 MN), liver volume (− 0.8 MN and − 0.9 MN), and chitotriosidase activity (− 72.7% and − 84.4%), and increased mean Hb concentration (+ 2.0 g/dL and + 2.3 g/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. © 2016 Shire Human Genetic Therapies, Inc.

Ambroxol hydrochloride is an oral mucolytic drug available over-the-counter for many years as cough medicine. In 2009 it was identified as a pharmacological chaperone for mutant glucocerebrosidase, albeit in a several-fold higher dose. Unfortunately, there have been no pharma-driven clinical trials to establish its use. Thus, real-world observational data are needed on the safety and efficacy of ambroxol for patients with Gaucher disease (GD) and GBA-Parkinson disease (GBA-PD). Clinicians treating patients with ambroxol for GD and GBA-PD were approached to collaborate in an investigator-initiated registry. Anonymized data were collected, including demographics, GD type, GD-specific therapy (when applicable), adverse events (AEs), and, when available, efficacy data. We report the data of the first 41 patients (25 females) at a median (range) age 17 (1.5–74) from 13 centers; 11 with GD type 1(four diagnosed with PD), 27 with neuronopathic GD (nGD), and three GBA mutation carriers with PD. The median (range) treatment period and maximum dose of ambroxol were 19 (1–76) months and 435 (75-1485) mg/day, respectively. One patient with type 2 GD died of her disease. No other severe AEs were reported. Twelve patients experienced AE, including minor bowel discomfort, cough, allergic reaction, mild proteinuria, dizziness and disease progression. Clinical benefits were reported in 25 patients, including stable or improved neurological status, increased physical activity, and reduced fatigue. Until the approval of specific therapies for nGD and disease-modification for GBA-PD, these preliminary data may be encouraging to physicians and patients who consider an off-label use of ambroxol. © 2021 Wiley Periodicals LLC.