Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant ...cell-expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the findings across six key taliglucerase alfa clinical studies. A total of 33 treatment-naïve adult patients were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 9-month, multicentre, randomized, double-blind, parallel-group, dose-comparison pivotal study, after which eligible patients continued into two consecutive extension studies; 17 treatment-naïve adult patients completed 5 total years of treatment with taliglucerase alfa. In the only ERT study focused on exclusively paediatric patients with GD, 11 treatment-naïve children were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 12-month, multicentre, double-blind study; nine completed 3 total years of treatment in a dedicated paediatric extension study. The effect of switching patients from imiglucerase to taliglucerase alfa was also investigated in a separate 9-month study that included 26 adults and five children; 10 adults completed a total of 3 years and two children completed a total of 2.75 years of taliglucerase alfa treatment in the extension studies. All studies evaluated safety and spleen volume, liver volume, platelet count, haemoglobin concentration, and biomarkers as measures of efficacy. Detailed results from baseline through the end of these studies are presented. Taliglucerase alfa was well tolerated, and adverse events were generally mild/moderate in severity and transient. Treatment with taliglucerase alfa resulted in improvements (treatment-naïve patients) or stability (patients switched from imiglucerase) in visceral, haematologic, and biomarker parameters. Together, this comprehensive data set supports the treatment of adult and paediatric patients with GD who are naïve to ERT or who have previously been treated with imiglucerase.
Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD).
Taliglucerase Alfa ...Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019.
A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients.
The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.
A multicenter, open-label, expanded-access study followed the safety of taliglucerase alfa, a plant cell–expressed recombinant enzyme replacement therapy (ERT), in adults with Gaucher disease ...previously treated with imiglucerase. Patients received taliglucerase alfa every 2 weeks for 9 months at a dose equivalent to their previous imiglucerase dose (Part A); patients were offered treatment for up to 33 months (Part B), and a later amendment allowed treatment-naïve patients.
Fifty-eight patients received taliglucerase alfa (55.2% male; mean age, 46.1 years; mean bi-weekly dose, 35.2 U/kg; mean duration, 17.8 months); 51 patients previously received ERT, seven were treatment-naïve, and 36 completed the study. Most adverse events were mild or moderate; treatment-related adverse events were mild and transient. In previously treated patients, increases from baseline to last follow-up were observed for mean ± SE hemoglobin concentration (13.0 ± 0.3 g/dL to 13.4 ± 0.2 g/dL) and platelet count (179,242 ± 15,344/mm3 to 215,242 ± 17,867/mm3). Findings were similar in treatment-naïve patients (mean ± SE hemoglobin concentration and platelet count, 12.8 ± 0.3 g/dL to 13.5 ± 0.2 g/dL and 168,821 ± 14,368/mm3 to 204,641 ± 16,071/mm3, respectively).
Taliglucerase alfa was well-tolerated for up to 33 months and demonstrated a durable therapeutic effect.
•Adverse events associated with taliglucerase alfa were mild and transient.•In patients with prior ERT, hemoglobin and platelets increased after 9 months.•In patients without prior ERT, hemoglobin and platelets improved after 9 months.•Anti-taliglucerase antibodies did not lead to loss of biologic effect in 23%.
Taliglucerase alfa, an enzyme replacement therapy (ERT) approved in several countries for the treatment of adult and pediatric patients with Type 1 Gaucher disease, is the first FDA-approved plant ...cell-expressed recombinant therapeutic protein for humans. PB-06-004 (NCT00962260) was a multicenter, open-label, expanded access study designed to follow the safety of taliglucerase alfa in patients with Gaucher disease who required ERT and who were previously treated with imiglucerase but had a dose reduction or discontinued due to a shortage of imiglucerase. Eligible patients (aged ≥18 years) with Type 1 Gaucher disease received taliglucerase alfa every 2 weeks for ³9 months at a dose equivalent to their previous imiglucerase dose, before it was reduced or discontinued (Part A), and had the option of continuing treatment for up to 33 months (Part B); a later amendment allowed treatment-naïve patients. Fifty-eight patients received treatment (55.2% male, mean age 46.1 years, mean bi-weekly dose 35.2 U/kg, mean duration 17.8 months); 51 patients previously received ERT, 7 were treatment-naïve. Thirty-six patients completed the study. Hemoglobin concentration and platelet counts were also explored. Most adverse events (AEs) were mild or moderate in severity and not related to taliglucerase alfa; treatment-related AEs were mild and transient in nature. In previously treated patients, mean (SE) hemoglobin concentration was 13.0 (0.3) g/dL at baseline, 13.4 (0.2) g/dL at 9 months, and 13.4 (0.2) g/dL at last follow-up; mean (SE) platelet count was 179,242 (15,344)/mm3 at baseline, 209,727 (17,157)/mm3 at 9 months, and 215,242 (17,867)/mm3 at last follow-up. In treatment-naïve patients, mean hemoglobin concentration and platelet counts increased. In conclusion, taliglucerase alfa was well tolerated for up to 33 months of treatment and demonstrated a durable therapeutic effect, as evidenced by stable or improved hemoglobin concentration and platelet counts in this expanded access study.
Kuter:BMS: Research Funding; Bioverativ: Consultancy, Research Funding; Rigel: Consultancy, Research Funding; Protalex: Research Funding; Novartis: Consultancy; Principia: Research Funding; Amgen Inc.: Consultancy; Argenx: Consultancy; ONO: Consultancy; Syntimmune: Consultancy; Pfizer: Consultancy; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wajnrajch:Pfizer Inc: Employment. Hernandez:Pfizer Inc: Employment. Wang:Pfizer Inc: Employment. Chertkoff:Protalix Biotherapeutics: Employment. Zimran:Pfizer Inc: Honoraria; Shire: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Genzyme: Honoraria, Research Funding.
Several studies have been done regarding the genetic susceptibility to autoimmune thyroid disease, particularly those related to the role of Major Histocompatibility Complex (MHC) genes in the ...etiology of the disease. In the present study, we report class I and class II MHC haplotypes in nine individuals affected by Hashimoto thyroiditis and Graves' disease who belong to two distinct Mexican families. In one of the families, Hashimoto thyroiditis was associated with the Human Leukocyte Antigen (HLA) HLA-DR3 allele whereas in the other family the disease was associated with homozygosity for the HLA-DR4 (DRB1*0407), HLA-DQ3 (DQB1*0302) haplotype. On the other hand, Graves' disease was found to be associated in one of the families with HLA-DR2 (DRB1*1501) and in the other with homozygosity for the HLA-DR7 (DRB*0701) and HLA-DQ2 (DQB1*0201) haplotype. These results confirm that in Mexicans as in other ethnic groups, genes located within the MHC region are related to the genetic susceptibility to develop autoimmune thyroid disease.
PURPOSE:
Glaucoma is a clinically heterogeneous disease with a pathophysiology that may include genetic susceptibility, possibly associated with an immunologic disorder. The aim of this study was to ...determine whether the DNA polymorphisms located in the HLA-DRB1 and HLA-DQB1 genes show a specific association pattern in Mexican mestizo patients with primary open-angle glaucoma.
METHODS:
This was a cross-sectional, case-control, multicenter study. We analyzed the HLA-DRB1 and DQB1 loci of 81 Mexican mestizo nonrelated patients with primary open-angle glaucoma and 98 healthy ethnic matched control subjects. Patients were diagnosed clinically and by visual fields examination. HLA typing was performed by PCR-SSO reverse dot blot.
RESULTS:
We documented increased frequencies of HLA-DRB1∗0301, DRB1∗1101, DRB1∗0701, DRB1∗1402, DQB1∗0302, and DQB1∗0301; however, none of them were significantly different from normal control subjects. Haplotype analysis showed that the HLA-DRB1∗0407-DQB1∗0302 haplotype is significantly increased in patients compared with control subjects (
P = .0001).
CONCLUSIONS:
The haplotype HLA-DRB1∗0407-DQB1∗0302 is common among Mexican mestizo (haplotype frequency = 0.102), and it was increased in our patients (haplotype frequency = 0.259,
P = .0001). This may reflect an independent association of this haplotype with the disease as the result of linkage disequilibrium or the influence of a neighboring gene. The pathophysiology of this illness is uncertain, and further studies are needed regarding the genetic susceptibility to develop primary open-angle glaucoma.
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