Healthcare Professional

The Paediatric Resource Centre is a free service by Elsevier for healthcare professionals in Australia and New Zealand only.

You are here

Taliglucerase Alfa Improves or Stabilises Parameters of Gaucher Disease in Children and Adolescents

Dr Zimran - Speaker World Symposium 2017Ari Zimran, MD

February 18, 2017—San Diego, California—Comprehensive data covering six clinical trials support taliglucerase alfa treatment of adult and paediatric patients with Gaucher disease who are naive to enzyme replacement therapy or who have previously been treated with imiglucerase.

This finding of results of six key, randomised clinical trials of taliglucerase alfa in treatment-naive patients with Gaucher disease was presented at the 13th Annual WORLDSymposium, from February 13–18.

Ari Zimran, MD, of the Gaucher Clinic, Shaare Zedek Medical Center, Hebrew University and Hadassah Medical School, Jerusalem, Israel, explained that taliglucerase alfa is an enzyme replacement therapy approved for adult and paediatric patients with type 1 Gaucher disease in several countries. Taliglucerase alfa is the first plant cell-expressed recombinant therapeutic protein approved by the FDA for humans.

Gaucher disease is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids.

Gaucher disease type 1 (non-neuropathic) is the most common and least severe form of the disease. Symptoms may begin early in life or in adulthood and mainly affect the liver, spleen, and bone. Enlarged liver and grossly enlarged spleen (together hepatosplenomegaly) are common; the spleen can rupture and cause additional complications.

Type 1 (N370S homozygote) occurs mainly in Ashkenazi Jews, at 100 times the occurrence in the general populace. The incidence of Gaucher disease is about one in 20,000 live births. Approximately one in 100 persons in the general US population is a carrier of type 1 Gaucher disease, a prevalence of one in 40,000. Among Ashkenazi Jews, the rate of carriers is considerably higher, at roughly one in 15.

The median age at diagnosis is 28 years of age, and life expectancy is mildly decreased. No neurological symptoms have been observed.

Skeletal weakness and bone disease may be extensive. Spleen enlargement and bone marrow replacement cause anaemia, thrombocytopenia, and leukopenia. The brain and nervous system are not affected pathologically, but lung and, rarely, kidney impairment may occur.

Patients in this group usually bruise easily (due to low levels of platelets) and experience fatigue due to low numbers of red blood cells. Depending on disease onset and severity, type 1 patients may live well into adulthood. The range and severity of symptoms can vary dramatically between patients.

Dr. Zimran and colleagues reported findings across six key taliglucerase alfa clinical studies. Taliglucerase alfa, one of the four glucocerebrosidases, was approved in 2012.

Thirty-three adult treatment-naive patients were randomised to taliglucerase alfa 30 or 60 units per kilogram of body weight in a 9-month, multicentre, randomised, double-blind, parallel-group, dose-comparison pivotal trial.

After the trial, eligible patients continued into two consecutive extension trials. Seventeen treatment-naive adult patients completed five total years of treatment with taliglucerase alfa.

In the only trial of enzyme replacement therapy focused on exclusively paediatric patients with Gaucher disease, 11 treatment-naive children were randomised to taliglucerase alfa 30 or 60 units per kilogram of body weight 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 trial that included five children and 26 adults. Two children completed a total of 2.75 years and 10 adults completed a total of 3 years of taliglucerase alfa treatment in the extension studies.

All trials evaluated safety and spleen volume, liver volume, platelet count, haemoglobin concentration, and biomarkers as measures of efficacy.

Taliglucerase alfa was well tolerated, and adverse events were generally mild/moderate in severity and transient. Treatment with taliglucerase alfa resulted in improvements (treatment-naive patients) or stability (patients switched from imiglucerase) in visceral, haematologic, and biomarker parameters.

Dr. Zimran concluded that these comprehensive data covering six clinical trials support the treatment of adult and paediatric patients with Gaucher disease who are naive to enzyme replacement therapy or who have previously been treated with imiglucerase.

Paediatric Resource Centre

The Paediatric Resource Centre is dedicated to offering you free access to specially selected peer-reviewed articles, editor’s perspectives, expert interviews, and conference news to keep you informed of the latest developments in the diagnosis, management and treatment of patients with paediatric disorders. These include metabolic disorders and lysosomal storage diseases such as Fabry disease, Pompe disease, Gaucher disease and mucopolysaccharidoses, among others. Led by an Editorial Board of internationally recognised experts Associate Professor Maria Fuller and Dr Katrina Dipple, the Paediatric Resource Centre is editorially independent and freely available to healthcare professionals in Australia and New Zealand. This Resource Centre is hosted by the highly regarded Elsevier journal Molecular Genetics and Metabolism.

Sign-up for e-alerts on new content

Don't miss out on new content. Sign-up to receive email alerts when new content becomes available on the Paediatric Resource Centre.

About the journal

Molecular Genetics and Metabolism is a contribution to the understanding of the metabolic basis of disease. The journal publishes articles describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, occasional minireviews reporting timely advances as well as brief communications and letters to the editor are considered.


Sanofigenzymeonline on paediatrics

The Paediatric Resource Centre is funded by Sanofi Genzyme and developed by Elsevier. Sanofi Genzyme has no editorial control over the content of this Resource Centre. The Resource Centre and all content therein has been subject to an independent editorial review. The content expressed are those of the individual experts and the editorial board governed by Elsevier and do not necessarily express the view of Sanofi Genzyme.