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Imiglucerase in the treatment of Gaucher disease: a history and perspective.

ABSTRACT: The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease.

SUBMITTER: Deegan PB

PROVIDER: S-EPMC3340106 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Imiglucerase in the treatment of Gaucher disease: a history and perspective.

Deegan Patrick B PB Cox Timothy M TM

Drug design, development and therapy 20120418

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, wer ...[more]

PMID: 22563238

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Project description:BACKGROUND:Gaucher disease (GD) type I is the most common type of GD. Its main clinical manifestations are hepatosplenomegaly as well as bone and hematological abnormalities. The objective of the present study was to perform a literature review on the growth and metabolism of GD type I patients. METHODS:We searched Pubmed and Scielo.br databases with predetermined study limits: case series (n?5), clinical trials, systematic reviews, and meta-analyses, and enzyme replacement therapy (ERT) with alglucerase or imiglucerase. The outcomes of interest were the following: growth and development, weight, height, malnutrition, overweight, obesity, basal metabolism, hypermetabolism, insulin resistance, and diabetes. A total of 175 articles were found, of which 28 met the inclusion criteria; these articles were grouped into three central themes: 1) growth of children and adolescents before and after ERT; 2) metabolic changes that remained during ERT; and 3) changes in metabolic status resulting from the treatment. RESULTS AND DISCUSSION:The articles included in the present literature review are very heterogeneous, which hinders the analysis of data. They indicated that GD patients usually show low weight and height before ERT, which are improved with treatment in children and adolescents. Studies evaluating the energy metabolism by indirect calorimetry have indicated that the disease is associated with hypermetabolism. In adults, some changes in energy metabolism remain on ERT, and alterations, such as insulin resistance, seem to be associated with the treatment. It is not clear which are the required doses of imiglucerase for obtaining an adequate cost-effective relation, as well as the advisable therapeutic measures to avoid possible long-term adverse effects related to ERT. CONCLUSIONS:ERT tends to normalise the growth of children and adolescents with GD type I, it seems to cause a partial response in relation to some metabolic changes associated with the disease, and it can causes metabolic changes such as weight gain in adult patients. Therefore, additional research is necessary.

Project description:BackgroundFractures in Gaucher disease type 1 (GD1) patients cause significant morbidity. Fracture risk may be decreased by enzyme replacement therapy (ERT) but not eliminated. When considering initiation of treatment, it is useful to know to what extent fixed patient-specific factors determine risk for future fractures beyond standard risk factors that change with time and treatment, such as decreased bone mineral density. We developed a tool called the GRAF score (Gaucher Risk Assessment for Fracture) that applies 5 widely available characteristics (sex, age at treatment initiation [ATI], time interval between diagnosis and treatment initiation, splenectomy status, history of pre-treatment bone crisis) and provides a practical method to assess future fracture risk when imiglucerase ERT is initiated.MethodsInclusion criteria: GD1 patients in the International Collaborative Gaucher Group Gaucher Registry as of September 2019 initially treated with alglucerase/imiglucerase; known splenectomy status; at least one skeletal assessment on treatment (3216 of 6422 patients). Data were analyzed by ATI group (< 18, ≥ 18 to < 50, or ≥ 50 years of age) using Cox proportional hazards regression with all 5 risk factors included in the multivariable model. A composite risk score was calculated by summing the contribution of each parameter weighted by the strength of its association (regression coefficient) with fracture risk.ResultsPatients were followed from the date of treatment initiation (or age 18 years for patients if treatment started earlier) to the date of first adult fracture (n = 288 first fracture endpoints), death, or end of follow-up. The GRAF score for each ATI group was associated with a 2.7-fold increased risk of adult fracture for each one-point increase (p < 0.02 for < 18 ATI, p < 0.0001 for ≥ 18 to < 50 ATI and ≥ 50 ATI).ConclusionsThe GRAF score is a tool to be used with bone density and other modifiable, non-GD-specific risk factors (e.g. smoking, alcohol intake, frailty) to inform physicians and previously untreated GD1 patients about risk for a future fracture after starting imiglucerase regardless of whether there is an eventual switch to an alternative ERT or to substrate reduction therapy. GRAF can also help predict the extent that fracture risk increases if initiation of treatment is further delayed.

Dataset Information

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

Publications

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

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