A team of researchers recently discussed the recommended uses of the drug eliglustat in American adults suffering from Gaucher disease type 1 (GD1). These findings, “Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States,” were published as a mini review in Molecular Genetics and Metabolism.
Affecting around 1 in 40,000 to 1 in 60,000 people in the United States and Europe, GD1 is an inherited disease caused by mutations in the glucocerebrosidase gene resulting in deficient acid β-glucosidase, an enzyme that cleaves glucocerebrosides through hydrolysis.
This leads to a buildup of glucosylceramide and glucosylsphingosine in organs like the spleen, liver, bone marrow, and the lung. In turn, this induces a number of health problems such as anemia, thrombocytopenia, growth issues, lung disease, immune dysfunction, bone pain, osteoporosis, vertebral compression fractures, and bone infarction.
A number of therapeutic approaches have been used to correct GD1. This includes enzyme replacement therapy (ERT) based on recombinant human acid β-glucosidase (imiglucerase), which has been considered the standard of care for more than 20 years for GD1. Another treatment based on substrate reduction therapy (SRT) is believed to work by inhibition of glucosylceramide synthase.
The authors reviewed the STR-based drug eliglustat, developed by Genzyme and approved by the FDA in August 2014 for a treatment of GD1. “There are important pharmacotherapeutic differences between ERT and eliglustat that impact clinical management. Over the past 25 years, physicians have become familiar with ERT and published clinical guidelines for its effective use. With the exception of participants in the clinical trials, most physicians who currently treat patients with GD1 are relatively unacquainted with eliglustat,” the authors wrote.
They summarized a set of recommendations formulated during a meeting sponsored by Genzyme and presented by experts in Gaucher disease and eliglustat from clinical trials:
1) Eliglustat's properties are still not fully understood and require further investigation, and patients treated with the drug should be monitored.
2) Eliglustat was approved for patients with varying CYP2D6 function, a category of enzymes called cytochrome P450 involved in the metabolism. Eliglustat is suitable for poor metabolizer with low or no CYP2D6 function, intermediate metabolizers, and extensive metabolizer with normal CYP2D6 function.
3) Eliglustat dosage is defined by the status of CYP2D6 metabolizer.
4) If the patient is treated with other drugs metabolized by CYP2D6 and CYP3A (another cytochrome P450 responsible for drug metabolism), the dosage should be adapted accordingly.
“Infusion of ERT has been the mainstay of GD care for more than 20 years and will continue to be the therapy of choice for many patients and physicians," the authors concluded. "With the approval of eliglustat as a first-line therapy, eligible GD1 patients now have the option of a daily oral therapy. It will be critical that physicians carefully assess individual patients to determine their appropriateness for eliglustat therapy."
A summary of the additional considerations and assessments for eliglustat patients is provided in the inset, the authors wrote.