Position statement: National Gaucher Foundation Medical Advisory Board, January 7, 2014

Abstract

Patients and physicians have contacted the National Gaucher Foundation regarding recent discussions and decisions by US insurance carriers and specifically United Health Care to establish a preferred status category for one of the three enzyme replacement therapies currently approved by FDA for treatment of patients with Gaucher disease. The position of the National Gaucher Foundation and its Medical Advisory Board is as follows:Imiglucerase, velaglucerase alfa, and taliglucerase alfa are bio-similar products that are not bio-identical. They are all highly purified pharmacologic recombinant human glucocerebrosidase glycoproteins produced using different technologies and derived from different cell lines: Imiglucerase (Chinese hamster ovary cell line); Velaglucerase alfa (human fibroblasts derived from a fibrosarcoma cell line); Taliglucerase (carrot root cell line). Although the conformational crystal structures of all three appear to be similar, there are minor differences in primary amino acid structure and more significant differences in glycosylation [1,2]. Globally since 1994, more than 5,000 phenotypically and genotypically diverse Gaucher disease patients have been treated with imiglucerase with an extensive observational record of efficacy and safety. Since 2010, other enzyme therapies for Gaucher disease, velaglucerase alfa, and taliglucerase, were also approved by the FDA. Randomized and observational clinical trials comprising a few hundred treatment-na€ ıve and "switch" patients suggest that during the initial 1-3 years of treatment, velaglucerase alfa and taliglucerase are arguably safe and of comparable efficacy to imiglucerase for reversing disease manifestations such as anemia, thrombocytopenia, and hepatosplenomegaly, for reduction of biomarkers and, in the case of velaglucerase alfa, for maintaining therapeutic gains in patients previously treated with imiglucerase [3][4][5][6][7][8][9][10][11][12][13][14]. Velaglucerase alfa and taliglucerase appear to reduce bone marrow Gaucher cell infiltration measured indirectly with quantitative chemical shift MRI imaging similarly to imiglucerase [8,15,16]. Compared to imiglucerase, currently published clinical trial and post-marketing data for velaglucerase alfa and taliglucerase with respect to patient-centered outcomes, such as osteopenia, osteonecrosis, fractures, need for hospitalization for splenectomy, and health-related quality of life are rudimentary [17][18][19][20][21][22][23]. Although taliglucerase is currently authorized for use only in adults, imiglucerase and velaglucerase alfa are approved for pediatric use. However, published data showing that enzyme replacement therapy (ERT) reverses Gaucher disease-associated growth and development retardation in pre-pubertal children are only available for imiglucerase [24,25]. Finally, in stable patients during the "maintenance" phase of treatment, the safety and efficacy of infusion schedules less frequent than every two weeks is supported by clinical trial evidence only for imiglucerase [26].Befor...

Stability is maintained in adults with Gaucher disease type 1 switched from velaglucerase alfa to eliglustat or imiglucerase: A sub-analysis of the eliglustat ENCORE trial

“…Currently, three enzyme therapies are available for the treatment of Gaucher disease type 1: imiglucerase (Cerezyme®, Sanofi Genzyme, first available in 1994, produced in a Chinese hamster ovary cell line), velaglucerase alfa (VPRIV®, Shire Pharmaceuticals, first available in 2010, produced in a human fibrosarcoma cell line), and taliglucerase alfa (Elelyso®, Pfizer/Protalix, first available in 2012, produced in a genetically modified carrot cell line). In addition to their different production platforms, these human recombinant acid β-glucosidase products have minor structural differences and, thus, are not considered biosimilar agents by the United States Food and Drug Administration [2] .…”

Evaluation of disease burden and response to treatment in adults with type 1 gaucher disease using a validated disease severity scoring system (DS3)

“…However, the dose tended to be somewhat higher in patients categorized as having marked disease severity based on pre-treatment DS3 score. For these response analyses, we have assumed that all commercial ERTs are bio-similar in efficacy and are freely interchangeable, although that is not yet definitively proven [ 18 ].…”

Enfermedad de Gaucher, diagnostico en el embarazo, reporte de caso y consideraciones de su tratamiento en Colombia.

“…Aunque se recomienda que la TRE se mantenga a largo plazo, en especial cuando existe organomegalia importante (20), nuestra paciente recibió solo 4 dosis adicionales Taliglucerasa en el puerperio por falta de cobertura de su asegurador y luego de 9 meses, no fue posible contactarla para seguimiento a pesar de una búsqueda activa por la red de salud regional, poniendo en evidencia algunas de las dificultades que vive la población obstetricia en los países en vías de desarrollo. Todas las instancias relacionadas con el manejo de estas pacientes debemos continuar la búsqueda de soluciones para mejorar su calidad de vida durante la maternidad.…”