Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease |
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| Authors: | D. Elstein G.M. Cohn N. Wang M. Djordjevic C. Brutaru A. Zimran |
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| Affiliation: | 1. Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel;2. Shire Human Genetic Therapies, Cambridge MA USA;3. Metabolic and Clinical Genetic Department, Mother and Child Health Care Institute, Belgrade, Serbia;4. “Sf. Ioan” Clinical and Emergency Hospital, Bucharest, Romania;1. Unité de recherche clinique appliquée (URCA), University of Montreal, Centre de Recherche, CHU Sainte-Justine, Montreal, Quebec, Canada;2. Department of Pediatrics, University of Montreal, Centre de Recherche, CHU Sainte-Justine, Montreal, Quebec, Canada;3. CSL Behring, Ottawa, Ontario, Canada;4. Department of Microbiology and Immunology, University of Montreal, Centre de Recherche, CHU Sainte-Justine, Montreal, Quebec, Canada;1. Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany;2. National Institute of Malarial Research, Indian Council of Medical Research, New Delhi, 110077, India;3. Department of Biotechnology Engineering, Institute of Engineering and Technology, Bundelkhand University, Jhansi, 284128, U.P., India;4. Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany;5. German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, 18147, Rostock, Germany;1. Pediatric Neurology, Children''s Hospital, Geneva University Hospitals, Geneva, Switzerland;2. Service of Genetic Medicine, Geneva University Hospitals, Geneva, Switzerland;3. Medical Radiology, Children''s Hospital, Geneva University Hospitals, Geneva, Switzerland;4. Pediatric Orthopedics, Children''s Hospital, Geneva University Hospitals, Geneva, Switzerland;5. Pediatric Endocrinology, Children''s Hospital, Geneva University Hospitals, Geneva, Switzerland;6. Pediatric Nephrology, Children''s Hospital, Geneva University Hospitals, Geneva, Switzerland;1. Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China;2. Shanghai Institute of Pancreatic Diseases, Shanghai, China;1. Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Brest, France;2. Etablissement Français du Sang (EFS)—Bretagne, Brest, France;3. Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest, France;1. Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, The Second Military Medical University, Shanghai, China;2. Shanghai Institute of Pancreatic Diseases, Shanghai, China |
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| Abstract: | IntroductionTherapeutic goals have been described to monitor achievement, maintenance and continuity of therapeutic response in patients with type 1 Gaucher disease receiving enzyme replacement therapy.AimTo benchmark the impact of velaglucerase alfa treatment against therapeutic goals for 5 key clinical parameters of type 1 Gaucher disease (anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology).MethodsIn an open-label Phase I/II study, twelve adults with symptomatic type 1 Gaucher disease and intact spleens received velaglucerase alfa for 9 months (60 U/kg infusion every other week [EOW]). Eleven patients completed the study and 10 enrolled in a long-term extension. After 1 year, patients who achieved ≥ 2 hematological or organ goals began step-wise dose reduction from 60 to 45 then 30 U/kg EOW. Data for anemia, thrombocytopenia, hepatomegaly, splenomegaly and skeletal pathology at baseline and 4 years are available for 8 patients (3 male, 5 female). The proportion of patients at goal for anemia, thrombocytopenia, hepatomegaly and splenomegaly at baseline was compared with the proportion achieving each goal at 4 years. The proportion achieving the skeletal pathology goal was determined on the basis of Z-score improvement from baseline to 4 years. The proportion of patients who achieved all 5 goals at 4 years was compared with the proportion at goal for all 5 parameters at baseline.ResultsAt baseline, no patient was at goal for all clinical parameters. After 1 year of treatment, all patients maintained goals present at baseline, and all achieved ≥ 2 goals. All 8 patients began step-wise dose reduction from 60 to 30 U/kg EOW between 15 and 18 months. By year 4 of treatment, all patients met goals for all 5 clinical parameters; therefore 100% achievement was seen for each of the 5 long-term, therapeutic goals.DiscussionIn this velaglucerase alfa Phase I/II and extension study, clinically meaningful achievement of each long-term, therapeutic goal was observed for each patient, despite dose reduction after 1 year. This is the first report of a cohort where all patients receiving ERT for type 1 Gaucher disease achieved all 5 of these long-term, therapeutic goals within 4 years of starting treatment and after ≥ 2 years dose reduction. |
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