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Diana Karpman, Peter Höglund
Orphan drugs designed to treat rare diseases are often overpriced per patient. Novel treatments are sometimes even more expensive for patients with ultra-rare diseases, in part due to the limited number of patients. Pharmaceutical companies that develop a patented life-saving drug are in a position to charge a very high price, which, at best, may enable these companies to further develop drugs for use in rare disease. However, is there a limit to how much a life-saving drug should cost annually per patient? Government interventions and regulations may opt to withhold a life-saving drug solely due to its high price and cost-effectiveness...
October 13, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Antonio Pisani, Dario Bruzzese, Massimo Sabbatini, Letizia Spinelli, Massimo Imbriaco, Eleonora Riccio
BACKGROUND: In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-analysis of existing data. METHODS: Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015...
September 8, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Hiroaki Wakakuri, Shunichi Nakamura, Kouichi Utsumi, Wataru Shimizu, Masahiro Yasutake
Fabry disease, an X-linked lysosomal storage disorder due to α-galactosidase A deficiency, is associated with dysfunction of various cell types and results in a systemic vasculopathy. We describe a 29-year-old woman with Fabry disease presenting with severe cardiac and renal manifestations. Gene analysis demonstrated a novel mutation (K391E) in the GLA gene. Enzyme replacement therapy (ERT) was started with agalsidase-β after confirming the diagnosis of Fabry disease, resulting in normalization of LV systolic function and improvement of renal function...
September 28, 2016: International Heart Journal
Daniel Oder, Peter Nordbeck, Christoph Wanner
Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies...
2016: Nephron
Robert J Hopkin, Gustavo Cabrera, Joel Charrow, Roberta Lemay, Ana Maria Martins, Michael Mauer, Alberto Ortiz, Manesh R Patel, Katherine Sims, Stephen Waldek, David G Warnock, William R Wilcox
BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death. METHODS: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events...
September 2016: Molecular Genetics and Metabolism
Regina El Dib, Huda Gomaa, Raíssa Pierri Carvalho, Samira E Camargo, Rodrigo Bazan, Pasqual Barretti, Fellype C Barreto
BACKGROUND: Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers.This is an update of a Cochrane review first published in 2010, and previously updated in 2013. OBJECTIVES: To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease...
2016: Cochrane Database of Systematic Reviews
Christoph Kampmann, Amandine Perrin, Michael Beck
No abstract text is available yet for this article.
2016: Orphanet Journal of Rare Diseases
Ozlem Goker-Alpan, Nicola Longo, Marie McDonald, Suma P Shankar, Raphael Schiffmann, Peter Chang, Yinghua Shen, Arian Pano
BACKGROUND: Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. METHODS: In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life...
2016: Drug Design, Development and Therapy
Olivier Lidove, Frédéric Barbey, Dau-Ming Niu, Eva Brand, Kathleen Nicholls, Svetlana Bizjajeva, Derralynn A Hughes
Baseline demographic and phenotypic characteristics of patients aged ≥50years in the Fabry Outcome Survey (Shire; data extracted June 2014) were compared with younger adults to investigate potential factors influencing treatment decisions in later life. Age groups were defined using age at treatment initiation or at FOS entry for untreated patients: 18-49 (n=1344; 49.5% male; 64.6% received agalsidase alfa enzyme replacement therapy [ERT]); 50-64 (n=537; 35.4% male; 74.3% treated); 65-74 (n=137; 32.1% male; 68...
August 2016: Molecular Genetics and Metabolism
Rannveig Skrunes, Einar Svarstad, Kristin Kampevold Larsen, Sabine Leh, Camilla Tøndel
BACKGROUND: Agalsidase-α 0.2 mg/kg every other week (eow) and agalsidase-β 1.0 mg/kg/eow are licensed in Europe as equipotent treatment of the α-galactosidase deficiency in Fabry disease. This case series describes the effects of agalsidase dose adjustments in serial kidney biopsies in switch patients. METHODS: All treatment-naïve patients with classical Fabry disease in our centre started on agalsidase-β 1.0 mg/kg/eow and subsequently switched to agalsidase-α 0...
May 17, 2016: Nephrology, Dialysis, Transplantation
Ruya Ozelsancak, Bulent Uyar
BACKGROUND: Fabry disease is an X-linked disorder. Due to deficiency of the enzyme a-galactosidase A, neutral glycosphingolipids (primarily globotriaosylceramide) progressively accumulate within lysosomes of cells in various organ systems, resulting in a multi-system disorder, affecting both men and women. Misdiagnosis and delayed diagnosis are common because of the nature of Fabry disease. CASE REPORT: We report a case of Fabry disease with a p.R301X (c.901 C>T) mutation in a 39-year-old man who was being treated for chronic sclerosing glomerulonephritis for 2 years...
2016: American Journal of Case Reports
Shuichi Ito, Masao Ogura, Koichi Kamei, Kentaro Matsuoka, David G Warnock
BACKGROUND: Fabry disease is an X-linked lysosomal disorder caused by decreased activity of α-galactosidase A (GLA). Consequent accumulation of globotriaosylceramide (GL-3) in lysosomes results in damage to a variety of organs, including the kidneys. Enzyme replacement therapy (ERT) is an effective treatment, but whether it should be started before organ damage is evident is a matter of debate. CASE DIAGNOSIS/TREATMENT: A 10-year-old boy who complained of severe sole pain for 3 years had been misdiagnosed with juvenile idiopathic arthritis...
August 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Alberto Ortiz, Ademola Abiose, Daniel G Bichet, Gustavo Cabrera, Joel Charrow, Dominique P Germain, Robert J Hopkin, Ana Jovanovic, Aleš Linhart, Sonia S Maruti, Michael Mauer, João P Oliveira, Manesh R Patel, Juan Politei, Stephen Waldek, Christoph Wanner, Han-Wook Yoo, David G Warnock
BACKGROUND: Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β...
July 2016: Journal of Medical Genetics
Olivier Lidove, Frédéric Barbey, Dominique Joly
Fabry disease, an X-linked lysosomal storage disease, results from α-galactosidase A deficiency. Two different recombinant enzyme treatments (algalsidase alpha agalsidase beta) have been available since 2001 to treat a disease that affects not only men but also women. Enzyme replacement therapy promotes cell clearance of susbtrate, and improves some clinical parameters (heart, kidney damage, pain, quality of life). However, there is no proven efficacy to date on central nervous system lesions, on cardiac morbidity and mortality, nor on renal damage beyond a certain stage (proteinuria>1g/day and/or estimated glomerular filtration rate<60mL/min/1...
April 2016: Néphrologie & Thérapeutique
Michael Beck, Derralynn Hughes, Christoph Kampmann, Sylvain Larroque, Atul Mehta, Guillem Pintos-Morell, Uma Ramaswami, Michael West, Anna Wijatyk, Roberto Giugliani
Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death...
June 2015: Molecular Genetics and Metabolism Reports
Alberto Ortiz, Maria Dolores Sanchez-Niño
No abstract text is available yet for this article.
2015: Drug Design, Development and Therapy
David G Warnock, Christie P Thomas, Bojan Vujkovac, Ruth C Campbell, Joel Charrow, Dawn A Laney, Leslie L Jackson, William R Wilcox, Christoph Wanner
BACKGROUND: Nephropathy is an important feature of classical Fabry disease, which results in alpha-galactosidase A deficiency and cellular globotriaosylceramide accumulation. We report the safety and efficacy of antiproteinuric therapy with ACE inhibitors or angiotensin II receptor blockers (ARBs) in a study of classical Fabry patients receiving recombinant agalsidase-beta therapy. METHODS AND DESIGN: The goal was maintenance of urine protein to creatinine ratio (UPCR) <0...
December 2015: Journal of Medical Genetics
Takahiro Kanai, Takane Ito, Jun Odaka, Takashi Saito, Jun Aoyagi, Hiroyuki Betsui, Takanori Yamagata
UNLABELLED: Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear...
March 2016: European Journal of Pediatrics
Christoph Kampmann, Amandine Perrin, Michael Beck
BACKGROUND: To explore long-term effects of agalsidase alfa on Fabry disease cardiomyopathy in adults. METHODS: Retrospective analysis of prospectively collected data at a single center in Mainz, Germany, revealed that 45 adult patients (21 men, 24 women) had received agalsidase alfa for approximately 10 years. Data were extracted for cardiac and heart failure status, echocardiographic evaluations of cardiac structure and function, and renal function at treatment start and during agalsidase alfa treatment...
2015: Orphanet Journal of Rare Diseases
Christos Paliouras, Georgios Aperis, Foteini Lamprianou, Giorgos Ntetskas, Konstantinos Roufas, Polichronis Alivanis
Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipids, caused by the partial or complete deficiency of the lysosomal enzyme alpha-galactosidase A (a-Gal A). The missense mutation pN215S usually causes a milder form of the disease with isolated cardiac involvement. We report a case of a male Fabry patient with the pN215S mutation and a generalized disease. He suffered a relapse in proteinuria which responded to increased doses of the administered recombinant enzyme. Individualization of enzyme replacement therapy must be considered in selected cases characterized by clinical deterioration...
November 2015: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
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