Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orphan drugs are often approved under exceptional circumstances, requiring submission of additional data on safety and effectiveness through registries. These registries are mainly focused on one drug only and data is frequently incomplete. Some registries also address phenotypic heterogeneity and natural history data and publications on these aspects have contributed to the knowledge and awareness of these rare diseases. However, for the assessment of long-term outcomes and for cost-effectiveness, the incompleteness and variable quality of the data raises concerns on the usefulness of these registries. The existing registries for orphan drug treatments for lysosomal storage disorders (LSD's) illustrate these limitations. LSD's are inherited disorders of lysosomal metabolism with a wide variety in clinical symptoms, ranging from severe life-threatening neurological disease to mild or even asymptomatic cases. Their prevalence is extremely low and thus data is scarce and scattered all over Europe. In the past few years, several enzyme replacement therapies and an oral substrate inhibitor have been developed which provide lifelong treatment of LSD's. For Fabry disease, two enzymes were authorized at the same time resulting in two different drug registries being required by the European Medicines Agency (EMA) to monitor effectiveness and safety. This has lead to patient data being divided between two separate registries which may have contributed to delays in the assessment of important outcomes. Three treatments (including a recently approved new enzyme) have now been authorized for Gaucher Disease and two other potential therapies are in the pipeline. Dividing up the data on Gaucher disease patients in to five separate registries benefits nobody. We argue that disease specific (rather than drug specific) registries, supervised by independent clinicians are urgently needed for the best long-term evaluation of treatments of these rare diseases.
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PMID:Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders. 2149 91

Commercial treatment for a lysosomal storage disorder (LSD; i.e., Gaucher disease) became available in 1991 as a consequence of collaborative efforts between the National Institutes of Health and a biotechnology company, Genzyme Corporation, fostered by the Orphan Drug Act. (ODA, 1983) Other therapies were subsequently introduced for other LSDs (e.g., for Fabry disease) through ODA-driven incentives, as combined projects between academia and industry, facilitated by the Bayh-Dole Act (1980). Today, several enzyme therapies are available and other treatment options are anticipated, including small molecular drugs which inhibit substrate synthesis or act as pharmacologic chaperones. Disease-specific therapies has modified disease course to varying extents, and on-going data collection through registry/observational programs are in place to characterize both long-term safety and efficacy. Aspects of disease that remain challenging include those resulting from bone and brain involvement, which may necessitate novel therapeutic strategies. Issues related to high cost of therapy and access also remain to be addressed.
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PMID:Orphan drug development. 2438 Jan 24