Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study

Eliglustat tartrate is an investigational oral substrate reduction therapy for Gaucher disease type 1 that is pharmacologically distinct from intravenous enzyme replacement therapy. Eliglustat tartrate improved clinical manifestations in patients who received 50 or 100 mg twice daily for 1 year during an open-label phase 2 study (Blood. 2010;116(6):893-899). We report further improvements after 2 years of treatment in 20 patients (11 females, 9 males; mean age, 33 years) with baseline splenomegaly and thrombocytopenia and/or anemia. Statistically significant (P < .001) percentage improvements from baseline occurred in platelet count (mean ± SD, 81% ± 56%), hemoglobin level (20% ± 15%), spleen volume (−52% ± 11%), and liver volume (−24% ± 13%). Mean platelet count increased ∼ 50 000/mm3. Mean hemoglobin level increased 2.1 g/dL overall and 3.1 g/dL in 10 patients with baseline anemia. Organ volume reductions were greatest in patients with severe baseline organomegaly. Seventeen (85%) patients met established therapeutic goals for ≥ 3 of the 4 parameters. Lumbar spine bone mineral density increased 7.8% ± 10.6% (P = .01) and T-score 0.6 ± 0.8 (P = .012), with major gains in osteoporotic and osteopenic patients. Magnetic resonance imaging assessment showed that bone marrow infiltration by Gaucher cells was decreased (8/18 patients) or stable (10/18 patients). No safety-related trends emerged during 2 years of treatment. This multisite, open-label, single-arm phase 2 study is registered at www.clinicaltrials.gov as NCT00358150

FAIR Vocabularies in Population Research: report of the IUSSP-CODATA Working Group on FAIR Vocabularies

This report describes the role of controlled vocabulariesin the documentation and dissemination of demographicdata in the light of the FAIR principles that all datashould be “Findable, Accessible, Interoperable, andReusable” by both humans and machines (Wilkinson etal., 2016). Population research is an empirically focusedfield with a long tradition of widely shared, easilyaccessible, data collections. The FAIR Principles pointto ways that this tradition can be enhanced by takingadvantage of emerging standards and technologies.Our work builds on the “Ten Simple Rules for makinga vocabulary FAIR” (Cox et al., 2021), prepared by agroup formed at a workshop convened by CODATA andDDI to describe how a FAIR vocabulary will work withinternational standards for documenting and sharingsocial science data.Controlled vocabularies play a central role in datasharing by associating data with concepts and bydefining which categories or codes may be applied.FAIR vocabularies specify globally accessible persistentidentifiers to distinguish data items that are the samefrom those that are different. Consider the most basicvariable in demographic analysis: age. The Organizationfor Economic Cooperation and Development (OECD)has a list of 643 age categories, while the UN PopulationDivision copes with more than 1100 age groups. If themeanings of variables in a dataset are only availablethrough human-readable documentation, like a pdf,harmonizing data from two providers will remain atedious manual process. However, if the age categoriesare linked to persistent identifiers in machine actionablemetadata, software can be programmed to harmonizeage groupings. If these operations are performedacross dozens of variables in hundreds of data sources,enormous amounts of human time will be saved.Construction of the infrastructure for FAIR data hasbegun. Demographic concepts are already includedin vocabularies developed by other disciplines, likemedicine, with definitions that conflict with usage inpopulation research. Therefore, there is a need fora FAIR vocabulary of demographic conceptsendorsed by an authoritative institution in thefield of population science.IUSSP has a long history of working with the UNand other agencies to define demographic concepts(International Union for the Scientific Study ofPopulation, 1954; Vincent, 1953). Those efforts currentlyexist in electronic forms (Demopædia and Demovoc)that provide a base for a multilingual FAIR Vocabularyof Demography. We argue that a FAIR Vocabularyof Demography will have important benefits for thepopulation research community represented by IUSSP,and we conclude with recommendations for IUSSP andother important organizations.In addition to summarizing the activities of the WorkingGroup, this report is intended to serve as an introductionto the standards and infrastructure used to share socialscience data. Most demographers have never heard ofURIs, SDMX, or DDI, even though they use servicesfrom the UN, ILO, OECD, CESSDA, IPUMS, andother organizations that depend on these standards.Understanding key features of the international datainfrastructure will help IUSSP leadership to influenceits development

A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1

Eliglustat tartrate (Genz-112638), a specific inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1). A multinational, open-label, single-arm phase 2 study of 26 GD1 patients (16 female, 10 male; mean age, 34 years) evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. Entry criteria required splenomegaly with thrombocytopenia and/or anemia. The composite primary efficacy end point required improvement after 52 weeks in at least 2 of these 3 disease manifestations and was met by 77% (95% confidence interval [CI] = 58%-89%) of all patients and 91% (95% CI = 72%-98%) of the 22 patients completing 52 weeks. Statistically significant improvements occurred in mean hemoglobin level (1.62 g/dL; 95% CI =1.05-2.18 g/dL), platelet count (40.3%; 95% CI = 23.7-57.0 g/dL), spleen volume (−38.5%; 95% CI = −43.5%-−33.5%), liver volume (−17.0%; 95% CI = −21.6%-12.3%), and lumbar spine bone mineral density (0.31 Z-score; 95% CI = 0.09-0.53). Elevated biomarkers (chitotriosidase; chemokine CCL18; angiotensin-converting enzyme; tartrate-resistant acid phosphatase) decreased by 35% to 50%. Plasma glucosylceramide and ganglioside GM3 normalized. Eliglustat tartrate was well tolerated: 7 mild, transient adverse events in 6 patients were considered treatment-related. Individual pharmacokinetics varied; mean time to maximal observed concentration was 2.3 hours and mean half-life was 6.8 hours. Eliglustat tartrate appears to be a promising oral treatment for GD1. This study is registered at www.clinicaltrials.gov as #NCT00358150