Effects of oral eliglustat on skeletal manifestations in patients with type 1 Gaucher disease: Results from four completed clinical trials after long-term treatment

Debilitating bone complications are common among patients with Gaucher disease type 1 (GD1). We analyzed changes in bone parameters among 393 GD1 patients treated with oral eliglustat for 4–8 years in 4 Sanofi Genzyme-sponsored clinical trials (Phase 2/NCT00358150 [N=26]; Phase 3: ENGAGE/NCT00891202 [N=40]; ENCORE/NCT00943111 [N=157]; EDGE/NCT01074944 [N=170]. In treatment-naïve patients (Phase 2/ ENGAGE), mean spine T-scores moved from the osteopenic range at baseline to the healthy range after 2–3 years. Mean±SEM spine T score increased from 1.55±0.28 to 0.59±0.34 (n=14) after 8 years in Phase 2, and increased to 0.53±0.27 in ENGAGE after 4.5 years (n=9). In both trials, spine Z-scores improved and femur T- and Z-scores remained normal. In ENCORE (patients stabilized after a mean of 10 years of enzyme replacement therapy [ERT]), T- and Z-scores remained in reference ranges for up to 4 years; least-square mean spine Z-scores improved by 0.29 (P<0.0001). In EDGE (mostly ERT switch), patients stabilized during the Lead-In maintained normal T- and Z-scores through the dose-regimen arm and extension period. Mean total bone marrow burden scores improved from marked-to-severe to moderate in ENGAGE and remained stable (moderate) throughout ENCORE and EDGE. Proportions of patients experiencing bone pain decreased after treatment in all trials; reported pain became less severe. Bone crises were infrequent, with none in Phase 2 or ENGAGE patients and in 3/157 (1.9%) patients in ENCORE and 6/170 (3.5%) in EDGE (3 of whom had bone crises before trial entry). Median macrophage inflammatory protein-1β levels normalized in ENGAGE and remained normal in ENCORE and EDGE. Eliglustat was generally well-tolerated. Overall, 97% of adverse events were mild/moderate (97%) and 86% considered unrelated to eliglustat; 9 (2.3% overall) patients withdrew due to adverse events considered drug-related. In summary, bone-related parameters showed improvement in treatment-naïve patients and stability or improvement in switch patients.Sanofi Genzym

HEALTH CARE POLICY IN THE GERMAN SOCIAL INSURANCE STATE: From Solidarity to Privatization&quest;

Statutory health insurance is a centerpiece of the German welfare state, which considers itself to be a "social insurance state." At the same time, due to a large volume of interpersonal redistributions that occur in health insurance, it is the most ambitious branch of the country's social insurance system. The stability of the health scheme thus depends on a "culture of solidarity" to maintain the legitimacy of these redistributions. This article analyzes recent changes in the legislative framework of the statutory health insurance. It asks whether these changes which predominantly aim to contain employers' nonwage labor costs by making the insured bear a larger share of total health care spending, are possibly weakening the moral infrastructure of the welfare state. To this end, findings from qualitative interviews with insured persons are evaluated in view of recently approved and currently proposed legislative changes to the health scheme. The analytical focus is the question whether the two equity principles of this scheme, delivering health care according to medical need and financing it according to the "ability-to-pay," are becoming endangered. Copyright 2002 by The Policy Studies Organization.