Cox Timothy M, Drelichman Guillermo, Cravo Renata, Balwani Manisha, Burrow Thomas Andrew, Martins Ana Maria, Lukina Elena, Rosenbloom Barry, Goker-Alpan Ozlem, Watman Nora, El-Beshlawy Amal, Kishnani Priya S, Pedroso Maria Lucia, Gaemers Sebastiaan J M, Tayag Regina, Peterschmitt M Judith
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Blood. 2017 Apr 27;129(17):2375-2383. doi: 10.1182/blood-2016-12-758409. Epub 2017 Feb 6.
In the phase 3 Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE), at 1 year, eliglustat was noninferior to imiglucerase enzyme therapy in maintaining stable platelet counts, hemoglobin concentrations, and spleen and liver volumes. After this primary analysis period, patients entered a long-term extension phase in which all received eliglustat. Duration on eliglustat ranged from 2 to 5 years, depending on timing of enrollment (which spanned 2 years), treatment group to which patients were randomized, and whether they lived in the United States when commercial eliglustat became available. Here we report long-term safety and efficacy of eliglustat for 157 patients who received eliglustat in the ENCORE trial; data are available for 46 patients who received eliglustat for 4 years. Mean hemoglobin concentration, platelet count, and spleen and liver volumes remained stable for up to 4 years. Year to year, all 4 measures remained collectively stable (composite end point relative to baseline values) in ≥85% of patients as well as individually in ≥92%. Mean bone mineral density z scores (lumbar spine and femur) remained stable and were maintained in the healthy reference range throughout. Eliglustat was well tolerated over 4 years; 4 (2.5%) patients withdrew because of adverse events that were considered related to the study drug. No new or long-term safety concerns were identified. Clinical stability assessed by composite and individual measures was maintained in adults with Gaucher disease type 1 treated with eliglustat who remained in the ENCORE trial for up to 4 years. This trial was registered at www.clinicaltrials.gov as #NCT00943111.
在一项关于酒石酸 eliglustat(Genz-112638)用于已通过酶替代疗法达到治疗目标的戈谢病患者的 3 期研究(ENCORE)中,在 1 年时,eliglustat 在维持稳定的血小板计数、血红蛋白浓度以及脾脏和肝脏体积方面不劣于伊米苷酶疗法。在这个主要分析期之后,患者进入长期延长期,在此期间所有患者均接受 eliglustat 治疗。eliglustat 的治疗时长为 2 至 5 年,具体取决于入组时间(跨度为 2 年)、患者随机分配的治疗组以及在 eliglustat 上市时他们是否居住在美国。在此,我们报告了在 ENCORE 试验中接受 eliglustat 治疗的 157 例患者的长期安全性和疗效;现有 46 例接受 eliglustat 治疗 4 年患者的数据。平均血红蛋白浓度、血小板计数以及脾脏和肝脏体积在长达 4 年的时间里保持稳定。逐年来看,所有这 4 项指标在≥85%的患者中总体保持稳定(相对于基线值的复合终点),且在≥92%的患者中个体指标保持稳定。平均骨矿物质密度 z 评分(腰椎和股骨)保持稳定,并始终维持在健康参考范围内。eliglustat 在 4 年期间耐受性良好;4 例(2.5%)患者因被认为与研究药物相关的不良事件而退出。未发现新的或长期的安全问题。对于在 ENCORE 试验中接受 eliglustat 治疗长达 4 年的 1 型戈谢病成年患者,通过复合指标和个体指标评估的临床稳定性得以维持。该试验已在 www.clinicaltrials.gov 上注册,注册号为 #NCT00943111。