001) from 12.15 to 2.0 μg/mL (normal range: < 2.0 to 6.6 μg/mL) and GM3 decreased by 74% from 19.4 to 5.9 μg/mL (normal range: 5.0 to 9.2 μg/mL). Bone pathology represents a primary and often this website progressive clinical

feature of GD1, perhaps caused by a disruption of the normal bone remodeling process [10] and [11]. Long-term eliglustat treatment maintained improvements in both osseous and marrow bone compartments. Fifteen of 19 patients had evaluable bone data over the 4‐year period, 12 of whom had osteopenia or osteoporosis of the lumbar spine at baseline. With eliglustat treatment, the mean bone mineral density (BMD) T-score for the lumbar spine increased significantly (P = 0.014) by 0.8 (9.9% in BMD g/cm2) from baseline see more to 4 years, an improvement that moved the mean T-score out of the osteopenia range (− 1.0 to − 2.5) and into the normal

range (− 1.0 to 1.0) ( Fig. 3). Femur MRI results showed stabilized or improved bone disease over 4 years. Dark marrow, which was present in 18 of 19 (95%) patients at baseline, improved in 9 patients (50%), was stable in 8 patients (44%), and was possibly enlarged in 1 patient (6%) at 4 years [12]. Lytic lesions present in 8 of 19 (42%) patients at baseline remained stable and no new lesions were identified. No bone crises were reported for the duration of the trial. Safety outcomes for the first 2 years of eliglustat treatment have been published [4] and [5]. No substantial new safety issues have arisen since then. After 4 years, a total

of 191 treatment-emergent adverse events were reported in 23 patients, of which 74% were classified as mild and 95% were assessed as unrelated to treatment. Ten related treatment-emergent adverse events, all of which were mild, were reported in eight patients; each related adverse event occurred in one or two patients. All three patients who had peripheral nerve treatment emergent adverse events considered related to treatment were asymptomatic and had discordant neurological exam and nerve conduction findings; all have continued eliglustat treatment [5]. Most related treatment-emergent adverse events (7/10) occurred PARP inhibitor during the first 74 days of treatment. Over 4 years, five serious treatment-emergent adverse events were reported in three patients, all during the first year of treatment and as previously reported. No deaths occurred. In 4 years, there were seven discontinuations; four in the first year (two due to pregnancy and two due to asymptomatic nonsustained ventricular tachycardia after one dose) [4] and [5], two during the second year (pregnancy and bone lesion) [4] and [5], and one during the third year (administrative). Long-term follow-up of eliglustat treatment for previously untreated GD1 patients demonstrated continuation and maintenance of improvements in hematologic parameters, organ volumes, disease-related biomarkers, and bone parameters.