Sonila Tomori

Background/Objectives: Gaucher disease type 1 is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the GBA1 gene. Although enzyme replacement therapy has improved patient outcomes, there is limited long-term real-world data on taliglucerase alfa. This study aimed to evaluate the long-term efficacy and safety of taliglucerase alfa in both treatment-naïve and previously treated patients with Gaucher disease type 1 over a 10-year period. Methods: This prospective, single-centre cohort study involved 29 patients (13 treatment-naïve and 16 previously treated with imiglucerase) who received taliglucerase alfa from 2015 to 2024. Clinical, hematological, visceral, skeletal, and biochemical parameters were assessed at baseline and at 12, 60, and 120 months. Biomarkers included chitotriosidase and glucosylsphingosine. Safety was evaluated through adverse event reporting and anti-drug antibody testing. Results: Hemoglobin and platelet counts improved or remained stable in all patients. By 60 months, liver volume had normalised in treatment-naïve patients (mean reduction: 23.1%), while spleen volume had decreased by up to 47.3%. Lyso-Gb1 levels decreased by 86.1% in patients who had not previously received treatment and by 59.5% overall, with a strong correlation to adherence. Bone mineral density improved in most cases. 137 adverse events were reported, 24% of which were mild infusion-related reactions. Anti-drug antibody developed in two patients, including one with a reduced therapeutic response. Conclusions: Taliglucerase alfa offers sustained long-term clinical, hematological and biochemical benefits in both treatment-naïve and previously treated Gaucher disease type 1 patients, with a favorable safety profile. Glucosylsphingosine proved to be a highly sensitive biomarker for monitoring therapeutic efficacy and detecting treatment response.

Gaucher disease (GD) is a lysosomal storage disorder that responds well to enzyme replacement therapy (ERT). Certain laboratory parameters, including blood concentration of glucosylsphingosine (Lyso-Gb1), the lyso-derivate of the common glycolipid glucocerebroside, correlate with clinical improvement and are therefore considered candidate-monitoring biomarkers. Whether they can indicate a reduction or loss of treatment efficiency, however, has not been systematically addressed for obvious reasons. We established and validated measurement of Lyso-Gb1 from dried blood spots (DBSs) by mass spectrometry. We then characterized the assay’s longitudinal performance in 19 stably ERT-treated GD patients by dense monitoring over a 3-year period. The observed level of fluctuation was accounted for in the subsequent development of a unifying data normalization concept. The resulting approach was eventually applied to data from Lyso-Gb1 measurements after an involuntary treatment break for all 19 patients. It enabled separation of the “under treatment” versus “not under treatment” conditions with high sensitivity and specificity. We conclude that Lyso-Gb1 determination from DBSs indicates treatment issues already at an early stage before clinical consequences arise. In addition to its previously shown diagnostic utility, Lyso-Gb1 thereby qualifies as a monitoring biomarker in GD patients.