Velaglucerase alfa for treatment in children with Gaucher disease type 1: the Russian experience

The current gold standard for the treatment of Gaucher disease type 1 in children is enzyme replacement therapy. The efficacy and safety of treatment with velaglucerase alfa have been assessed in only a few large studies involving pediatric patients as subjects of research. In the Russian literature, there are no data available on the use of velaglucerase alfa in drug-naïve patients with Gaucher disease type 1. The aim of our study was to assess the efficacy and safety of treatment with velaglucerase alfa in children with Gaucher disease type 1. The study was approved by the Independent Ethics Committee and the Scientific Council of the National Medical Research Center for Children's Health of Ministry of Healthcare of the Russian Federation. All patients and/or their legal representatives gave their informed consent to the study. The efficacy of treatment with velaglucerase alfa in children with Gaucher disease type 1 was assessed by analyzing monitoring data of 15 patients aged 2 to 15 years who had been registered in the Russian Pediatric Gaucher Registry established at National Medical Research Center for Children's Health of Ministry of Healthcare of Russia over the period from 2015 to 2023. None of the patients had ever undergone enzyme replacement therapy before they were included in this study. The median age at the start of treatment was 6.5 years. We analyzed the patients' anthropometric, laboratory and instrumental data at 0, 6, 12, 24 and 36 months. The initial dose of enzyme replacement therapy ranged from 30 to 60 units/kg (with the median of 43 units/kg per infusion) once every 2 weeks based on disease severity. In as little as 6 months after the initiation of therapy with velaglucerase alfa, patients with Gaucher disease type 1 showed a statistically significant improvement in all measured parameters (p < 0.001): normalization of the median hemoglobin concentration and platelet count (from 113 to 125 g/L and from 111 to 163 × 109/L, respectively); a reduction in degree of liver and spleen enlargement (in terms of volume, from 45.1 to 17.9% and from 39.4 to 15.5%, respectively); a reduction in degree of the right liver lobe enlargement (in terms of linear measurements, from 27.2 to 11.1%); a reduction in degree of spleen enlargement (in terms of its length and width, from 73.4 to 37.8% and from 60.3 to 17.5%, respectively). Our patients had a remarkable decrease in biomarker activity after 3 years of therapy: chitotriosidase activity decreased from 2699 to 227 nmol/mL/h and glucosylsphingosine level was reduced from 204.0 to 35.3 ng/mL (р < 0.001). There were no adverse events during the course of treatment. After 6 months and 1 year of regular enzyme replacement therapy with appropriate doses of velaglucerase alfa initiated in a timely manner, children with Gaucher disease type 1 achieve normal hemoglobin concentrations and platelet counts, a reduction in biomarker activity, and a decrease in liver and spleen volumes. After 3 years of enzyme replacement therapy, patients achieve their main therapeutic goals such as the resolution of anemia and thrombocytopenia, an almost complete regression of hepatosplenomegaly and the normalization of bone mineral density and height adjusted for age.