Velaglucerase alfa 400units powder for solution for infusion vials

Gaucher disease (GD) is a rare autosomal recessive genetic disorder. The clinical manifestations can be adequately managed with enzyme replacement therapy (ERT). The aim of this systematic literature review was to explore the safety and efficacy or effectiveness (depending on the type of evidence) profile of velaglucerase alfa in the treatment of paediatric patients with type 1 (GD1) and type 3 (GD3) GD across all paediatric ages. A systematic review of the PubMed/Medline and Embase databases, along with communications from international conferences, was conducted. The inclusion criteria comprised clinical studies published in either English or Spanish that assessed the therapeutic profile of velaglucerase alfa in patients with GD1 (primarily) and GD3 (exploratorily) of all paediatric ages (0–18 years). For each of the selected publications, data regarding the safety and efficacy/effectiveness of this treatment were extracted. A total of 539 publications were identified, of which 23 studies encompassing data from 159 paediatric patients were included. Nine studies (71 patients) provided information about the safety in paediatric patients with GD1, describing it as well tolerated. Regarding the efficacy/effectiveness, 14 articles (113 patients) reported relevant data for the same subpopulation. Overall, improvements in haematological, visceral, skeletal, biomarker and health-related quality-of-life outcomes have been described in treatment-naïve paediatric patients with GD1 who were initially treated with velaglucerase alfa, as well as maintained stability in patients previously treated with imiglucerase. Furthermore, it has been reported that the safety and efficacy/effectiveness profile administered as home therapy enhances the quality of life for both patients and caregivers. The use of velaglucerase alfa in paediatric patients with GD3 was described in 7 publications (26 patients), suggesting a favourable safety profile, whereas its efficacy/effectiveness was reported in 5 articles (16 patients). Improvements in the non-neurological manifestations of the disease were recorded in patients with GD3. This systematic review summarizes the limited evidence on velaglucerase alfa in paediatric patients with GD. Findings suggest that velaglucerase alfa may be a beneficial option for GD1 across all paediatric age groups (0–18 years). Additionally, it might be considered a therapeutic option for non-neurological GD3 symptoms, although evidence is scarce and exploratory, highlighting the need for further research in those patients.

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BACKGROUND: Enzyme replacement therapy (ERT) has revolutionised the management of patients with Gaucher disease (GD). In 2018, we published the safety and efficacy of rapid 10-min infusion of velaglucerase alfa in previously treated patients, mostly on low-dose therapy. AIM: To improve quality of life (QoL) for patients needing lifelong bi-weekly infusions by introducing a 10-min infusion instead of 1 h per label in patients naive to ERT and on high-dose therapy. METHODS: Fifteen naive patients were enrolled; all received bi-weekly infusions of 60 units/kgBW velaglucerase alfa; the infusion rate was gradually reduced in the hospital, followed by home infusions. Each infusion was followed for safety. Efficacy parameters were assessed every 3 months. Patient-reported outcome questionnaires were collected at baseline and follow-up. RESULTS: Ten-minute rapid infusions were well tolerated without related severe adverse events (SAEs). Two patients experienced a non-related SAE and another a possibly related AE. In three patients, the infusion rate was increased to 30 or 60 min (two because of suboptimal response and one because of AE). Two patients dropped out because of an unwillingness to attend follow-up visits during the COVID-19 pandemic. All 13 remaining patients reached the 24-month end-point. The platelet counts increased by a median (range) of 68.38% (12.5-300%) and the lyso-Gb1 levels decreased by 62.6% (32.9-89.9%). CONCLUSION: Home therapy with rapid infusion of high-dose velaglucerase alfa was a safe, effective and preferable alternative for patients with GD naïve to treatment. We believe that shortening the infusion time improves the QoL of patients with GD who have a lifelong commitment to intravenous therapy.

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Background: Gaucher disease (GD) is a rare, autosomal, recessive condition characterized by hepatosplenomegaly, thrombocytopenia, anemia, and bone abnormalities, often requiring life-long treatment. Velaglucerase alfa has improved hematologic and visceral parameters in clinical trials; however, limited long-term efficacy and safety data are available. Methods: The Gaucher Outcome Survey (GOS), a structured and validated international registry for patients with confirmed GD, provides an opportunity to evaluate long-term data from patients receiving velaglucerase alfa. Results: This analysis included 376 treatment-naïve children and adults with GD enrolled in GOS, including 20 with type 3 GD, who initiated velaglucerase alfa through participation in clinical trials or as part of their clinical management and continued treatment for a mean (range) time of 6.6 (0.003–18.6) years. Initial improvements in hematologic and visceral parameters and the biomarkers glucosylsphingosine (lyso-GL1) and chitotriosidase were observed after one year of treatment and were maintained throughout the follow-up period. Of 129 (34.3%) patients who developed adverse events during the follow-up period, events were considered related to treatment in 33 (8.8%). None led to treatment discontinuation. There were 21 deaths overall, none of which were considered related to treatment. Conclusions: This analysis of data from the GOS registry supports the safety and efficacy of velaglucerase alfa in patients with GD.

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Background/Objectives: Gaucher disease type 1 (GD1) is characterized by hepatosplenomegaly, thrombocytopenia, and disabling bone manifestations requiring regular MRI monitoring. The EIROS study assessed the real-world impact of velaglucerase alfa on GD1 bone disease, using MRI data collected in French clinical practice. Methods: MRIs collected retrospectively from treatment initiation and prospectively during follow-up (12-months) were analyzed centrally by a blinded expert radiologist to evaluate bone infiltration using the Bone Marrow Burden (BMB) score and a qualitative method (stable, improved or worsened for the spine and femur). Abdominal MRIs were also centrally analyzed to assess hepatosplenomegaly. Bone manifestations, hepatosplenomegaly, and hematologic parameters were analyzed from medical records. Results: MRI data were available for 20 patients: 6 treatment-naive patients and 14 patients who switched to velaglucerase alfa from another GD treatment. Interpretable MRIs for BMB scoring were available for seven patients for the spine and one patient for the femur. Qualitative assessments (n = 18) revealed stability in spine and femur infiltration in 100.0% and 84.6% of treatment-switched patients (n = 13), respectively, and improvements in 80.0% and 60.0% of treatment-naive patients (n = 5), respectively; no worsening of bone infiltration was observed. Liver, spleen, and hematologic parameters improved in treatment-naive patients and remained stable in treatment-switched patients. Conclusions: The qualitative real-world data support findings from clinical trials suggesting the long-term effectiveness of velaglucerase alfa on GD1 bone manifestations. When MRI assessment by radiologists with experience of GD is not possible, a simplified qualitative assessment may be sufficient in clinical practice for monitoring bone disease progression and treatment response.

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Gaucher disease (GD), an autosomal recessive lipid storage disorder, arises from mutations in the GBA1 (β-glucocerebrosidase) gene, resulting in glucosylceramide accumulation in tissue macrophages. Lyso-Gb1 (glucosylsphingosine, lyso-GL1), a downstream metabolic product of glucosylceramide, has been identified as a promising biomarker for the diagnosis and monitoring of patients with GD. This retrospective, exploratory analysis of data from phase 3 clinical trials of velaglucerase alfa in patients with type 1 GD evaluated the potential of lyso-Gb1 as a specific and sensitive biomarker for GD. A total of 22 treatment-naïve patients and 21 patients previously treated with imiglucerase (switch patients) were included in the analysis. Overall, demographics between the two groups were similar. Mean lyso-Gb1 concentrations were reduced by 302.2ng/mL from baseline to week 209 in treatment-naïve patients and by 57.3ng/mL from baseline to week 161 in switch patients, corresponding to relative reductions of 82.7% and 52.0%, respectively. In both the treatment-naïve and switch groups, baseline mean lyso-Gb1 was higher for patients with at least one N370S mutation (363.9ng/mL and 90.7ng/mL, respectively) than for patients with non-N370S mutations (184.6ng/mL and 28.3ng/mL, respectively). Moderate correlations between decreasing lyso-Gb1 levels and increasing platelet counts, and with decreasing spleen volumes, were observed at some time points in the treatment-naïve group but not in the switch group. These findings support the utility of lyso-Gb1 as a sensitive and reliable biomarker for GD, and suggest that quantitation of this biomarker could serve as an indicator of disease burden and response to treatment.

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BACKGROUND: Fabry disease and Gaucher disease are rare genetic disorders characterized by defective degradation of glycosphingolipids caused by enzymatic deficiencies in α-galactosidase A and β-glucocerebrosidase, respectively, and often require life-long treatment. Treatment options for these disorders include replacing the deficient enzymes via enzyme replacement therapy (ERT). Agalsidase alfa for Fabry disease and velaglucerase alfa for Gaucher disease are two ERT options with demonstrated efficacy, safety, and tolerability. ERT infusions administered by a health care provider (HCP) in the clinic/hospital, or at the patient's home are considered HCP-supported infusions. Self-administration of ERT (by patient, partner, relative, or caregiver) is optional in patients who tolerate the HCP-supported infusions at home and have a suitable home environment. This analysis explored the safety profiles of self-administered agalsidase alfa (202 patients) and velaglucerase alfa (30 patients) versus HCP-supported infusions using data from the Fabry Outcome Survey (FOS) and Gaucher Outcome Survey (GOS) registries. RESULTS: The frequency of infusion-related reactions (IRRs) adverse events (AEs) recorded in the two registries was lower in patients self-administering (FOS: 4.5%, GOS: 0%) versus patients receiving HCP-supported infusions (FOS: 13.6%, GOS: 1.6%). In the FOS registry, AE rates per 100 patient-years (100PY) of follow-up were similar between the self-administration (7.99) and HCP-supported infusion (6.78) groups. In patients self-administering agalsidase alfa, cardiac disorders were the most frequently reported AEs (19 [9.4%] patients) and serious AEs (12 [5.9%]) and gastrointestinal disorders were the most frequently reported IRRs (3 [1.5%]). In the GOS registry, AE rates per 100PY were similar between self-administration (4.97) and HCP-supported infusion (4.67) groups. In patients self-administering velaglucerase alfa, skin and subcutaneous disorders (4 [13.3%]) and infections and infestations (2 [6.7%]) were the most reported AEs and serious AEs, respectively, and no IRRs were reported. CONCLUSIONS: These findings suggest that self-administration of agalsidase alfa or velaglucerase alfa infusions are not associated with additional safety risks compared with HCP-supported infusions and are a suitable option for qualifying patients. Further research is warranted to support these findings and to explore further the long-term safety and efficacy of ERT self-administration. FOS trial registration: ClinicalTrials.gov, NCT03289065. Registered 01 April 2001, https://clinicaltrials.gov/study/NCT03289065 . GOS trial registration: ClinicalTrials.gov, NCT03291223. Registered 27 July 2010, https://classic. CLINICALTRIALS: gov/ct2/show/NCT03291223 .

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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.

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