Galsulfase 5mg/5ml solution for infusion vials

INTRODUCTION: Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder, characterized primarily by skeletal dysplasia and joint contracture. It is caused by a deficiency of N-acetylgalactosamine-4-sulfatase (arylsulfatase B), for which a recombinant formulation (galsulfase) is available as replacement therapy. OBJECTIVE: To evaluate the effectiveness and safety of galsulfase compared to placebo or no interventions, for treating MPS VI. We also considered studies evaluating different doses of galsulfase. METHODS: A systematic review of the literature was conducted. A computerized electronic search in MEDLINE, EMBASE, CENTRAL, SciELO, and LILACS was carried on to identify any randomized trials that met our inclusion criteria. RESULTS: Two studies were included in the review. Because the number of studies was small, our analysis probably did not find any statistically significant difference. Long-term follow-up will be required to ascertain full clinical benefit, on both event-free survival and quality of life measures. CONCLUSIONS: There is some evidence to support the use of galsulfase in the treatment of MPS VI; however due to the very low quantity of included studies we could not analyze it in an appropriate way. This review highlights the need for continued research into the use of enzyme replacement therapy for MPS VI.

Abstract licence: CC BY-NC 3.0

BackgroundAssociated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs).ObjectiveAn analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings.MethodsThe FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance.ResultsTwenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72 PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471 days, with over half of the cases occurred within the first 5 years of treatment initiation.ConclusionThis investigation delivers an exhaustive and indicative assessment of galsulfase's safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.

Abstract licence: CC BY 4.0

Introduction Budget impact analyses for the treatment of rare diseases are especially important for the sustainability of health systems due to high treatment costs and uncertainties in target population estimates. The objective of this work is to analyze the elements that influence discrepancies between predicted and observed budget impacts for enzyme replacement therapies for rare diseases in Brazil’s public health system. Methods All enzyme replacement therapies for rare diseases evaluated by the National Committee for Health Technology Incorporation in the Brazilian Public Health System (Conitec) and with at least one year of use were included. For each technology, the following were identified: number of patients, median patient weight, annual quantity of medication, unit price, and budget impact. The attributes were compared between previous estimates and real-world observation after use. The data sources were publicly accessible administrative databases and Conitec technical reports. Results Five technologies were selected: elosulfase alfa, alglucosidase alfa, idursulfase, laronidase, and galsulfase. In the first year, the difference between the estimated and the observed number of patients treated was up to 15 percent lower or higher for four technologies, but with monthly fluctuation throughout the year. The median weight of users was between 23 percent and 468 percent higher for three technologies. The observed price was as expected, with variations between three percent lower and 14 percent higher. The quantity of medicines used was lower (between 39% and 46%) than expected for all technologies. The observed budget impact was 37 percent to 47 percent lower than estimated. Conclusions Real-world budget impact was lower than expected for all technologies. The main cause of discrepancies was the estimate of the annual amount of medication, which did not consider gradual adherence and discontinuation of treatment. This highlights the need to review the budget impact methodology for rare diseases, forecasting monthly market share and treatment discontinuation rate.

Abstract licence: CC BY