Dataset Information

Elosulfase alfa in the treatment of mucopolysaccharidosis type IVA: insights from the first managed access agreement.

ABSTRACT: Managed access agreements provide a crucial mechanism whereby real-world data can be collected systematically to reduce uncertainty around available clinical and economic data, whilst providing the opportunity to identify patient sub-populations who are most likely to benefit from a new treatment. This manuscript aims to share learnings from the first managed access agreement, which was initiated following positive conditional approval in 2015 from the National Institute for Health and Care Excellence (NICE) for elosulfase alfa, an enzyme replacement therapy for the treatment of mucopolysaccharidosis type IVA (MPS IVA). This managed access agreement enabled the collection of comprehensive real-world data for patients with MPS IVA, with results demonstrating that patients starting elosulfase alfa treatment showed gains similar to those seen in the pivotal trial for outcomes including endurance, respiratory and cardiac function, pain, quality of life measures and urinary keratan sulfate levels. In addition, former trial patients continued to see benefits in both clinical assessments and quality of life/activities of daily living nine years after beginning treatment. Key strengths of the process included recruitment of a high proportion of MPS IVA patients treated in England (72/89 known eligible patients) with a wide range of ages (2-58 years). Participation of a patient organisation (the MPS society) ensured that the patient voice was present throughout the process, whilst a contract research organisation (Rare Disease Research Partners) ensured that patients were represented when interpreting agreement criteria and during patient assessment meetings. Longer-term follow-up will be required for several MPS IVA outcomes (e.g. skeletal measures) to further reduce uncertainty, and continued follow-up of patients who had stopped treatment was found to be challenging. The burden associated with this managed access agreement was found to be high for patients, physicians, patient organisations, NHS England and the manufacturer, therefore costs and benefits of future agreements should be considered carefully before initiation. Through evaluation of the strengths and limitations of this process, it is hoped that learnings from this managed access agreement can be used to inform future agreements.

SUBMITTER: Stevens B

PROVIDER: S-EPMC8467187 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Cardiovascular disease (CVD) in Mucopolysaccharidosis Type IVA (Morquio A), signified by valvular disease and cardiac hypertrophy, is the second leading cause of death and remains untouched by current therapies. Enzyme replacement therapy (ERT) is the gold-standard treatment for MPS disorders including Morquio A. Early administration of ERT improves outcomes of patients from childhood to adulthood while posing new challenges including prognosis of CVD and ERT's negligible effect on cardiovascular health. Thus, having accurate biomarkers for CVD could be critical. Here we show that cathepsin S (CTSS) and elastin (ELN) can be used as biomarkers of extracellular matrix remodeling in Morquio A disease. We found in a cohort of 54 treatment naïve Morquio A patients and 74 normal controls that CTSS shows promising attributes as a biomarker in young Morquio A children. On the other hand, ELN shows promising attributes as a biomarker in adolescent and adult Morquio A. Plasma/urine keratan sulfate (KS), and urinary glycosaminoglycan (GAG) levels were significantly higher in Morquio A patients (p < 0.001) which decreased with age of patients. CTSS levels did not correlate with patients' phenotypic severity but differed significantly between patients (median range 5.45-8.52 ng/mL) and normal controls (median range 9.61-15.9 ng/mL; p < 0.001). We also studied α -2-macroglobulin (A2M), C-reactive protein (CRP), and circulating vascular cell adhesion molecule-1 (sVCAM-1) in a subset of samples to understand the relation between ECM biomarkers and the severity of CVD in Morquio A patients. Our experiments revealed that CRP and sVCAM-1 levels were lower in Morquio A patients compared to normal controls. We also observed a strong inverse correlation between urine/plasma KS and CRP (p = 0.013 and p = 0.022, respectively) in Morquio A patients as well as a moderate correlation between sVCAM-1 and CTSS in Morquio A patients at all ages (p = 0.03). As the first study to date investigating CTSS and ELN levels in Morquio A patients and in the normal population, our results establish a starting point for more elaborate studies in larger populations to understand how CTSS and ELN levels correlate with Morquio A severity.

Dataset Information

Elosulfase alfa in the treatment of mucopolysaccharidosis type IVA: insights from the first managed access agreement.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets