Impact of long-term elosulfase alfa treatment on clinical and patient-reported outcomes in patients with mucopolysaccharidosis type IVA: results from a Managed Access Agreement in England

Abstract

Background We present baseline characteristics and follow-up data of a Managed Access Agreement (MAA), including patients with mucopolysaccharidosis IVA (MPS IVA) receiving elosulfase alfa enzyme replacement therapy (ERT) in England on a conditional basis. Patients enrolled in the MAA programme are reviewed on an annual basis. Therapy can be continued if patients are compliant, able to tolerate infusions, and meet four out of five pre-defined clinical and patient-reported outcomes (PRO) criteria. Baseline and follow-up clinical and PRO data are presented for all participants who completed ≥ 1 year of assessments in the MAA. Results The analysis included data from 55 patients, including 26 patients previously enrolled in clinical trials and 29 who started ERT after enrolling in the MAA. In patients with both baseline and follow-up data, mean 6-min walk test distance increased from 217 m at baseline to 244 m after a mean follow-up of 4.9 years. Improvement or stabilisation was seen regardless of age at treatment initiation or duration of treatment. Mean forced vital capacity and forced expiratory volume in 1 s were 0.87 L and 0.78 L, respectively at baseline and 1.05 L and 0.88 L after a mean follow-up of 5.5 years. PRO data showed overall improvements over time in Mobility, Self-care, and Caregiver assistance scores of the MPS-Health Assessment Questionnaire, relatively stable quality of life, and some improvements in pain scores. Conclusions The MAA data confirm the effects of elosulfase alfa on clinical and PRO results observed in the clinical trials and provide real-world evidence for long-term stabilisation in these measures, suggesting a positive impact on the natural history of MPS IVA.

Activity of daily living in mucopolysaccharidosis IVA patients: Evaluation of therapeutic efficacy

“…ERT and HSCT increased only “other MPS symptoms” scores in severe patients, which differed from previously reported data (Cleary et al, 2021 ; Hendriksz et al, 2015 , 2018 ; Moisan et al, 2020 ). Previous clinical trials with ERT showed an improvement in mobility using the health assessment questionnaire and endurance in the 6‐minute walk test, similar to the “movement” section in this study (Cleary et al, 2021 ; Hendriksz et al, 2015 , 2018 ; Moisan et al, 2020 ). Severe ERT patients had a numerical increase in “movement” compared to severe untreated patients without statistical significance.…”

“…ERT treatment improved scores in the health assessment questionnaire, specifically the self‐care and mobility sections, of 51 patients with an average age of 14.9 years (range 2–58 years) over 3 years. In the same study, pain severity remained stable over time, and wheelchair status remained unchanged (Cleary et al, 2021 ).…”

“…Enzyme replacement therapy (ERT), elosulfase alfa (trade name Vimizim), was approved by the United States Food and Drug Administration in 2014 (Drug Approval Package: Vimizim (Elosulfase Alfa), 2014 ). Elosulfase alfa doses at 2 mg/kg weekly normalized urinary KS levels, improved endurance using the 6‐minute walk test but not on the 3‐minute stair climb test, and stabilized pulmonary function using forced vital capacity and forced expiratory volume in 1 second over approximately 5 years (Cleary et al, 2021 ; Hendriksz, Burton, et al, 2014 ; Hendriksz et al, 2018 ). However, another long‐term study over 9 years found that pulmonary function still decreased when corrected for age, sex, and height (Wysong et al, 2012 ).…”

“…However, another long‐term study over 9 years found that pulmonary function still decreased when corrected for age, sex, and height (Wysong et al, 2012 ). As measured using left ventricular ejection fraction, cardiovascular functioning did not change in one study with a mean follow‐up of 4.9 years (Cleary et al, 2021 ). Cardiac hypertrophy stabilized and improved more in younger patients, but valvular heart disease only stabilized over 3–6 years on ERT (Lin et al, 2018 ).…”

The Landscape of Mucopolysaccharidosis in Southern and Eastern European Countries: A Survey from 19 Specialistic Centers.

“…Elosulfase alfa was also shown to improve endurance scores in patients treated for 24 weeks, as measured by the 6 minutes' walk test (6MWT) [20]. Improvement in endurance were also con rmed in a long-term study, up to 4.9 years, both in children and adults [21]. The latter study also showed positive results on clinical and patient-reported outcomes, such as pulmonary function measures and activities of daily living (ADL).…”