Long-term outcomes of elosulfase alfa enzyme replacement therapy in adults with MPS IVA: a sub-analysis of the Morquio A Registry Study (MARS)

TL;DR

This study examines the long-term effects of enzyme replacement therapy in adults with a rare genetic disorder called Morquio A syndrome, finding that treatment is safe and stabilizes key health measures over seven years.

Contribution

The study provides real-world, long-term safety and effectiveness data for elosulfase alfa in adult Morquio A syndrome patients, over seven years of follow-up.

Findings

Elosulfase alfa therapy led to sustained reductions in urinary keratan sulfate levels over a mean follow-up of 5.4 years.

Lung function (FEV1 and FVC) remained stable over a mean follow-up of 5.3 years.

No new safety signals were identified, with most adverse events being non-serious and unrelated to the drug.

Abstract

Mucopolysaccharidosis (MPS) IVA is a rare disease with substantial, multisystemic morbidity. We assessed real-world safety and effectiveness of the enzyme replacement therapy (ERT) elosulfase alfa in patients with MPS IVA in the multinational, observational Morquio A Registry Study (MARS) who initiated ERT in adulthood (aged ≥ 18 years).

Patients were enrolled between September 2014 and February 2022; urinary keratan sulfate (uKS), 6-minute walk test (6MWT) distance, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), EuroQoL-5D-5L (EQ-5D-5L) score, and safety were assessed during routine care.

As of February 13, 2022, 90 patients who initiated ERT had enrolled (median exposure: 5.6 years; median age at first ERT: 27.8 years). Reductions from baseline in uKS levels were sustained over mean follow-up of 5.4 years (mean percent change: -52.9%; p < 0.0001). In patients with available data, mean change in 6MWT distance was + 15.8 m (p = 0.3627) over a mean follow-up of 5.8 years. FEV1 and FVC remained stable over mean follow-up of 5.3 years (mean change: 0.0 L for both). The mean change from baseline in EQ-5D-5L index score was + 0.1 after 1 year of treatment. Thirty-four patients (39.5%) had ≥ 1 adverse event (AE), 23 patients (26.7%) had ≥ 1 serious AE, and 10 (11.6%) had ≥ 1 drug-related AE (infusion-related reactions [n = 3; 3.5%], pyrexia [n = 2; 2.3%]). Eight deaths occurred; none were deemed treatment related.

Real-world data collected from MARS suggest that patients with MPS IVA who initiated ERT in adulthood remained stable over 7 years of follow-up. No new safety signals were identified.

The online version contains supplementary material available at 10.1186/s13023-025-04064-w.

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