Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open‐label, phase 2 study

Abstract

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open‐label, phase 2, multi‐national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6‐min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25‐foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug‐related adverse events, the other was not drug‐related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Elosulfase alfa (BMN 110) for the treatment of mucopolysaccharidosis IVA (Morquio A Syndrome)

“…Unfortunately, most patients had difficulty performing these tests according to the study protocol due to weak grip, hypermobile wrists, and/or short stature (ie, patients were unable to put their feet on the floor), leading to differences in test execution among centers. Regardless of test execution methods, grip and pinch strength remained unchanged over the course of the study [36].…”

“…The first evaluated patients ≥5 years of age with limited ambulation (unable to walk ≥30 meters in the 6MWT) using a variety of alternative assessments [36]. The second evaluated patients under 5 years of age, focused on safety and tolerability, and utilized uKS and growth velocity as efficacy measures [37].…”

“…Efficacy and safety of elosulfase alfa ERT were assessed in an open-label, phase 2, multinational study in 15 patients with Morquio A older than 5 years of age who were also unable to walk more than 30 m in the 6MWT [36]. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for Upper extremity function was also assessed by grip and pinch strength tests.…”

“…Mean (SE) speed in the T25FW at baseline was 22.9 (10.3) feet/minute [36]. In several cases, the T25FW was not performed either at the discretion of the investigator and/or for patients with significant pain.…”

“…However, benefits to patients are not adequately captured in QOL assessments [36]. In the recently published limited ambulation study, patients with Morquio A showed improvement after treatment with elosulfase alfa in personally significant ways such as with 1 patient who after treatment was able to type on a computer, reach behind her head, and drink from a cup.…”