Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double‐blind, pilot study

Abstract

The primary treatment outcomes of a phase 2, randomized, double‐blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6‐min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3‐min stair climb test [3MSCT]), exercise capacity (cardio‐pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty‐five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0–4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain. © 2015 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)

“…Notably, mean baseline walking distance was 372 meters, which was considerably more than the Safety results were similar for both doses and were in line with what was previously reported in the primary study [38]. All drug-related AEs were mild to moderate in severity.…”

“…Levels of uKS decreased considerably from baseline after treatment in both dose groups, reaching similar mean and median absolute levels [38]. However, no meaningful changes from baseline in 6MWT distance were observed in either dose group.…”

“…Morquio A [38]. In addition, this is the first report to comprehensively explore aspects of exercise capacity, muscle strength, and pain in patients with Morquio A, providing new insights into the physiology and symptomatology of this disease.…”

“…An additional pilot study evaluated a higher dose of elosulfase alfa in the Morquio A population ≥7 years of age and able to walk ≥200 meters in the 6MWT [38]. These inclusion criteria were selected in order to enroll a population of subjects who were able to perform a cardio-pulmonary exercise test of sufficient duration to provide useful information on cardio-pulmonary/exercise capacity.…”

“…In a randomized, double-blind, uncontrolled pilot study, patients with Morquio A able to walk ≥200 meters in the 6MWT were given 1 of 2 doses of elosulfase alfa-2.0 mg/kg/week or a higher dose of 4.0 mg/kg/week [38]. The study evaluated the effects of the 2 doses on 6MWT, 3MSCT, pharmacokinetic parameters, and uKS levels.…”