Multi-domain impact of elosulfase alfa in Morquio A syndrome in the pivotal phase III trial

Hendriksz, Christian J.; Giugliani, Roberto; Harmatz, Paul; Mengel, Eugen; Guffon, Nathalie; Valayannopoulos, Vassili; Parini, Rossella; Hughes, D.A.; Pastores, Gregory M.; Lau, Heather; AlSayed, Moeenaldeen; Raiman, Julian; Yang, Ke; Mealiffe, Matthew E.; Haller, Christine

doi:10.1016/j.ymgme.2014.08.012

Cited by 67 publications

(86 citation statements)

References 25 publications

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“…ADL, as assessed by the MPS Health Assessment Questionnaire (MPS HAQ), have been measured as an exploratory endpoint in some clinical trials [32, 33], as well as in a number of studies in patients with MPS II, IV and VI [11, 14, 34, 35] (Table 2). Overall difficulties with mobility and self-care, which tend to increase with age, have been reported.…”

Section: Disease Impact On Pros In Mpsmentioning

confidence: 99%

Health-related quality of life in mucopolysaccharidosis: looking beyond biomedical issues

Hendriksz

Berger

Lampe

et al. 2016

Orphanet J Rare Dis

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The mucopolysaccharidoses (MPS) comprise a heterogeneous family of rare, genetic lysosomal storage disorders that result in severe morbidity and reduced life expectancy. Emerging treatments for several of these disorders have triggered the search for clinically relevant biomarkers and clinical markers associated with treatment efficacy in populations and individuals. However, biomedical measures do not tell the whole story when characterizing a complex chronic disorder such as MPS. Health-related quality of life (HRQoL) tools that utilize patient reported outcomes to address patient parameters such as symptoms (pain, fatigue, psychological health), functioning (activity and limitations), or quality of life, have been used to supplement traditional biomedical endpoints. Many of these HRQoL tools have demonstrated that quality of life is negatively impacted in patients with MPS. There is both the opportunity and need to formally standardize and validate HRQoL tools for the different MPS disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0503-2) contains supplementary material, which is available to authorized users.

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Section: Disease Impact On Pros In Mpsmentioning

confidence: 99%

Health-related quality of life in mucopolysaccharidosis: looking beyond biomedical issues

Hendriksz

Berger

Lampe

et al. 2016

Orphanet J Rare Dis

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“…A Phase III 24-week, randomized, double-blind, placebo (PBO)-controlled trial in 176 patients evaluated two dosing regimens: 2 mg/kg/dose weekly (2 mg/kg QW; n = 58) and 2 mg/kg/dose every other week (2 mg/kg QOW; n = 59), compared with PBO ( n = 59) [60,61]. The Phase III trial included patients aged between 5 and 57 years old.…”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

“…Patients treated with ERT showed positive changes in maximal voluntary ventilation, MPS-Health Assessment Questionnaire (MPS-HAQ), and height/growth rate, although these changes were not statistically significant [19,61]. …”

Section: Enzyme Replacement Therapymentioning

confidence: 99%

Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations

Tomatsu

Sawamoto

Shimada

et al. 2015

Expert Opinion on Orphan Drugs

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Introduction Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older. Areas covered Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT. Expert opinion We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues.

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“…No significant impact was seen in the 3‐min stair climb test (3MSCT). In addition, a rapid and sustained reduction in urine KS (uKS) levels and numerical improvements in several other efficacy outcomes, including respiratory function and growth, were observed [Hendriksz et al, [Link]; Hendriksz et al, 2015b]. …”

Section: Introductionmentioning

confidence: 99%

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

Burton

Berger

Lewis

et al. 2015

American J of Med Genetics Pt A

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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.

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Multi-domain impact of elosulfase alfa in Morquio A syndrome in the pivotal phase III trial

Abstract: Treatment with weekly elosulfase alfa led to improvements across most efficacy measures, resulting in clinically meaningful benefits in a heterogeneous study population.

Cited by 67 publications

References 25 publications

Health-related quality of life in mucopolysaccharidosis: looking beyond biomedical issues

Health-related quality of life in mucopolysaccharidosis: looking beyond biomedical issues

Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations

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

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