Treatment of mucopolysaccharidosis type II (Hunter syndrome) with idursulfase: the relevance of clinical trial end points

Abstract

The current treatment of mucopolysaccharidosis type II (MPS II, Hunter syndrome) is enzyme replacement therapy with recombinant idursulfase (Elaprase®). The efficacy of ERT was established based primarily on reduction in urine glycosaminoglycans:creatinine (GAG:Cr) ratio and improvement in a composite score of predicted forced vital capacity (FVC% predicted) and 6-min walk-test distance (6MWT). We retrospectively reviewed these parameters in 11 boys with MPS II treated with idursulfase between April 2007 (or the time of diagnosis) and February 2010. Some results were inconsistent with published trial data, and there was only a small number of analyzable results obtained for the FVC% predicted and 6MWT. A major drawback was the high prevalence of neurological involvement and young age of patients in the study cohort compared with the clinical trials. This study emphasizes the limitations of the current tools utilized to monitor ERT efficacy and MPS II disease burden in clinical practice.

The role of enzyme replacement therapy in severe Hunter syndrome—an expert panel consensus

“…Some physicians have attempted to use clinical trial endpoints, but these were developed for patients with no cognitive involvement. Patients with cognitive impairment are most often unable to comprehend and cooperate with testing [9]. For example, such patients cannot independently perform the 6-min walk test (6MWT), and the results of a “parent-assisted” 6MWT are not meaningful for evaluating mobility and endurance in severely affected patients and should not be used.…”

Eficácia e segurança da terapia com idursulfase em pacientes com mucopolissacaridose tipo II, com e sem comparação com placebo: revisão sistemática e metanálise

“…Houve redução de valores estatisticamente significativa, em comparação ao placebo ou aos valores pré-TRE 13,14,16 . É interessante observar que muitos pacientes atingem os valores normais após alguns meses de tratamento 13 , mas tais mudanças parecem manter-se num platô a partir de então 16 , sugerindo que as manifestações da doença podem estabilizar-se com o tempo ou, o que parece mais provável, a excreção urinária de GAGs não teria utilidade como ferramenta para monitorização da TRE a longo prazo 30 .…”

The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders

“…ADA have been documented in all ERTs (Ponder 2008;Biggeretal2015), but their clinical impact is often difficult to gauge. This difficulty arises from the lack of uniformity in clinical investigation, the heterogeneous phenotype of lysosomal storage disorders and the relatively insensitivity of currently available clinical scoring systems (Glamuzina et al 2011)s u c ha st h e6m i n u t ew a l kt e s ta n d biomarkers such as urinary GAG concentration or urinary GB3. It is therefore unsurprising that the disease in which the effect of anti-ERT antibodies has been most clearly demonstrated, infantile onset Pompe disease, is the most homogenous and most acutely progressive.…”