Enzyme replacement therapy for mucopolysaccharidosis VI: long‐term cardiac effects of galsulfase (Naglazyme^®) therapy

Abstract

Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme®). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those ≥12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6–1.9 SD greater than normal, was present for ages both <12 and ≥12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those <12 years. For those ≥12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those <12 years of age.

Are new models needed to optimize the utilization of new medicines to sustain healthcare systems?

“…Whilst long-term treatment has been shown in studies to reduce progression and morbidity (109), currently funding all 10 patients in Lithuania with this condition would represent 17% of the total in-patient budget for medicines and medical aids and 3% of total reimbursed ambulatory care pharmaceutical expenditure. Pressure is being placed on the Ministry of Health and Health Insurance Fund to reimburse galsulfase for these patients despite concerns with its value.…”

Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux–Lamy syndrome)—10‐year follow‐up of patients who previously participated in an MPS VI survey study

“…An analysis of pooled data from the clinical trial program showed improvement in pulmonary function tests and growth velocity in patients (n=56, mean age approximately 12 years, range 5 to 29 years) who received ERT for up to 240 weeks [Decker et al, 2010; Harmatz et al, 2010]. Similarly, long-term ERT of up to 96 weeks reduced intraventricular septal hypertrophy and prevented progression of cardiac valve abnormalities in patients <12 years of age [Braunlin et al, 2012]. While the clinical trials and extension studies suggest significant clinical benefit of galsulfase treatment in MPS VI, the Resurvey Study provides information on the long-term effects of galsulfase treatment (ie, up to mean 6.8 years) on the natural progression of MPS VI.…”

Clinical Evolution After Enzyme Replacement Therapy in Twins with the Severe Form of Maroteaux–Lamy Syndrome

“…The GAG levels remained between 6 and 10 mg/mmol of creatinine up to the time of writing, above the normal values of <4 mg/mmol of creatinine (Braunlin et al 2013).…”

“…In particular, the left ventricular hypertrophy and functional abnormalities of the mitral and aortic valves are progressive in individuals who are not treated (Braunlin et al 2013). These abnormalities are stabilized by galsulfase treatment (Brands et al 2013;Giugliani et al 2014).…”