Shire Human Genetic Therapies has announced that results from an observational study published in the June 2009 print issue of Genetics in Medicine demonstrate that enzyme replacement therapy (ERT) with Replagal 0.2mg/kg is effective in treating some of the signs and symptoms of Fabry disease in women.
Clinical benefits were measured, including stabilisation of kidney function and improvement in patients with stage 2 CKD, improvement in cardiac structure in some groups of patients, and reduction in pain and burden of disease. Authors concluded that this observational study, which included 36 women and lasted for four years, indicates that women with signs and symptoms of Fabry disease should be considered for ERT with agalsidase alfa, noting that the patient population studied may not be representative of the general Fabry disease female population.
“Our research has generated meaningful, measureable data which shows that long-term treatment with agalsidase alfa stabilizes kidney function and improves heart function. This may result in important benefits for Fabry women, such as the reduced risk of heart failure,” said Christoph Kampmann, co-author of the study, Centre for Lysosomal Storage Diseases, Children’s Hospital of the Universitätsmedizin Johannes Gutenberg University, Mainz, Germany.
Because women are commonly described as “carriers” of Fabry disease, the true burden of their disease is often under estimated, which leads to delayed diagnosis and initiation of treatment, even though it is documented that without treatment, their lifespan is typically reduced by 15 years compared to the general population.
“Like Dr Whybra et al physicians in the UK recognise that females can indeed carry a significant burden of Fabry disease requiring swift and correct diagnosis and management by an expert centre. This long term study allows us to better understand how women suffering from the symptoms of Fabry disease may benefit from enzyme replacement therapy with agalsidase alpha and is consistent with our findings in the female patients we treat here,” said Derralynn Hughes, Senior Lecturer in Haematology, Lysosomal Storage Disorder Unit, Royal Free Hospital, London.
Key findings from the study:
Kidney function – Stabilisation or improvement in kidney function was found in more than 90 percent of the women in the study. Average eGFR (estimated glomerular filtration rate) was 91.0 ± 31.2 mL/min/1.73 m2/year at baseline and remained stable throughout the study. A subgroup of patients with moderately reduced renal function at baseline (Stage 2 CKD, eGFR >60 and <90ml/min/1.73m2) demonstrated a significant increase in eGFR after 1 year of treatment, which was sustained through four years.
Reduction in proteinuria was also noted in patients with a baseline excretion of >300mg/day.
Cardiac structure and function – LVM was significantly reduced in patients with baseline LVH after one year of Replagal, and remained reduced through the four years, with 52% of them showing decreases of LVM in excess of 20%. In addition, treatment with Replagal resulted in clinical improvement of symptoms of heart failure for nearly one-third of the patients who were classified as having NYHA Class III heart failure at baseline. After four years of treatment with agalsidase alfa, only one patient remained in NYHA classification III, and no patients progressed to a more severe stage of heart failure.
Pain and burden of disease – Significant benefits with regard to severity of disease and quality of life were demonstrated. Mainz Severity Score Index (MSSI) significantly improved after 12 months of treatment (p< 0.01) and showed continued improvement over four years. Importantly, 12 out of 36 patients (33%) patients exhibited decreases in MSSI scores that moved them to a lower range of severity. Reduced Brief Pain Inventory “pain at worst” was observed: score at baseline was 4.6± 2.9 and declined to 3.3± 2.9 after 12 months (p=0.001).