Raptor Pharmaceutical Corp, a global pharmaceutical company, announced that data from its open label extension study of delayed-release cysteamine bitartrate (PROCYSBI) has been published in the Journal of Paediatrics. The study demonstrated that patients with nephropathic cystinosis who took PROCYSBI for two years were able to sustain optimal cystine control in their white blood cells and preserve kidney function over the long term, and had significant improvements in social, school and total functioning based on validated quality of life measurement scales.

The prospective, controlled, open label, single-arm study followed 40 patients with nephropathic cystinosis treated with PROCYSBI for two years to assess efficacy in cystine depletion in peripheral white blood cells, to assess the dose required to maintain white blood cell (WBC) content of cystine below 1 nmol ½ cystine/mg protein, to measure quality of life using the Paediatric Quality of Life Inventory (PedsQL), change in estimated glomerular filtration rate, and change in height Z-score. The objective was to determine the long-term effects of PROCYSBI therapy in patients with the disease.

Over two years of treatment, the mean WBC cystine was maintained under optimal control of < 1 nmol ½ cystine/mg protein, and the dose of PROCYSBI decreased from 43.5 to 40.1 mg/kg/d (p = .05).

Kidney function deteriorates over time in nephropathic cystinosis patients who often require a kidney transplant early in life. In this study, kidney function as monitored by eGFR remained stable over two years of treatment.

Using the validated PedsQL score, investigators documented a significant and persistent improvement in patients who had switched from immediate-release cysteamine to PROCYSBI, over two years of treatment, in three measures: social function (p = .049), school function (p = .004), and in total function (p = .048). Investigators assessed the subsequent change from all baseline values in the PedsQL and demonstrated that the changes persisted after two years of PROCYSBI therapy. Changes in physical and emotional quality of life scales over the two years of study were not changed.

"Long-term control of WBC cystine depletion below 1 nmol has never been reported in a prospective manner in a cohort of patients," said Craig B. Langman, M.D., the Isaac A. Abt, M.D. professor of Kidney Diseases and head of pediatric kidney diseases at Northwestern University Feinberg School of Medicine and the Ann and Robert H. Lurie Children's Hospital of Chicago, and the lead author on the paper. "Here, with delayed-release cysteamine, we provide two years of data demonstrating disease control, preservation of kidney function, stable somatic growth, and quality of life improvements. These data demonstrate that patients were able to remain adherent to their delayed-release cysteamine therapy for two years, something never before demonstrated in a controlled clinical trial in this population."

There were no unexpected or serious safety concerns attributable to PROCYSBI. All 40 patients experienced one or more treatment-emergent adverse events: GI disorders in 35 (87.5%), emesis in 28 (70.0%), headache in 14 (35.0%), upper respiratory tract symptoms in 9 (22.5%), and diarrhea in 8 (20.0%).

Nephropathic cystinosis comprises 95 per cent of diagnosed cases of cystinosis, a rare, life-threatening metabolic lysosomal storage disorder that causes toxic accumulation of cystine in all cells, tissues, and organs in the body. Elevated cystine leads to progressive, irreversible tissue damage and multi-organ failure, including kidney failure, blindness, muscle wasting and premature death. Nephropathic cystinosis is typically diagnosed in infancy and requires lifelong therapy. Left untreated, the disease is usually fatal by the end of the first decade of life. There are an estimated 500 patients living in the United States with cystinosis, and 2,000 worldwide.

Cystine depletion is the primary treatment strategy for nephropathic cystinosis. However, poor adherence to therapy has been a major challenge resulting in poor sustained control of cystine levels, and patients consequently experience poor clinical outcomes, including kidney insufficiency leading to dialysis and kidney transplantation, muscle wasting and in some cases, premature death.