AnorMED Inc. announced that Fosrenol (lanthanum carbonate), a new phosphate binder for use in dialysis patients licensed to Shire Pharmaceuticals Group plc, has been shown not to cause adverse effects on renal bone disease over 12 months of therapy, according to the most comprehensive controlled bone biopsy study ever undertaken in this field.
This new data was presented for the first time at the international symposium "Advances in Renal Osteodystrophy" in Oviedo, Spain by the principal investigator and leading bone disease specialist Professor Marc De Broe, of the University of Antwerp's Department of Nephrology.
"These new clinical results continue to support our view that Fosrenol, in addition to controlling phosphate levels, may offer additional advantages to patients with chronic kidney disease compared to some currently available agents, such as calcium carbonate," said Dr. Michael Abrams, president and CEO of AnorMED Inc. "Fosrenol is the most advanced product in our product pipeline. This clinical data, along with the first approval in the E.U., anticipated over the next few weeks, are important milestones for AnorMED."
Poor control of blood calcium or phosphate levels in chronic renal failure patients can result in bone disease and secondary hyperparathyroidism. Currently available medications such as calcium or aluminium-based phosphate binders can be associated with new or worsening bone disease. These concerns make it important to monitor carefully the effects of new phosphate binders on bone metabolism. Such a comprehensive investigation into the impact of these treatments has not previously been undertaken and it is very encouraging to see that Fosrenol is well tolerated and may offer important advantages over other phosphate binders based on the results of this study.
These new data demonstrate that treatment with Fosrenol was not associated with any adverse effects on bone over 12 months of continuous therapy. Furthermore, in the lanthanum patients, there was no evolution towards low bone turnover states. This is in contrast to treatment with calcium carbonate and aluminium hydroxide, where low bone turnover has been shown to develop. Earlier research has shown that compared to calcium- containing phosphate binders, Fosrenol produces significantly fewer episodes of hypercalcaemia. Metastatic and vascular calcification, resulting from hypercalcaemia, has well-recognised cardiovascular risks, and significantly contributes to overall morbidity and mortality in dialysis patients.
In this phase III multicentre study, 98 patients who were starting renal dialysis for the first time were randomised to receive either lanthanum carbonate or calcium carbonate (a standard reference treatment), titrated to a dose which was well tolerated and gave acceptable control of serum phosphate (up to 3,750 mg lanthanum carbonate / day or up to 9,000 mg calcium carbonate / day).
Bone biopsies were taken at the beginning and end of the 12-month study period and, at each visit, blood samples were taken to assess phosphate, calcium, parathyroid hormone and other biochemical and haematological parameters. A total of 60 paired biopsies (i.e. baseline and follow-up) were suitable for histological assessment on completion of the study (30 per treatment group).
One important additional finding of the study was the widespread incidence of renal bone disease discovered in patients who were new to dialysis. Pre-treatment baseline examination of patients enrolled on the study found that over 90% of patients had altered bone biology prior to commencing dialysis treatment.
Shire has conducted extensive clinical studies of Fosrenol, in both Europe and the U.S., treating over 1660 patients. Clinical data from these studies will begin to be published during the second half of 2002. Shire expects to receive E.U. marketing approval in mid-year 2002. The median time for other recent FDA Standard Reviews of New Drug Applications have been 12 to 14 months and once Fosrenol is launched, a single-digit royalty on net sales will be payable to AnorMED.
It is estimated that there are approximately 280,000 kidney dialysis patients in the U.S., 225,000 in Europe, 190,000 in Japan and 90,000 in the Pacific Rim region. The majority of these patients will experience elevated blood phosphate levels, described as hyperphosphataemia. If untreated, this elevated phosphate level together with other biochemical disturbances can result in bone disorders known as renal osteodystrophies. Recent clinical data also suggest that excess phosphate may also be associated with the development of cardiovascular disease, which accounts for nearly 50% of all deaths in dialysis patients.
Fosrenol, developed as a convenient chewable tablet, binds to the dietary phosphate in the digestive system. Once bound, the Fosrenol/phosphate complex cannot pass through the system into the blood stream and is eliminated from the body. As a consequence, phosphate absorption from the diet is decreased significantly.