OPKO Health, Inc., a multinational biopharmaceutical and diagnostics company, has entered into a definitive agreement to acquire Canada-based Cytochroma Inc. whose lead products, both in phase III clinical trials, are Replidea (coded CTAP101 capsules), a vitamin D prohormone to treat secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency, and Alpharen, a non-absorbed phosphate binder to treat hyperphosphatemia in dialysis patients.
Replidea has been shown in a phase II b clinical trial to effectively and safely treat SHPT and the underlying vitamin D insufficiency in pre-dialysis patients. Vitamin D insufficiency arises in CKD due to the abnormal upregulation of CYP24, an enzyme which destroys vitamin D and its metabolites. Studies in CKD patients have demonstrated that currently available over-the-counter and prescription vitamin D products cannot reliably raise blood vitamin D prohormone levels or effectively treat SHPT.
"OPKO intends to market Replidea along with our proprietary point-of-care vitamin D diagnostic test currently in development," stated Phillip Frost, MD, CEO and Chairman. "We envision these remarkable products as part of the foundation for a new and markedly improved standard of care for chronic kidney disease patients having SHPT and/or hyperphosphatemia."
Alpharen has been shown safe and effective in treating hyperphosphatemia in the phase II and III clinical trials undertaken to date in dialysis patients. Hyperphosphatemia (elevated serum phosphorus) exacerbates SHPT and promotes bone disease, soft tissue mineralization and progression of kidney disease. Approximately 90 per cent of dialysis patients in the United States require regular treatment.
Cytochroma's officers, including Charles W Bishop, PhD, CEO, an authority on developing and commercializing successful new vitamin D therapies, and Eric J. Messner, MBA, having a noteworthy track record in pharmaceutical business development and in marketing and sales in the CKD arena, will join the OPKO management team. Prior to Cytochroma, Dr Bishop and Messner held key positions at Bone Care International, Inc., a leader in vitamin D therapeutics acquired by Genzyme Corporation, now a division of Sanofi.
CKD is a condition characterized by a progressive decline in kidney function. The kidney is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. CKD is classified in five different stages — mild (stage 1) to severe (stage 5) disease — as measured by the kidney's glomerular filtration rate.
Vitamin D insufficiency is a condition in which blood levels of vitamin D prohormones, collectively known as 25-hydroxyvitamin D, are inadequate. An estimated 70-90 per cent of CKD patients have vitamin D insufficiency which can lead to SHPT and its debilitating consequences.
SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of parathyroid hormone (PTH). SHPT arises as a result of vitamin D insufficiency or impaired kidney function. Prolonged elevation of blood PTH causes excessive calcium and phosphorus to be released from bone, leading to elevated serum calcium and phosphorus levels, softening of the bones (osteomalacia) and calcification of vascular and renal tissues.
Hyperphosphatemia, or elevated serum phosphorus, is common in dialysis patients and tightly linked to the progression of SHPT. The kidneys provide the primary route of excretion for excess phosphorus absorbed from ingested food. As kidney function worsens, serum phosphorus levels increase and directly stimulate PTH secretion. Stage 5 CKD patients must reduce their dietary phosphate intake and usually require regular treatment with phosphate binding agents to lower serum phosphorus to meet the recommendations of the National Kidney Foundation's Clinical Practice Guidelines that serum phosphorus levels should be maintained at < 5.5 mg/dL.