Opko Health, Inc.,  a multinational biopharmaceutical and diagnostics company,  has submitted a New Drug Application (NDA) for oral Rayaldee to the US Food and Drug Administration (FDA). The NDA requests marketing approval for Rayaldee for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency.

"The submission of this NDA represents a significant milestone in the development of Rayaldee, and it underscores our strong commitment to making improved therapies available to patients who suffer from chronic kidney disease," commented Dr. Phillip Frost, CEO and chairman of Opko. "We believe Rayaldee will be the first product to receive FDA approval for this important indication."

The Rayaldee application is supported by positive data from three randomized, double-blind, placebo-controlled studies and one open-label extension study conducted in the targeted patient population at a total of 105 US sites. These studies met all primary efficacy and safety endpoints, as previously announced.

Rayaldee is a first-in-class oral vitamin D prohormone treatment being developed for SHPT in patients with stage 3 or 4 CKD and vitamin D insufficiency. It has a proprietary modified-release formulation designed to gradually and reliably raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) while avoiding upregulation of CYP24A1, a cytochrome P-450 enzyme which reduces the desired parathyroid hormone (PTH)-lowering efficacy. Gradual elevation of serum total 25-hydroxyvitamin D prevents excessive elevation of serum calcium and related vascular and renal calcification. Such side effects limit the value of current vitamin D hormone therapies. Rayaldee is expected to address the approximately 20 million patients in the US, and many more elsewhere, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency.

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 stages — mild (stage 1) to severe (stage 5) disease — as measured by the kidney's glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the US, including more than 20 million patients with moderate (stages 3 or 4) and severe (stage 5) forms of CKD. In stage 5 CKD, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant for survival.

Vitamin D insufficiency is a condition in which the body has low vitamin D stores, characterized by inadequate blood levels of vitamin D prohormone, known as 25-hydroxyvitamin D. An estimated 70-90% of CKD patients have vitamin D insufficiency, which can lead to SHPT and resultant debilitating bone diseases. Vitamin D insufficiency has been associated with increased mortality in CKD.

SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of PTH. SHPT arises as a result of vitamin D insufficiency or impaired kidney function that prevents sufficient production of vitamin D hormone to properly regulate calcium and phosphorus metabolism, and PTH secretion. Prolonged elevation of blood PTH causes excessive calcium and phosphorus to be released from bone, leading to elevated serum calcium and phosphorus, softening of the bones (osteomalacia) and calcification of vascular and renal tissues. SHPT affects 40-60% of patients with moderate CKD and approximately 90% of patients with severe CKD. Vitamin D therapy for SHPT is associated with reduced mortality in CKD patients.