The US Food and Drug Administration (FDA) has accepted for review OPKO's New Drug Application (NDA) for calcifediol modified-release capsules (proposed trade name, Rayaldee).

In the NDA, OPKO seeks approval of 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.

"FDA acceptance of this NDA should be cheered by healthcare professionals who care for CKD patients," commented Dr. Kevin J. Martin, director of the division of nephrology at Saint Louis University School of Medicine.

"If approved, Rayaldee will provide a new therapeutic option for controlling elevated parathyroid hormone levels in this large and undertreated patient population."

OPKO expects written notification of NDA acceptance along with the Prescription Drug User Fee Act (PDUFA) date in the FDA's 74-dDay letter, which the company expects to receive by mid-August 2015.

The NDA is supported by 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 an 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 interferes with the desired parathyroid hormone (PTH)-lowering effect. Gradual elevation of serum total 25-hydroxyvitamin D is intended to prevent excessive elevation of serum calcium and related vascular and renal calcification.

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 per cent 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 per cent of patients with moderate CKD and approximately 90 per cent of patients with severe CKD.

OPKO is a multinational biopharmaceutical and diagnostics company that seeks to establish industry leading positions in large, rapidly growing markets by leveraging its discovery, development and commercialization expertise and novel and proprietary technologies.