FDA Approves Rayaldee (Extended-Release Calcifediol) to Treat Hyperparathyroidism in Chronic Kidney Disease

Launch expected in second half of 2016

The FDA has given the nod to Rayaldee (calcifediol extended-release capsules, Opko Health, Inc.) for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage-3 or stage-4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels of less than 30 ng/mL. Rayaldee is a patented extended-release product containing 30 mcg of the prohormone calcifediol (25-hydroxyvitamin D3).

SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of parathyroid hormone (PTH). SHPT occurs 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 levels, osteomalacia, and calcification of vascular and renal tissues. SHPT affects 40% to 60% of patients with moderate CKD and approximately 90% of patients with severe CKD.

Results from two 26-week, phase 3, placebo-controlled, double-blind trials demonstrated that a larger proportion of stage-3 or stage-4 CKD patients with SHPT and vitamin D insufficiency achieved reductions of 30% or greater in plasma-intact PTH (iPTH) when treated with Rayaldee than with placebo. Vitamin D insufficiency was corrected in more than 80% of the patients receiving Rayaldee compared with less than 7% of those receiving placebo. Mean serum calcium and phosphorus levels increased by 0.1 mg/dL during Rayaldee treatment compared with placebo treatment, but these changes were deemed clinically irrelevant. No differences in the efficacy or safety of Rayaldee were observed between patients with stage-3 CKD or stage-4 CKD.

Rayaldee has a patented formulation designed to raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) and to reduce elevated iPTH. Rayaldee is not indicated for patients with stage-5 CKD or end-stage renal disease on dialysis.

The potential adverse effects of Rayaldee include hypercalcemia, which can lead to digitalis toxicity, and adynamic bone disease with a subsequent increased risk of fractures if intact PTH levels are suppressed by Rayaldee to abnormally low levels. Severe hypercalcemia may require emergency attention; symptoms of hypercalcemia include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss. Digitalis toxicity can be potentiated by hypercalcemia of any cause. Excessive administration of Rayaldee can cause hypercalciuria, hypercalcemia, hyperphosphatemia, or oversuppression of intact PTH. Common symptoms of vitamin D overdosage include constipation, decreased appetite, dehydration, fatigue, irritability, muscle weakness, and vomiting. Patients concomitantly taking cytochrome P450 inhibitors, thiazides, cholestyramine, phenobarbital, or other anticonvulsants may require dose adjustments and more-frequent monitoring.

The most common adverse events in clinical trials of Rayaldee included anemia, nasopharyngitis, increased blood creatinine levels, dyspnea, cough, constipation, and congestive heart failure.

The product is expected to be launched in the U.S. in the second half of 2016.

Source: Opko Health; June 21, 2016.