The vitamin D prohormone drug RAYALDEE (OPKO Health, Inc.) has been approved by the FDA for treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D deficiency, as announced in a press release by the company.
A larger proportion of patients treated with RAYALDEE had a reduction of at least 30% in plasma intact parathyroid hormone compared with placebo, and vitamin D insufficiency was corrected in more than 80% of patients treated with RAYALDEE compared with less than 7% of patients receiving placebo. Minor increases in mean serum calcium and phosphorus levels were deemed “clinically irrelevant.” The most common adverse reactions (≥3% and more frequent than placebo) included: anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation.
“RAYALDEE fills a large void in the current treatment options for SHPT in pre-dialysis patients,” stated Charles Bishop, the CEO of OPKO’s Renal Division, in the press release. “The current standard of care is high dose vitamin D supplementation, an approach for treating SHPT that is neither FDA approved nor demonstrated to be safe and effective in this population. SHPT is a progressive disease that becomes increasingly debilitating and difficult to treat, necessitating timely and effective treatment.”
A proprietary modified-release formulation of calcifediol, RAYALDEE is designed to raise serum total 25-hydroxyvitamin D concentrations gradually to targeted levels of at least 30 ng/mL, while avoiding upregulation of CYP24A1, the cytochrome P450 enzyme that catalyzes the degradation of the vitamin D molecule. RAYALDEE is not indicated for patients with stage 5 CKD or end-stage renal disease on dialysis.
While RAYALDEE provides a new option for treating SHPT in patients with stage 3 or 4 CKD and vitamin D deficiency, Dr. Daniel Coyne, MD, Professor of Medicine, Nephrology/Internal Medicine here at Washington University School of Medicine Division of Nephrology, points out that it is unclear if RAYALDEE will actually offer an advantage over our present therapies for SHPT and vitamin D deficiency. “While RAYALDEE normalizes 25(OH)-vitamin D blood levels efficiently, higher doses of nutritional vitamin D (D3, cholecalciferol; or D2, ergocalciferol) are inexpensive and can also do that,” says Coyne. “RAYALDEE suppresses PTH somewhat (mean reduction ~22%*) but this is much less than calcitriol and paricalcitol, two active forms of vitamin D, which lower PTH about 46-52%.”
Whether RAYALDEE will be just another choice for treatment of SHPT and vitamin D deficiency in this target group of patients or whether it proves superior to current treatments will be no doubt be determined in the clinic once it is launched in the United States later this year.