The FDA has issued a complete response letter (CRL) in reply to a new drug application (NDA) for calcifediol modified-release capsules (Rayaldee, Opko Health) as a treatment for secondary hyperparathyroidism (SHPT) in patients with stage-3 or -4 chronic kidney disease (CKD) and vitamin D insufficiency.
The FDA indicated that observations of deficiencies at a third-party contract manufacturer were issued in March 2016 as a result of an FDA field inspection. The observations were not specific to the manufacturing of calcifediol. The CRL did not cite any safety, efficacy, or labeling issues with regard to calcifediol, nor did it request any additional studies to be conducted prior to the FDA’s final decision on approval. In the CRL, the FDA reconfirmed its acceptance of the proprietary name Rayaldee.
The NDA for calcifediol was accepted in July 2015.
Calcifediol is an oral vitamin D prohormone treatment 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 raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) while avoiding upregulation of cytochrome P450-24A1, an enzyme that interferes with the desired parathyroid hormone-lowering effect. The gradual elevation of serum total 25-hydroxyvitamin D is intended to prevent excessive elevation of serum calcium and related vascular and renal calcification.
Sources: Opko Health; March 30, 2016; and Opko Health; July 28, 2015.