Evaluating extended-release calcifediol as a treatment option for chronic kidney disease-mineral and bone disorder (CKD-MBD)

ABSTRACT

Introduction: Extended-release calcifediol (ERC) is an orally administered prohormone of active vitamin D (1,25-dihydroxyvitamin D [1,25D]) designed to safely and sufficiently increase serum total 25-hydroxyvitamin D (25D) to reduce elevated parathyroid hormone (PTH) in patients with non-dialysis-chronic kidney disease (ND-CKD). ERC is currently approved in the United States and Canada.

Areas covered: Herein, key clinical data relating to the pharmacokinetics, pharmacodynamics, efficacy and safety of ERC are reviewed.

Expert opinion: Currently available treatment options for secondary hyperparathyroidism (SHPT) in ND-CKD have limitations: the effectiveness of nutritional vitamin D supplements for reduction of PTH levels is unproven and active (1α-hydroxylated) vitamin D analogues elevate serum calcium, which increases the risk of hypercalcemia and vascular calcification. Clinical studies show that ERC is an effective, well tolerated treatment for SHPT in ND-CKD. ERC gradually raises serum 25D levels, resulting in physiologically regulated increases in serum 1,25D and sustained reductions in PTH, while avoiding clinically meaningful increases in serum phosphorus, calcium and fibroblast growth factor 23. ERC offers a new, effective and well tolerated treatment option for the early management of SHPT in patients with ND-CKD.

KEYWORDS:

• Chronic kidney disease
• secondary hyperparathyroidism
• vitamin D deficiency
• vitamin D insufficiency
• 25-hydroxyvitamin D
• calcifediol
• parathyroid hormone

Acknowledgments

Vifor Fresenius Medical Care Renal Pharma reviewed this manuscript for medical and scientific accuracy.

Article highlights

• Currently available treatment options for secondary hyperparathyroidism (SHPT) in patients with non-dialysis chronic kidney disease (ND-CKD) have efficacy and safety limitations. Nutritional vitamin D supplements do not consistently lower elevated parathyroid hormone (PTH) levels, while active (1α-hydroxylated) vitamin D analogues reduce PTH levels, but are associated with undesired increases in serum phosphorus and calcium.

• Extended-release calcifediol (ERC) is an orally administered, ER formulation of the natural precursor (or prohormone) of active vitamin D (1,25-dihydroxyvitamin D [1,25D]).

• ERC is currently approved in the US and Canada for the treatment of SHPT in adults with stage 3 or 4 chronic kidney disease and vitamin D insufficiency (total serum 25-hydroxyvitamin D [25D] <30 ng/mL).

• Evidence from clinical studies indicate that current clinical guideline targets for vitamin D sufficiency (serum 25D of 20 or 30 ng/mL) are too low, and that higher levels of 25D (>50 ng/mL) are required for effective control of SHPT in ND-CKD patients.

• ERC gradually raises serum 25D to levels >50 ng/mL, resulting in physiologically regulated increases in serum 1,25D and sustained reductions in PTH levels; it achieves this without clinically relevant increases in serum phosphorus and calcium.

• Two randomized, double-blind, placebo-controlled Phase 3 clinical trials and a 26-week subsequent extension study have demonstrated that oral ERC (administered at daily bedtime doses of 30 or 60 µg), is well tolerated and effective for treating SHPT and correcting underlying vitamin D deficiency in patients with stage 3 or 4 CKD. In these studies, ERC had inconsequential impact on serum calcium, phosphorus and FGF23.

• ERC offers physicians a new, effective and well tolerated treatment option for the management of SHPT in patients with ND-CKD.

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Declaration of interest

M Cozzolino has received research grants from AbbVie, Shire, Baxter, Keryx as well as speaker’s honoraria for the participation in scientific meetings from Amgen, Shire, AbbVie, Vifor Pharma and Baxter. M Ketteler has received consulting and lecture honoraria from Amgen, FMC, Medice, Sanofi, Shire, Vifor Fresenius Medical Care Renal Pharma, and Vifor Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical Writing assistance was utilized in this manuscript and funded by Vifor Fresenius Medical Care Renal Pharma.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was supported by Vifor Fresenius Medical Care Renal Pharma. Medical Writing assistance was provided by AXON Communications, London, UK and was funded by Vifor Fresenius Medical Care Renal Pharma.