Extended-Release Calcifediol: A Data Journey from Phase 3 Studies to Real-World Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism

Nephron. 2024;148(10):657-666. doi: 10.1159/000538818. Epub 2024 Apr 24.

Abstract

Background: Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI).

Summary: This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D (25(OH)D) and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled phase 3 per-protocol populations, 74% of the ERC cohort were uptitrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH.

Key messages: These data establish a "continuum" of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

Keywords: 25-Hydroxyvitamin D; Chronic kidney disease-MBD; Extended-release calcifediol; Parathyroid hormone; Secondary hyperparathyroidism.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcifediol* / blood
  • Clinical Trials, Phase III as Topic
  • Delayed-Action Preparations*
  • Humans
  • Hyperparathyroidism, Secondary* / blood
  • Hyperparathyroidism, Secondary* / drug therapy
  • Hyperparathyroidism, Secondary* / etiology
  • Parathyroid Hormone / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / drug therapy

Substances

  • Calcifediol
  • Delayed-Action Preparations
  • Parathyroid Hormone
  • Vitamin D

Grants and funding

Medical writing support for this manuscript was funded by Vifor Fresenius Medical Care Renal Pharma Ltd., Switzerland. Studies were sponsored by OPKO Pharmaceuticals.