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

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.

Evaluation of Therapies for Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease.

Introduction: Parathyroid hormone-lowering responses after administration of three different therapies capable of raising serum total 25-hydroxyvitamin D (25OHD) were evaluated in patients with secondary hyperparathyroidism (SHPT), vitamin D insufficiency (VDI), and stage 3 or 4 chronic kidney disease (CKD).

Methods: Sixty-nine adult subjects with intact parathyroid hormone (iPTH) ≥85 and <500 pg/mL and VDI (25OHD <30 ng/mL) were randomized after ≥4-week washout to 2 months of open-label treatment with: (1) extended-release calcifediol (ERC) 60 μg/day; (2) immediate-release calcifediol (IRC) 266 μg/month; (3) high-dose cholecalciferol (HDC) 300,000 IU/month; or (4) paricalcitol plus low-dose cholecalciferol (PLDC) 1 or 2 μg and 800 IU/day, used as reference hormone replacement therapy. Serum 25OHD, calcium (Ca), phosphorus (P), plasma iPTH, and adverse events were monitored weekly.

REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.

Objectives: This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19.

Methods: COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily.

Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients.

Introduction: Extended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D.