Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis

• Published in: Pediatric nephrology (Berlin, West) Vol. 35; no. 9; pp. 1679 - 1697
• Main Authors: Warady, Bradley A., Ng, Eric, Bloss, Laura, Mo, May, Schaefer, Franz, Bacchetta, Justine
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2020; Springer; Springer Nature B.V; Springer Verlag
• Subjects: Adolescent; Bone diseases; Calcification (ectopic); Calcimimetic Agents - administration & dosage; Calcimimetic Agents - adverse effects; Calcium homeostasis; Calcium phosphates; Child; Child, Preschool; Children; Chronic kidney failure; Cinacalcet; Cinacalcet - administration & dosage; Cinacalcet - adverse effects; Clinical trials; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Complications and side effects; Dialysis; Diseases; Dosage and administration; Double-Blind Method; Drug therapy; Equivalence Trials as Topic; Female; Fractures; Hemodialysis; Homeostasis; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary - drug therapy; Hyperparathyroidism, Secondary - etiology; Kidney diseases; Life Sciences; Male; Medicine; Medicine & Public Health; Minerals; Nephrology; Original; Original Article; Parathyroid; Parathyroid hormone; Pediatrics; Phosphorus; Randomized Controlled Trials as Topic; Renal Dialysis - adverse effects; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - therapy; Risk factors; Sterols; Supplements; Testing; Urology; Vitamin D; What's New in Dialysis; United States; Dialysis; Cinacalcet; sHPT; Pediatric; CKD-MBD
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-020-04516-4

Background Secondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. A significant proportion of these children develop CKD-mineral and bone disorder (CKD-MBD), associated with an increased risk of fractures and vascular calcification. The standard of care for sHPT in children includes vitamin D sterols, calcium supplementation, and phosphate binders. Several agents are approved for sHPT treatment in adults undergoing dialysis, including vitamin D analogs and calcimimetics, with limited information on their safety and efficacy in children. The calcimimetic cinacalcet is approved for use in adults with sHPT on dialysis, but is not approved for pediatric use outside Europe. Methods This review provides dosing, safety, and efficacy information from Amgen-sponsored cinacalcet pediatric trials and data from non-Amgen sponsored clinical studies. Results The Amgen cinacalcet pediatric clinical development program consisted of two Phase 3 randomized studies, one Phase 3 single arm extension study, one open-label Phase 2 study, and two open-label Phase 1 studies. Effects of cinacalcet on PTH varied across studies. Overall, 7.4 to 57.1% of subjects who received cinacalcet in an Amgen clinical trial attained PTH levels within recommended target ranges and 22.2 to 70.6% observed a ≥ 30% reduction in PTH. In addition, significant reductions in PTH were demonstrated in all non-Amgen-supported studies. Conclusions To help inform the pediatric nephrology community, this manuscript contains the most comprehensive review of cinacalcet usage in pediatric CKD patients to date.