The primary end point — defined as noninferiority of etelcalcetide at achieving >30% reduction from baseline in mean predialysis PTH concentrations during weeks 20 to 27 (noninferiority margin: 12%) — was achieved. Estimated mean difference in proportions achieving this reduction between groups was –10.5% (95% CI, –17.5 to –3.5; P <.001 for noninferiority; P =.004 for superiority).
Furthermore, there was a higher rate of patients in the etelcalcetide arm who achieved >50% reduction in PTH concentrations (52.4% vs 40.2%; P =.001).
“Although efficacy was sustained and relative safety demonstrated over 26 weeks, secondary hyperparathyroidism is a chronic condition often requiring life-long therapy; therefore, longer-term safety data will be required,” Dr Block and researchers wrote.
Clinical and Investigative Implications
In an accompanying editorial,3 John P. Middleton, MD, and Myles Wolf, MD, MMSc, both from the Duke University School of Medicine in Durham, North Carolina, wrote that because etelcalcetide potently reduces PTH, phosphate, and FGF23 concentrations via an administration route that could raise adherence, it offers the best chance yet for a future clinical trial to show that enhanced biochemical control of disordered mineral metabolism results in improved clinical outcomes.
“Such a trial would clearly influence [end-stage renal disease] management directly,” Drs Middleton and Wolf wrote.3 “Indirectly, it could also provide the proof-of-concept confidence needed to fuel a new wave of pharmaceutical innovation to target disordered mineral metabolism when it is first established in earlier stages of chronic kidney disease, perhaps most amenable to treatment, and (currently) free from restrictions imposed by bundled reimbursement.”
Disclosure: Dr Middleton has served as a consultant for or received honoraria from AstraZeneca, Relypsa, and ZS, and received grant support from Bristol-Myers Squibb and Keryx. Dr Wolf has served as a consultant for or received honoraria from Amag, Amgen, Ardelyx, DiaSorin, Incyte, Keryx, Lilly, Pfizer, Sanofi, Ultragenyx, and ZS, and received grant support from Shire.
- Block GA, Bushinsky DA, Cunningham J, et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism. JAMA. 2017;317(2):146-155. doi:10.1001/jama.2016.19456
- Block GA, Bushinsky DA, Cheng S, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism. JAMA. 2017;317(2):156-164. doi:10.1001/jama.2016.19468
- Middleton JP, Wolf M. Second chances to improve ESRD outcomes with a second-generation calcimimetic. JAMA. 2017;317(2):139-141.