Etelcalcetide Examined in Hemodialysis Patients With Secondary Hyperparathyroidism

Results of separate randomized trials^1,2 indicate that the use of etelcalcetide in hemodialysis patients with moderate to severe secondary hyperparathyroidism was superior to placebo and noninferior to cinacalcet in reducing parathyroid hormone (PTH) levels at 26 weeks.

The findings were published recently in JAMA.

Etelcalcetide Outperforms Placebo

To better understand the role of intravenous (IV) calcimimetic etelcalcetide on serum PTH concentrations in patients with secondary hyperparathyroidism undergoing hemodialysis, Geoffrey A. Block, MD, of Denver Nephrology, and fellow researchers conducted 2 parallel, phase 3, randomized, placebo-controlled trials (ClinicalTrial.gov identifiers: NCT0178584, NCT01788046).

In all, researchers enrolled 1023 patients (mean age: 58.2 years; 60.4% men) with moderate to severe secondary hyperparathyroidism who were undergoing hemodialysis, of whom 508 were part of trial A and 515 were part of trial B. The 2 trials were the same, according to study methodology, with the exception that researchers collected predialysis and postdialysis laboratory data and electrocardiograms in trial A and only predialysis measurements in trial B.

The proportion of patients attaining >30% reduction from baseline in mean PTH levels during weeks 20 to 27 served as the primary efficacy outcome, while the rate of patients who achieved a mean PTH level ≤300 pg/mL was the secondary efficacy measure.

In trial A, mean PTH concentrations in the etelcalcetide group were 849 pg/mL at baseline and 384 pg/mL during weeks 20 to 27 vs 820 pg/mL at baseline and 897 pg/mL during weeks 20 to 27 in the placebo group.¹ Similar discrepancies between groups were reported in trial B.¹

In addition, significantly more patients in the etelcalcetide arm than the placebo arm achieved the primary end point in trial A (74% vs 8.3%; P <.001) and trial B (75.3% vs 9.6%; P <.001). More patients in the etelcalcetide arm than the placebo arm also achieved levels ≤300 pg/mL in trial A (49.6% vs 5.1%; P <.001) and trial B (53.3% vs4.6%; P <.001); however, rates of muscle spasm, nausea, and vomiting were also higher with etelcalcetide.¹

 “The reduction in PTH was rapid, sustained over 26 weeks, and evident in all evaluated subgroups, with no apparent effect modification by age, sex, race, time since dialysis initiation, geographic region, baseline severity of secondary hyperparathyroidism, or use of vitamin D,” Dr Block and colleagues wrote. “The efficacy results are particularly noteworthy given that patients were already receiving conventional therapy for secondary hyperparathyroidism.”

Etelcalcetide Noninferior to Cinacalcet

Results of a separate study (ClinicalTrials.gov identifier: NCT1896232),² also conducted by Dr Block and colleagues, examined the efficacy and safety of etelcalcetide vs the calcimimetic cinacalcet in 683 patients (mean age: 54.7 years; 56.2% men) with moderate to severe secondary hyperparathyroidism undergoing hemodialysis.

The randomized, double blind, double-dummy active clinical trial included patients who received IV etelcalcetide and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks.