By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a parenteral, synthetic peptide calcium-sensing receptor agonist (calcimimetic) for the treatment of patients suffering from chronic kidney disease and who are receiving hemodialysis. It is the second calcimimetic to be approved by the FDA for this indication, the first being cinacalcet. These agents increase the sensitivity of the calcium-sensing receptors in the parathyroid gland, resulting in lower parathyroid hormone, serum calcium, and serum potassium levels. Etelcalcetide is marketed as Parsabiv.
Etelcalcetide is indicated for secondary hyperparathyroidism in adult patients presenting with chronic kidney disease and who are on hemodialysis.1
The recommended starting dose is 5 mg administered through intravenous bolus injection three times per week at the end of hemodialysis treatment.1 Maintenance dose is individualized and determined by titration based on parathyroid hormone (PTH) and corrected serum calcium response. The dose range is 2.5-15 mg three times per week. Etelcalcetide is available as 2.5 mg/0.5 mL, 5 mg/mL, and 10 mg/mL single-dose vials.
Etelcalcetide appears to be more effective than cinacalcet as a higher proportion of patients achieved more than a 50% reduction in PTH level.2 Etelcalcetide features a long elimination half-life, permitting three-times-per-week dosing, compared to daily oral dosing for cinacalcet.
The most common adverse event is related to the extension of the drug’s pharmacology: a decrease in blood calcium. This can be severe and can cause paresthesias, myalgias, muscle spasm, seizures, QT prolongation, and ventricular arrhythmias.1 Heart failure requiring hospitalization has been reported (2% vs. 1% in placebo). Other common adverse events include diarrhea and nausea.
The efficacy and safety of etelcalcetide were determined in two randomized, double-blind, placebo-controlled, 26-week studies in subjects presenting with moderate to severe secondary hyperparathyroidism with chronic kidney disease.1,3 The authors of the first study randomized 254 patients to etelcalcetide and 254 to placebo. In the second study, the groups were 255 and 260, respectively. The starting dose was 5 mg three times per week at the end of hemodialysis and titrated every four weeks until week 17 to a maximum dose of 15 mg three times per week to a target PTH level of ≤ 300 pg/mL. Administration was temporarily suspended if there were two consecutive PTH levels < 100 pg/mL, and the dose was not increased if PTH levels were ≤ 300 pg/mL, corrected serum calcium < 8.3 mg/dL, symptomatic hypocalcemia occurred, or at the discretion of the investigator. The primary endpoint was the proportion of subjects with a > 30% reduction in PTH levels from baseline to the efficacy assessment (mean levels for week 20-27, inclusive). The secondary endpoint was the proportion with PTH < 300 pg/mL. In both studies, the primary endpoint was significantly higher, with > 30% reduction with etelcalcetide vs. placebo (77% vs. 11% and 79% vs. 11%). For the secondary endpoint, the values were 52% vs. 6% and 56% vs. 5%. In a 26-week comparative study, etelcalcetide (n = 340) was compared to oral cinacalcet (30 mg daily; n = 343) in a noninferiority design.3 Although noninferiority was established, with primary endpoint of 30% reduction in PTH, etelcalcetide showed a greater reduction in PTH levels (52.4% vs. 40.2%) from baseline and reduction in certain markers of high-turnover bone diseases. The long-term safety and effectiveness of etelcalcetide remains to be determined.
Hyperparathyroidism is a common complication of chronic kidney disease. This condition leads to cardiovascular and bone complications.4 Management ranges from low phosphorus diet, phosphate binders, vitamin D analogs, to calcimimetics. A Cochrane review suggests that cinacalcet therapy may reduce the need for parathyroidectomy in adults with dialysis and elevated PTH but does not improve all-cause or cardiovascular mortality.5 Etelcalcetide is a potentially more effective calcimimetic agonist, although it requires intravenous administration vs. oral administration of cinacalcet. However, this can be conveniently timed with hemodialysis treatment. The cost of etelcalcetide is not yet available.
- Parsabiv Prescribing Information. Amgen. February 2017.
- Block GA, Bushinsky DA, Cheng S, et al. Effect of etelcalcetide vs. cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: A randomized clinical trial. JAMA 2017;317:156-164.
- Block GA, Bushinsky DA, Cunningham J, et al. Effect of etelcalcetide vs. placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: Two randomized clinical trials. JAMA 2017;317:146-155.
- Yuen NK, Ananthakrishnan S, Campbell MJ. Hyperparathyroidism of renal disease. Perm J 2016;20:78-83.
- Ballinger AE, Palmer SC, Nistor I, et al. Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients. Cochrane Database Syst Rev 2014;(12):D0062554.