Indication and Limitations of Use:

Parsabiv™ (etelcalcetide) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.

Parsabiv™ has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations.

Close Window
clinical-data

Clinical Data

The demonstrated efficacy and safety of Parsabiv™

2017 KDIGO® guidelines suggest calcimimetics as a first-line treatment option for sHPT.13

Parsabiv™ safety and efficacy were evaluated in 2 placebo-controlled studies1,2,14-18

Study design
clinical-data-study-design-1-desktop
  • Two phase 3, 26-week, multicenter, randomized, double-blind, placebo-controlled clinical studies comparing Parsabiv™ with placebo in patients with CKD on hemodialysis with iPTH > 400 pg/mL and corrected calcium ≥ 8.3 mg/dL (N = 1023)
  • Parsabiv™ or placebo administered three times per week into the venous line of the dialysis circuit at the end of hemodialysis during rinse back or intravenously after rinse back
  • Patients in both treatment arms could be treated with vitamin D sterols and/or phosphate binders, if prescribed
  • Mean baseline iPTH in the Parsabiv™ group and placebo group were 847 pg/mL and 836 pg/mL, respectively
  • During the efficacy assessment period, the average weekly dose of active vitamin D (IV paricalcitol equivalent) was 16.7 μg in the Parsabiv™ group and 14.5 μg in the placebo group
  • The average dose of Parsabiv™ at the time of the efficacy assessment period (defined as weeks 20 through 27, inclusive) was 7.2 mg three times a week
Titration
  • The starting dose of Parsabiv™ was 5 mg TIW at the end of hemodialysis
  • The dose was titrated at weeks 5, 9, 13, and 17 to achieve predialysis serum iPTH ≤ 300 pg/mL. The dose could be increased in 2.5 mg or 5 mg increments based on predialysis iPTH and cCa concentrations
  • The minimum dose was 2.5 mg and the maximum dose was 15 mg
  • Parsabiv™ was withheld if any of the following were observed: iPTH < 100 pg/mL (two consecutive measurements), corrected calcium < 7.5 mg/dL, symptomatic hypocalcemia, other ongoing adverse events
  • Investigators were blinded to central laboratory serum iPTH values, and routine local iPTH monitoring during the study was suspended

TIW = three times a week; iPTH = intact parathyroid hormone.

78% of patients who received Parsabiv™ achieved > 30% reduction in mean PTH19


Vitamin D and/or phosphate binders, if prescribed.16

Initiating Parsabiv™ at PTH > 400 to < 600 pg/mL enabled 73% of patients to achieve the study PTH treatment goal19

Patients achieving study iPTH treatment goal by screening iPTH16,19
Secondary endpoint: in phase 3 trials, overall, 53.4% of Parsabiv™ patients achieved iPTH ≤ 300 pg/mL vs 5.8% of placebo patients during the efficacy assessment period (P < 0.001)19
  • Overall, the average dose of Parsabiv™ during the efficacy assessment period was 7.2 mg three times per week1
  • Patients initiated at screening iPTH < 600 pg/mL had an average dose of 5.7 mg three times per week1
  • Patients initiated at screening iPTH 600 to ≤1000 pg/mL had an average dose of 7.4 mg three times per week1
  • Patients initiated at screening iPTH > 1000 pg/mL had an average dose of 8.7 mg three times per week1

Vitamin D and/or phosphate binders, if prescribed.16

combined-placebo-controlled-studies

Parsabiv™ (etelcalcetide) lowered PTH, phosphate, and corrected calcium19,20

Mean iPTH, phosphate, and corrected calcium over time

scroll right or left to view full charts

iPTH

side-labels-clinical-data-ipth
clinical-data-ipth

P

side-labels-clinical-data-p
clinical-data-p

cCa

side-labels-clinical-data-cca
clinical-data-cca
Parsabiv™ + vitamin D and phosphate binders
Placebo + vitamin D and phosphate binders
Mean % change from baseline19
P < 0.001 vs placebo

With Parsabiv™, PTH, phosphate, and corrected calcium reductions were maintained for up to 78 weeks1

Open-label extension: data pooled for patients receiving Parsabiv™ across two placebo-controlled parent studies and a subsequent open-label extension (OLE) study, starting from the baseline of the parent study until the end or the prespecified cutoff date of the OLE study, whichever was earlier. Weeks 27 to 31 were the 30-day drug-free period (the 30-day follow-up period of the phase 3 study before entry into the extension study).2 During the OLE, the starting dose of Parsabiv™ for all subjects was 5 mg. The Parsabiv™ dose could be increased at OLE weeks 5, 9, 17, 25, 33, 41, and 49 to a maximum dose of 15 mg to achieve predialysis serum iPTH ≤ 300 pg/mL while maintaining appropriate serum cCa concentrations. Investigators were blinded to iPTH results during the first 10 weeks of treatment. Subsequent dose adjustment was determined by the investigator per protocol guidelines.21

Values represent mean iPTH, P, cCa during efficacy assessment period defined as weeks 20 through 27, inclusive.19 Vitamin D and/or phosphate binders, if prescribed.16 Value represents iPTH, P, cCa measured at the first hemodialysis session in week 79.20

adverse-reactions

Adverse reactions reported in ≥ 5% of Parsabiv™ (etelcalcetide)‑treated patients1

Combined placebo-controlled studies

Included adverse reactions reported with at least 1% greater incidence in the Parsabiv™ group compared to the placebo group. Asymptomatic reductions in corrected serum calcium between 8.3 mg/dL and > 7.5 mg/dL (clinically significant reductions that required medical management) or reductions in calcium below 7.5 mg/dL. Symptomatic reductions in corrected serum calcium < 8.3 mg/dL. Paresthesia includes preferred terms of paresthesia and hypoesthesia.

Discontinuations
  • Overall, in placebo-controlled studies, 1.8% of patients in the Parsabiv™ group and 2.5% of patients in the placebo group discontinued treatment due to an adverse event22
Low serum calcium
  • Most events of blood calcium decrease or hypocalcemia were mild or moderate in severity in both the placebo and Parsabiv™ groups17,23
  • In combined placebo-controlled studies, 1% of patients who received Parsabiv™ discontinued treatment due to low corrected serum calcium vs 0% with placebo1

A Detailed Look at the Efficacy and Safety of Parsabiv™



The Safety Profile of Parsabiv™ in Clinical Trials

Important Safety Information

Contraindication: Parsabiv™ (etelcalcetide) is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred.

Hypocalcemia: Parsabiv™ lowers serum calcium and can lead to hypocalcemia, sometimes severe. Significant lowering of serum calcium can cause QT interval prolongation and ventricular arrhythmia. Patients with conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv™. Closely monitor corrected serum calcium and QT interval in patients at risk on Parsabiv™.

Significant reductions in corrected serum calcium may lower the threshold for seizures. Patients with a history of seizure disorder may be at increased risk for seizures if they develop hypocalcemia due to Parsabiv™. Monitor corrected serum calcium in patients with seizure disorders on Parsabiv™.

Concurrent administration of Parsabiv™ with another oral calcimimetic could result in severe, life-threatening hypocalcemia. Patients switching from cinacalcet to Parsabiv™ should discontinue cinacalcet for at least 7 days prior to initiating Parsabiv™. Closely monitor corrected serum calcium in patients receiving Parsabiv™ and concomitant therapies known to lower serum calcium.

Measure corrected serum calcium prior to initiation of Parsabiv™. Do not initiate in patients if the corrected serum calcium is less than the lower limit of normal. Monitor corrected serum calcium within 1 week after initiation or dose adjustment and every 4 weeks during treatment with Parsabiv™. Measure PTH 4 weeks after initiation or dose adjustment of Parsabiv™. Once the maintenance dose has been established, measure PTH per clinical practice.

Worsening Heart Failure: In Parsabiv™ clinical studies, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. Closely monitor patients treated with Parsabiv™ for worsening signs and symptoms of heart failure.

Upper Gastrointestinal Bleeding: In clinical studies, 2 patients treated with Parsabiv™ in 1253 patient years of exposure had upper gastrointestinal (GI) bleeding at the time of death. The exact cause of GI bleeding in these patients is unknown and there were too few cases to determine whether these cases were related to Parsabiv™.

Patients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may be at increased risk for GI bleeding with Parsabiv™. Monitor patients for worsening of common Parsabiv™ GI adverse reactions and for signs and symptoms of GI bleeding and ulcerations during Parsabiv™ therapy.

Adynamic Bone: Adynamic bone may develop if PTH levels are chronically suppressed.

Adverse Reactions: In clinical trials of patients with secondary HPT comparing Parsabiv™ to placebo, the most common adverse reactions were blood calcium decreased (64% vs. 10%), muscle spasms (12% vs. 7%), diarrhea (11% vs. 9%), nausea (11% vs. 6%), vomiting (9% vs. 5%), headache (8% vs. 6%), hypocalcemia (7% vs. 0.2%), and paresthesia (6% vs. 1%).

Indication

Parsabiv™ (etelcalcetide) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.

Limitations of Use:

Parsabiv™ has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations.

References: 1. Parsabiv™ (etelcalcetide) prescribing information, Amgen. 2. Data on file, Amgen; [Summary of Clinical Efficacy; 2015]. 3. Goodman WG. Calcium and phosphorus metabolism in patients who have chronic kidney disease. Med Clin North Am. 2005;89:631-647. 4. Hruska KA, Mathew S, Lund R, Qiu P, Pratt R. Hyperphosphatemia of chronic kidney disease. Kidney Int. 2008;74:148-157. 5. Wesseling-Perry K, Harkins GC, Wang HJ, et al. The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84). J Clin Endocrinol Metab. 2010;95:2772-2780. 6. Komaba H, Shiizaki K, Fukagawa M. Pharmacotherapy and interventional treatments for secondary hyperparathyroidism: current therapy and future challenges. Expert Opin Biol Ther. 2010;10:1729-1742. 7. Goodman WG, Quarles LD. Vitamin D, calcimimetics, and phosphate-binders. In: Brenner BM, Levine SA, eds. Brenner & Rector’s The Kidney. 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1904-1927. 8. Alexander ST, Hunter T, Walter S, et al. Critical cysteine residues in both the calcium-sensing receptor and the allosteric activator AMG 416 underlie the mechanism of action. Mol Pharmacol. 2015;88:853-865. 9. Sensipar® (cinacalcet) prescribing information, Amgen. 10. Data on file, Amgen; [Report R20130052; 2014]. 11. Chen P, Olsson Gisleskog P, Perez-Ruixo JJ, et al. Population pharmacokinetics and pharmacodynamics of the calcimimetic etelcalcetide in chronic kidney disease and secondary hyperparathyroidism receiving hemodialysis. CPT Pharmacometrics Syst Pharmacol. 2016;5:484-494. 12. Ma JN, Owens M, Gustafsson M, et al. Characterization of highly efficacious allosteric agonists of the human calcium-sensing receptor. J Pharmacol Exp Ther. 2011;337:275-284. 13. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2017;7:1–59. 14. Data on file, Amgen; [Clinical Study Report 20120229; 2014]. 15. Data on file, Amgen; [Clinical Study Report 20120230; 2014]. 16. 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. 17. Data on file, Amgen; [Integrated Summary of Safety; 2015]. 18. Data on file, Amgen; [Average Weekly Dose Vitamin D; 2017]. 19. Data on file, Amgen; [Combined Phase 3 Lab Values Multiple Imputation Approach; 2017]. 20. Data on file, Amgen; [Combined Phase 3 Lab Values Over Time; 2016]. 21. Data on file, Amgen; [Clinical Study Report 20120231; 2015]. 22. Data on file, Amgen; [Integrated Summary of Efficacy; 2015]. 23. Data on file, Amgen; [Summary of Clinical Safety; 2015]. 24. Centers for Medicare & Medicaid Services (CMS), HHS. Medicare Program; End-Stage Renal Disease Prospective Payment System, and Quality Incentive Program. Final Rule. Fed Regist. 2015;80(215):68967-69077.