Indications 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. Read More
  • Sensipar® (cinacalcet) is indicated for the treatment of secondary HPT in adult patients with CKD on dialysis.
  • 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.
  • Sensipar® is not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia. Close
Read Less

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. Read More
  • 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
Read Less
$name
Choosing Parsabiv®:
The clinical benefits of the first and only IV calcimimetic1
  • Placebo-controlled studies

  • Head-to-head study

Parsabiv® safety and efficacy were evaluated in 2 placebo-controlled
studies1-6

Study Design

  • *Stratified by region, mean screening iPTH, and recent oral cinacalcet use.
  • 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 TIW 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 EAP, 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 EAP (defined as weeks 20 through 27, inclusive) was 7.2 mg TIW

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 PTH values, and routine local PTH monitoring during the study was suspended
EAP = efficacy assessment phase; TIW = three times a week.

Approximately 7 times more patients given Parsabiv® achieved > 30% reduction in mean PTH7

 

*Vitamin D and/or phosphate binders, if prescribed.5

One-third of patients given Parsabiv® had a reduction* in PTH by week 4—and by week 8 that number nearly doubled8

Post-hoc analysis: Time to first occurrence* of > 30% reduction in iPTH from combined placebo-controlled studies

Parsabiv® + vitamin D and/or phosphate binders;
n = 509

Placebo + vitamin D and/or phosphate binders;
n = 514

  • *Timepoint when > 30% reduction in iPTH was first observed.
  • †Vitamin D and/or phosphate binders, if prescribed.5

Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.

Rolling averages of 3 iPTH values (from previous, current, and next visit) were used.

  • 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

Parsabiv® provided significant reductions across 3 key
sHPT lab values vs placebo7,9,*

Mean iPTH, phosphate, and corrected calcium over time

SCROLL TO VIEW FULL CHART

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Parsabiv® + vitamin D and/or phosphate binders§

Placebo + vitamin D and/or phosphate binders§

Switched from placebo in parent studies to Parsabiv® + vitamin D and/or phosphate binders§

  • *P < 0.001 (mean percent change in EAP, defined as weeks 20 through 27).
  • †Values represent mean iPTH during EAP, defined as weeks 20 through 27, inclusive.7
  • ‡Value represents iPTH measured at the first hemodialysis session in week 79.9
  • §Vitamin D and/or phosphate binders, if prescribed.5

Data pooled 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.10

Absolute (mean %) change from baseline

P < 0.001 vs placebo


When initiated at PTH > 400 to < 600 pg/mL, 73% of patients
given Parsabiv® achieved the study PTH treatment goal7

Subgroup analysis: Patients achieving study iPTH treatment goal by screening iPTH5,7

Parsabiv® + vitamin D and/or phosphate binders*

Placebo + vitamin D and/or phosphate binders*

  • *Vitamin D and/or phosphate binders, if prescribed.5

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 phase (P < 0.001).

The role of Parsabiv® in the treatment of sHPT

Parsabiv® was evaluated in a head-to-head study vs oral Sensipar® (cinacalcet) tablets11,12

Study Design

*Stratified by region and screening iPTH.
  • A phase 3, 26-week, randomized, active-controlled, double-blind, double-dummy study comparing Parsabiv® with Sensipar® in patients with CKD on hemodialysis with iPTH > 500 pg/mL and corrected calcium ≥ 8.3 mg/dL; N = 683
  • Parsabiv® IV TIW + daily oral placebo vs daily oral Sensipar® + placebo IV TIW for 26 weeks
  • Mean baseline iPTH in the Parsabiv® group and Sensipar® group were 1092 pg/mL and 1139 pg/mL, respectively
  • The average weekly dose of investigational product during the EAP (defined as weeks 20 through 27, inclusive) was 21 mg for Parsabiv® and 405 mg for Sensipar®
  • Adherence to investigational product through 26-week study period was:
    • 97% for Parsabiv®
    • 94% for Sensipar®

Titration11

  • Parsabiv® dose uptitrated from 5 mg in 2.5 mg or 5 mg increments, up to a maximum dose of 15 mg, at weeks 5, 9, 13, and 17 to target predialysis 100 ≤ iPTH ≤ 300 pg/mL while maintaining cCa ≥ 8.3 mg/dL
  • Sensipar® dose uptitrated from 30 mg daily in 30 mg increments, up to a maximum dose of 180 mg daily, at weeks 5, 9, 13, and 17 to target predialysis 100 ≤ iPTH ≤ 300 pg/mL while maintaining cCa ≥ 8.3 mg/dL
  • 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 drug-related adverse events
  • Investigators were blinded to central laboratory serum iPTH values, and routine local iPTH monitoring during the study was suspended

Important Study Information

  • At trial end, average Parsabiv® doses were higher than Sensipar® doses (relative to each product’s respective maximally recommended dose) and a greater proportion of Parsabiv®-treated subjects achieved a maximally recommended dose
  • The Parsabiv® arm had11:
    • A higher relative starting dose
    • Higher relative dose increments per dose escalation steps
    • Fewer dose steps needed to reach the maximally recommended dose
  • No differences in tolerability were identified to explain the lack of dose adjustment in the Sensipar® arm
EAP = efficacy assessment phase; TIW = three times a week.

Parsabiv® and Sensipar® patients who achieved a > 30% reduction from baseline in mean PTH11,12

Parsabiv® was non-inferior to Sensipar® with respect to the proportion of patients who achieved a > 30% reduction from baseline in mean iPTH during the EAP (77.9% vs 63.9%; estimated treatment difference of -10.5%; 95% CI: -17.45%, -3.51%); P < 0.001.11,12

*Vitamin D and/or phosphate binders, if prescribed.11

Given the single, limited-duration (26-week) study design and important study information, these data should not be interpreted as providing evidence of superiority of Parsabiv® to Sensipar®. The potential impact of the difference between treatment groups on clinical outcomes has not been studied, and the clinical meaningfulness of such a difference is unknown.

Evaluating additional endpoints in the head-to-head study

Because the primary endpoint was met, the statistical analysis plan called for the sequential testing of the key secondary endpoints, including mean number of days of vomiting or nausea per week in the first 8 weeks.

  • No statistically significant difference between the two groups was observed for the secondary endpoint evaluating the mean number of days of vomiting or nausea per week in the first 8 weeks
  • Therefore, other secondary and exploratory endpoints were subsequently evaluated, but were not formally tested for statistical significance. These endpoints included:
    • Percent change from baseline in mean cCa during the EAP
    • Percent change from baseline in mean phosphate during the EAP
    • Percent change from baseline in iPTH during the EAP
CI = confidence interval.

In the head-to-head study, patients given Parsabiv® achieved reductions in all 3 key sHPT labs: PTH, phosphorus, and calcium12

Mean iPTH, phosphate, and corrected calcium over time

Parsabiv® + vitamin D and/or phosphate binders*

Sensipar® (cinacalcet) + vitamin D and/or phosphate binders*

*Vitamin D and/or phosphate binders, if prescribed.11

Absolute (mean %) change from baseline

Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.

Given the single, limited-duration (26-week) study design and important study information, these data should not be interpreted as providing evidence of superiority of Parsabiv® to Sensipar®. The potential impact of the difference between treatment groups on clinical outcomes has not been studied, and the clinical meaningfulness of such a difference is unknown.


In the head-to-head study, when initiated at
PTH < 600 pg/mL, 59% of patients given Parsabiv® achieved the study PTH treatment goal13

Subgroup analysis: Patients achieving study iPTH treatment goal during EAP by screening iPTH

Parsabiv® + vitamin D and/or phosphate binders

Sensipar® + vitamin D and/or phosphate binders

*An exploratory efficacy endpoint was the achievement of mean predialysis serum iPTH ≤ 300 pg/mL during the EAP.11
†Vitamin D and/or phosphate binders, if prescribed.11

In an exploratory analysis of the head-to-head study, 38.5% of all Parsabiv® patients achieved iPTH ≤ 300 pg/mL vs 26.2% of all Sensipar® patients during the EAP.

Analysis is exploratory and has not been adjusted for multiple comparisons. No conclusions of statistical or clinical significance can be drawn.

Setting clinical expectations for sHPT patients prescribed Parsabiv®

$name

CLINICAL REFERENCE GUIDE

Important clinical data to share with your colleagues

$name

DOSING & MONITORING

Switching from oral
cinacalcet to Parsabiv®
Coverage icon

REIMBURSEMENT

Parsabiv® reimbursement options are available for patients

Care TEam Corner Icon

CARE TEAM CORNER

Parsabiv® videos and information specifically for dietitians, nurses, and technicians

See More

Important Safety Information for Parsabiv®

Contraindication: Parsabiv® (etelcalcetide) is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including face edema and anaphylactic reaction, 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

Close

Important Safety Information for Parsabiv®

Contraindication: Parsabiv® (etelcalcetide) is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including face edema and anaphylactic reaction, 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.

Please see Parsabiv® full Prescribing Information.

See More

Important Safety Information for Parsabiv® and Sensipar® (cinacalcet)

Contraindications: Parsabiv® (etelcalcetide) is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including face edema and anaphylactic reaction, have occurred.

Sensipar® (cinacalcet) treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range (8.4 mg/dL).

Hypocalcemia: Parsabiv® and Sensipar® lower serum calcium and can lead to hypocalcemia, sometimes severe. Life threatening events

Close

Important Safety Information for Parsabiv® and Sensipar® (cinacalcet)

Contraindications: Parsabiv® (etelcalcetide) is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including face edema and anaphylactic reaction, have occurred.

Sensipar® (cinacalcet) treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range (8.4 mg/dL).

Hypocalcemia: Parsabiv® and Sensipar® lower serum calcium and can lead to hypocalcemia, sometimes severe. Life threatening events and fatal outcomes associated with hypocalcemia have been reported in patients treated with Sensipar®, including pediatric patients. The safety and effectiveness of Sensipar® have not been established in pediatric patients.

Significant lowering of serum calcium can cause QT interval prolongation and ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with Sensipar®. 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® or Sensipar®. Closely monitor corrected serum calcium and QT interval in patients at risk on Parsabiv® or Sensipar®.

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® or Sensipar®. Monitor corrected serum calcium in patients with seizure disorders on Parsabiv® or Sensipar®.

Concurrent administration of Parsabiv® or Sensipar® with calcium-lowering drugs including other calcimimetics could result in severe, life-threatening hypocalcemia. Parsabiv® and Sensipar® should not be given together. Patients switching from Sensipar® to Parsabiv® should discontinue Sensipar® for at least 7 days prior to initiating Parsabiv®. Closely monitor corrected serum calcium in patients receiving Parsabiv® or Sensipar® 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.

Serum calcium and serum phosphorus should be measured within 1 week and PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Sensipar®. Once the maintenance dose has been established, serum calcium and serum phosphorus should be measured approximately monthly, and PTH every 1 to 3 months.

Hypotension, Worsening Heart Failure and/or Arrhythmias: 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.

In Sensipar® postmarketing use, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia were reported in patients with impaired cardiac function. The causal relationship to Sensipar® therapy could not be completely excluded and may be mediated by reductions in serum calcium levels.

Upper Gastrointestinal Bleeding: Cases of gastrointestinal (GI) bleeding, mostly upper GI bleeding, have occurred in patients using calcimimetics, including Sensipar®, from postmarketing and clinical trial sources.

In clinical studies, 2 patients treated with Parsabiv® in 1253 patient years of exposure had upper GI bleeding at the time of death. There were too few cases to determine whether these cases were related to Parsabiv®.

The exact cause of GI bleeding in these patients is unknown. 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® or Sensipar®. Monitor patients for worsening of common Parsabiv® or Sensipar® GI adverse reactions and for signs and symptoms of GI bleeding and ulcerations during Parsabiv® or Sensipar® 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%).

In clinical trials of patients with secondary HPT comparing Sensipar® to placebo, the most commonly reported side effects were nausea (31% vs. 19%), vomiting (27% vs. 15%), and diarrhea (21% vs. 20%).

Indications

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

Sensipar® (cinacalcet) is indicated for the treatment of secondary HPT in adult patients with CKD on dialysis.

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.

Sensipar® is not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia.

Please see Parsabiv® full Prescribing Information and Sensipar® full Prescribing Information.

References: 1. Parsabiv® (etelcalcetide) prescribing information, Amgen. 2. Data on file, Amgen; [Summary of Clinical Efficacy; 2015]. 3. Data on file, Amgen; [Clinical Study Report 20120229; 2014]. 4. Data on file, Amgen; [Clinical Study Report 20120230; 2014]. 5. 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. 6. Data on file, Amgen; [Average Weekly Dose Vitamin D; 2017]. 7. Data on file, Amgen; [Combined Phase 3 Lab Values Multiple Imputation Approach; 2017]. 8. Data on file, Amgen; [Time to First Occurrence of iPTH > 30% Reduction from Baseline-Placebo Studies; 2018]. 9. Data on file, Amgen; [Combined Phase 3 Lab Values Over Time; 2016]. 10. Data on file, Amgen; [Clinical Study Report 20120231; 2015]. 11. 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 trial. JAMA. 2017;317:156-164. 12. Data on file, Amgen; [Clinical Study Report 20120360; 2015]. 13. Data on file, Amgen; [PTH ≤ 300 by Baseline PTH - Study 20120360; 2018]. 14. Data on file, Amgen; [Average weekly calcimimetic dose by iPTH subgroup - Study 20120360; 2019]. 15. Data on file, Amgen; [Vitamin D Dose EAP; 2018].