Peptide education
Etelcalcetide
Parsabiv · AMG 416
Etelcalcetide is a calcimimetic medicine that lowers parathyroid hormone, or PTH. Parsabiv is used for secondary hyperparathyroidism in adults with chronic kidney disease who receive hemodialysis.
In a 26-week trial, a PTH reduction greater than 30% occurred in 232 of 340 patients assigned etelcalcetide and 198 of 343 assigned cinacalcet. Decreased blood calcium was reported in 68.9% and 59.8%, respectively.
Overview
Quick answer
Secondary hyperparathyroidism in dialysis is different from primary hyperparathyroidism. The Parsabiv label does not recommend it for primary hyperparathyroidism or for chronic kidney disease without hemodialysis.
What does etelcalcetide do?
It activates calcium-sensing receptors on parathyroid cells, reducing PTH secretion. Blood calcium can fall as PTH falls.
Who is Parsabiv for?
The US label covers adults with chronic kidney disease who receive hemodialysis and have secondary hyperparathyroidism.
How is it given?
The label describes an intravenous bolus at the end of hemodialysis, typically three times weekly. Dose changes are guided by PTH and corrected serum calcium.
What is the main safety concern?
Low blood calcium can cause tingling, muscle spasms, seizures, and abnormal heart rhythms. The label calls for calcium testing before treatment and during treatment.
Does a larger PTH reduction prove fewer fractures?
The principal randomized comparisons measured PTH and other biochemical outcomes. They did not establish a reduction in fractures or cardiovascular events.
Evidence
Evidence snapshot
Parsabiv treats secondary hyperparathyroidism in adults with chronic kidney disease receiving hemodialysis.
In two trials, more than 30% PTH reduction was achieved by 74.0% and 75.3% of patients assigned etelcalcetide, versus 8.3% and 9.6% assigned placebo.
Those proportions achieved more than a 30% reduction in PTH with etelcalcetide and cinacalcet, respectively, in a double-blind trial.
The label calls for corrected calcium testing before treatment, after dose changes, and during maintenance.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Etelcalcetide reduces PTH in adults receiving hemodialysis. | Two placebo-controlled trials found greater PTH reduction with etelcalcetide in patients receiving hemodialysis. | The drug activates calcium-sensing receptors on the parathyroid glands. | Supported for the biochemical outcome and dialysis population studied. |
| A larger PTH reduction proves better survival or fewer fractures. | The trials primarily measured biochemical responses over 26 weeks. | The PTH comparison does not establish differences in survival or fractures. | |
| Etelcalcetide has no clinically important effect on calcium. | Decreased blood calcium was more frequent with etelcalcetide than cinacalcet in the active-comparator trial. | The label warns that hypocalcemia can be severe and requires monitoring. |
Bottom line
Main takeaway
This medicine lowers an overactive parathyroid signal in adults on hemodialysis, while calcium levels need close attention.
Treatment is given at the end of hemodialysis and adjusted using both PTH and corrected serum calcium.
The controlled trials compared PTH responses over 26 weeks, not definitive long-term clinical outcomes.
Identity
What it is
Etelcalcetide is a synthetic peptide that activates the calcium-sensing receptor. In chronic kidney disease, secondary hyperparathyroidism involves elevated PTH; Parsabiv is labeled for adults receiving hemodialysis.
Use context
Routes, doses, and cycle patterns
The label describes intravenous treatment at the end of hemodialysis, with PTH and corrected calcium guiding dose changes.
Human studies and product labels
Parsabiv label
- Purpose
- Secondary hyperparathyroidism in adults on hemodialysis
- Context
- US prescribing information
- Route
- Intravenous bolus at the end of hemodialysis
- Amount
- Starting dose 5 mg; maintenance range 2.5 to 15 mg
- Frequency
- Three times weekly
Corrected serum calcium must be at or above the lower limit of normal before starting, increasing, or restarting treatment. The dose is adjusted according to PTH and calcium.
Placebo-controlled trials
- Purpose
- PTH reduction in secondary hyperparathyroidism
- Context
- Two randomized double-blind trials
- Route
- Intravenous at the end of hemodialysis
- Amount
- Started at 5 mg and adjusted up to 15 mg
- Frequency
- Three times weekly
- Duration
- 26 weeks
The primary endpoint was more than a 30% reduction in mean PTH during the assessment period.
Cinacalcet comparison
- Purpose
- Compare PTH responses in patients receiving hemodialysis
- Context
- Randomized double-blind, double-dummy trial
- Route
- Intravenous etelcalcetide or oral cinacalcet
- Amount
- Etelcalcetide started at 5 mg and was titrated between 2.5 and 15 mg; cinacalcet started at 30 mg and was titrated up to 180 mg
- Frequency
- IV study treatment three times weekly; oral study treatment daily
- Duration
- 26 weeks
The trial compared the treatments, rather than giving them together, and assessed PTH response and adverse events including decreased blood calcium.
Research
Research evidence
Placebo-controlled trials and a cinacalcet comparison found PTH reductions in adults with secondary hyperparathyroidism receiving hemodialysis. These trials measured biochemical outcomes over 26 weeks.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Two placebo-controlled trials | 1,023 adults receiving hemodialysis with secondary hyperparathyroidism | Two randomized double-blind trials | Intravenous etelcalcetide versus placebo after dialysis | More than a 30% PTH reduction occurred in 74.0% versus 8.3% in one trial and 75.3% versus 9.6% in the other. | PTH response was a biochemical endpoint; the trials did not establish fracture or survival benefits. | Strong for PTH reduction |
| Etelcalcetide versus cinacalcet | 683 adults on hemodialysis with screening predialysis PTH above 500 pg/mL | Randomized double-blind, double-dummy trial | IV etelcalcetide versus oral cinacalcet | More than a 30% PTH reduction occurred in 232 of 340 patients assigned etelcalcetide versus 198 of 343 assigned cinacalcet. Decreased blood calcium was reported in 68.9% versus 59.8%. | The trial excluded people who had taken cinacalcet within three months before screening. This 26-week comparison does not establish superiority for fractures, cardiovascular events, or survival. | Strong for the measured PTH endpoint |
Cautions
Safety and unknowns
- Severe hypocalcemia can cause muscle spasms, seizures, QT prolongation, and ventricular arrhythmia. The label requires corrected calcium monitoring.
- Parsabiv is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its ingredients. Reactions have included facial swelling and anaphylaxis.
- Concurrent use with an oral calcium-sensing receptor agonist can cause severe, life-threatening hypocalcemia. When switching from cinacalcet, the Parsabiv label specifies stopping cinacalcet for at least seven days and checking that corrected serum calcium is at or above the lower limit of normal before starting.
- The label warns about worsening heart failure and upper gastrointestinal bleeding; the relationships observed in clinical studies were not fully resolved.
- Chronically suppressing PTH may lead to adynamic bone, so PTH also guides dose adjustment.
Mechanism
How it is proposed to work
Etelcalcetide activates the calcium-sensing receptor, signaling the parathyroid glands to release less PTH.
Reduced PTH can lower serum calcium, which explains the label's monitoring and dose-adjustment requirements.
Details
Technical details
Sources
References
- 1.
DailyMed. Parsabiv prescribing information
US indication, dialysis administration, monitoring, and safety warnings.
- 2.
PubMed. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis
doi:10.1001/jama.2016.19456 PMID:28097355
Two randomized placebo-controlled trials of parathyroid hormone reduction.
- 3.
doi:10.1001/jama.2016.19468 PMID:28097356 NCT01896232
Randomized double-blind, double-dummy comparison of parathyroid hormone response and adverse events.
- 4.
European Medicines Agency. Parsabiv European public assessment report
Regulatory assessment describing eligibility and dosing in the active-comparator study.