What Is Etelcalcetide (Parsabiv)? The Calcimimetic Peptide for Secondary Hyperparathyroidism on Dialysis and What Its Trials Found

Etelcalcetide, sold as Parsabiv, is a synthetic peptide that lowers parathyroid hormone (PTH) in adults with chronic kidney disease who are on hemodialysis. The [FDA label on DailyMed](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd270093-c6a8-4596-a4ab-e6aa0a2c8a0c) lists an initial U.S. approval in 2017 and a single indication, which is secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis. You would never take etelcalcetide at home, because it is given as an intravenous injection at the end of each dialysis session, so there is no daily pill for anyone to remember.

Etelcalcetide is worth knowing for a second reason, which is that it was the first calcimimetic built as a peptide, and it is made mostly from D amino acids, the mirror image of the amino acids your body normally uses. That design is one reason the drug lasts for days in the blood of people whose kidneys no longer clear medicines. This article covers what secondary hyperparathyroidism is, how etelcalcetide works, what its phase 3 trials against placebo and against cinacalcet found, how it is dosed and what the label says about side effects. It is educational content about published research, not medical advice.

Secondary hyperparathyroidism is a condition in which the parathyroid glands make too much PTH because the kidneys can no longer keep calcium, phosphate and vitamin D in balance. The parathyroid glands themselves are not diseased at the start, which is what makes the condition secondary, since they are responding to signals from failing kidneys. Over time the glands enlarge and keep secreting PTH even when they should stop.

The investigators of the head to head trial ([Block, JAMA, 2017](https://doi.org/10.1001/jama.2016.19468)) note that secondary hyperparathyroidism contributes to calcification outside the skeleton and is associated with higher overall and cardiovascular mortality, and that control is suboptimal in the majority of patients on hemodialysis. High PTH pulls calcium out of bone, which weakens the skeleton, and the calcium and phosphate released can settle in blood vessels and soft tissue.

Standard treatment in dialysis units includes phosphate binders, active vitamin D drugs and calcimimetics, and surgery to remove parathyroid tissue is an option when medicines fail. Etelcalcetide belongs to the calcimimetic group. For background on how PTH works as a hormone, see our guide to [palopegteriparatide (Yorvipath)](/articles/palopegteriparatide-yorvipath-hypoparathyroidism), which covers the opposite problem of too little PTH.

Etelcalcetide works by making the calcium sensing receptor on parathyroid cells more responsive to calcium, so the glands behave as though blood calcium is higher than it really is and release less PTH. The Parsabiv label says etelcalcetide "binds to the CaSR and enhances activation of the receptor by extracellular calcium," and that activation of the receptor on parathyroid chief cells decreases PTH secretion.

Drugs that work this way are called calcimimetics because they mimic the effect of calcium on that receptor, and the effect of etelcalcetide arrives quickly. According to the label, PTH levels decreased within 30 minutes after a single intravenous dose, and the size and length of the drop increased with the dose.

Etelcalcetide is a short synthetic peptide, and the label describes it as a chain of D amino acids, mostly D arginine, with an extra L cysteine attached through a disulfide bond and a molecular weight of 1047.5 g/mol. The label calls Parsabiv a synthetic peptide agonist of the calcium sensing receptor, which places it in the same family of engineered therapeutic peptides as many of the drugs covered on this site.

The D amino acid backbone matters because the enzymes that break down ordinary peptides are built to recognize L amino acids. Instead of being chopped up, etelcalcetide is transformed in the blood by disulfide exchange, mostly forming conjugates with serum albumin. The label states that etelcalcetide is not metabolized by CYP450 liver enzymes, which closes off one common route for drug interactions. Our article on [peptide half life and dosing frequency](/articles/peptide-half-life-dosing-frequency) explains why structural choices like these shape how often a peptide is given.

Etelcalcetide stays in the body for days in people on hemodialysis. The label reports an effective half life of 3 to 4 days, with steady state reached in 7 to 8 weeks and a predicted accumulation of 3 to 4 fold, and that long half life is what allows a dose only three times a week, matched to the usual dialysis schedule.

The two phase 3 placebo controlled trials found that etelcalcetide cut PTH by more than 30% in about three out of four patients, compared with fewer than one in ten on placebo. Block and colleagues reported both trials together in JAMA in 2017 ([Block et al., JAMA, 2017](https://doi.org/10.1001/jama.2016.19456)).

The trials enrolled 1023 patients on hemodialysis with moderate to severe secondary hyperparathyroidism, with 508 in trial A and 515 in trial B. Patients received intravenous etelcalcetide or placebo after each dialysis session for 26 weeks, and their mean age was 58.2 years.

PTH roughly halved on etelcalcetide, while PTH on placebo drifted upward, which shows how steadily the condition progresses without treatment. About half of the treated patients also reached a PTH of 300 pg/mL or lower, compared with about one in twenty on placebo.

The trials also recorded side effects. In trials A and B, muscle spasms affected 12.0% and 11.1% of people on etelcalcetide versus 7.1% and 6.2% on placebo, nausea affected 12.4% and 9.1% versus 5.1% and 7.3%, and vomiting affected 10.4% and 7.5% versus 7.1% and 3.1%.

A separate phase 3 trial in Japan pointed the same way. Fukagawa and colleagues ([Nephrology Dialysis Transplantation, 2017](https://doi.org/10.1093/ndt/gfw408)) randomized 155 Japanese hemodialysis patients to etelcalcetide or placebo for 12 weeks, with the primary endpoint set as reaching the Japanese target range for intact PTH of 60 to 240 pg/mL. That target was met by 59.0% of patients on etelcalcetide versus 1.3% on placebo, and a reduction of 30% or more was reached by 76.9% versus 5.2%.

On PTH lowering, etelcalcetide beat oral cinacalcet in the only large head to head trial, although it also lowered blood calcium more often. Cinacalcet is an oral calcimimetic taken daily, and it was the standard calcimimetic before etelcalcetide arrived.

Block and colleagues ran a double blind, double dummy trial in 683 hemodialysis patients with PTH higher than 500 pg/mL at 164 sites ([Block et al., JAMA, 2017](https://doi.org/10.1001/jama.2016.19468)). Each patient received one active drug and a matching placebo for the other, so 340 patients got IV etelcalcetide with an oral placebo and 343 got oral cinacalcet with an IV placebo, for 26 weeks.

Etelcalcetide met the noninferiority goal and then met the criteria for superiority. The authors had hoped an IV drug given in the dialysis unit might also improve adherence and reduce stomach side effects, since a nurse gives every dose. The abstract reports the most common adverse effect as decreased blood calcium, and the authors concluded that further studies are needed on clinical outcomes and on longer term efficacy and safety.

A network meta analysis by Palmer and colleagues ([American Journal of Kidney Diseases, 2020](https://doi.org/10.1053/j.ajkd.2020.02.439)) pooled 36 trials with 11,247 participants, with a median follow up of 26 weeks. Etelcalcetide had the highest odds of reaching a PTH target compared with cinacalcet (odds ratio 2.78) and evocalcet (odds ratio 4.93), and it also appeared to cause more hypocalcemia than either.

The more important finding concerned what the evidence cannot show. The authors concluded that the evidence of benefit for calcimimetics rests on short term changes in serum PTH, which is a surrogate marker rather than a health outcome. Differences in death, cardiovascular events or fractures could not be discerned with sufficient certainty, and the review could not name one preferred agent.

Etelcalcetide is dosed by the dialysis team rather than by the patient. The label sets a starting dose of 5 mg by intravenous bolus three times per week at the end of hemodialysis, and the maintenance dose is adjusted to PTH and calcium within a range of 2.5 to 15 mg three times per week.

The label also requires that a patient switching from cinacalcet stop cinacalcet for at least 7 days and then start etelcalcetide at 5 mg, because combining two calcimimetics can cause severe, life threatening hypocalcemia.

The main risk of etelcalcetide is low blood calcium, and the label also warns about heart failure, gastrointestinal bleeding and oversuppressed bone. These warnings follow directly from how the drug works, since lowering PTH also lowers calcium.

Hypocalcemia. The label warns that severe hypocalcemia can cause paresthesias, muscle spasms, seizures, QT prolongation and ventricular arrhythmias, so people prone to QT prolongation or seizures need closer monitoring.

Worsening heart failure. In clinical studies, heart failure requiring hospitalization occurred in 2% of people on Parsabiv and 1% on placebo, and the label says a causal link could not be completely excluded.

Upper gastrointestinal bleeding. Two patients treated with Parsabiv over 1253 patient years of exposure had upper GI bleeding noted at the time of death, compared with none over 384 patient years in the control groups, so patients with risk factors for GI bleeding may be at higher risk.

Adynamic bone. If PTH is pushed too low for too long, bone turnover can slow too much, and the label calls for reducing or stopping the dose if PTH falls below the target range.

The label also lists hypersensitivity reactions and advises that Parsabiv is not recommended during breastfeeding. Our overview of [difelikefalin (Korsuva)](/articles/difelikefalin-korsuva-kappa-opioid-peptide-dialysis-itch) covers another peptide drug that is given the same way, through the dialysis line.

Longer term studies suggest the PTH effect of etelcalcetide lasts at least a year, but those studies are small or uncontrolled, so they cannot prove clinical benefit.

In the one year open label extension ([Bushinsky et al., Nephrology Dialysis Transplantation, 2020](https://doi.org/10.1093/ndt/gfz039)), approximately 68% of patients kept a PTH reduction of more than 30% and about 56% reached a PTH of 300 pg/mL or lower, while decreased blood calcium was reported in 43.3% and symptomatic hypocalcemia occurred in 3.7%. The study had no placebo group.

The VICTORY trial in Japan ([Shoji et al., Clinical Journal of the American Society of Nephrology, 2021](https://doi.org/10.2215/CJN.16601020)) randomized 326 patients to etelcalcetide 5 mg three times weekly or the vitamin D drug maxacalcitol for 12 months. Its outcome was T50, a lab test of how readily blood forms calcium crystals in which a longer time is better. The median T50 rose from 123 to 166 minutes on etelcalcetide and from 116 to 131 minutes on maxacalcitol, a difference in change of 20 minutes, but T50 is a surrogate marker and there was no difference in grip strength or cognition.

A small single arm bone study ([Khairallah et al., Clinical Journal of the American Society of Nephrology, 2023](https://doi.org/10.2215/CJN.0000000000000254)) enrolled 22 hemodialysis patients, of whom 13 completed 36 weeks of etelcalcetide. PTH declined 67%, femoral neck bone mineral density rose 7%, spine and total hip density rose 3% and spine trabecular bone score rose 10%, but with so few completers and no control group the study can only generate hypotheses. For the wider topic of peptides and bone, see our comparison of [teriparatide and abaloparatide](/articles/teriparatide-abaloparatide-bone-building-peptides).

Etelcalcetide is only for adults with chronic kidney disease who are on hemodialysis. The label states that it has not been studied in parathyroid carcinoma, primary hyperparathyroidism or chronic kidney disease not on hemodialysis, and that it is not recommended in those groups. Etelcalcetide is a prescription drug given by a dialysis unit rather than a research peptide, and there is no evidence base for any use outside that setting.

Etelcalcetide is a well studied peptide drug with a narrow purpose. In trials lasting 26 weeks it lowered PTH far more than placebo and more than cinacalcet, and an IV dose given by the dialysis team removes the adherence problem of a daily pill. The trade off is more low blood calcium, which is why calcium is checked within 1 week of every dose change. What the trials have not shown is whether lower PTH on etelcalcetide translates into fewer fractures, heart events or deaths, and that question remains open, so if you or someone you care for is on dialysis, the right person to weigh these trade offs is your nephrologist and dialysis care team.