New FDA approval: parsabiv for hyperparathyroidism

In February 2017, FDA approved Parsabiv intravenous infusion for treatment of hyperparathyroidism in patients undergoing hemodialysis.

End stage kidney disease can cause severe PTH rise, leading to worsening of hyperphosphatemia, higher bone turnover (ex, osteitis fibrosa cystica) and eventually renal osteodystrophy. Secondary kidney-related hyperparathyroidism can increase mortality and morbidity in affected patients.

Parsabiv is supposed to break the cycle of hyperphosphatemia by augmenting the action of calcium thus reducing secretion of PTH by parathyroid chief cells. Results are impressive.

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General Information:

PARSABIV (etelcalcetide) is a calcium-sensing receptor agonist.

Parsabiv is specifically indicated for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis.

Parsabiv is supplied as an injection for intravenous administration. Prior to Parsabiv administration, dose increase, or re-initiation: ensure corrected serum calcium is at or above the lower limit of normal. The recommended starting dose of Parsabiv is 5 mg administered by intravenous (IV) bolus injection three times per week at the end of hemodialysis treatment.

The maintenance dose of Parsabiv is individualized and determined by titration based on parathyroid hormone (PTH) and corrected serum calcium response. The maintenance dose is the dose that maintains PTH levels within the recommended target range and corrected serum calcium within the normal range. The lowest maintenance dose of Parsabiv is 2.5 mg three times per week, and the highest maintenance dose of Parsabiv is 15 mg three times per week.

Administer Parsabiv only at the end of hemodialysis treatment. If a regularly scheduled hemodialysis treatment is missed, do not administer any missed doses. Resume Parsabiv at the end of the next hemodialysis treatment at the prescribed dose. If doses of Parsabiv are missed for more than 2 weeks, re-initiate Parsabiv at the recommended starting dose of 5 mg (or 2.5 mg if that was the patient’s last dose).

 

Clinical Results:

The FDA approval of Parsabiv was based on two 26-week, randomized, double-blind, placebo-controlled studies. An aggregate of 1,023 patients with moderate-to-severe secondary HPT (PTH greater than 400 pg/mL) on hemodialysis were randomized to receive intravenous Parsabiv or placebo three times a week, at the end of their dialysis sessions in addition to standard of care that could include vitamin D and/or phosphate binders.

Primary endpoint of both studies was the proportion of patients achieving greater than 30% reduction from baseline in PTH during the Efficacy Assessment Phase (EAP), defined as weeks 20 through 27.

Secondary endpoints included the proportion of patients with PTH < 300 pg/mL during the EAP; and percent reductions in PTH, albumin-adjusted calcium (cCa), phosphate (P) and cCa x P during the EAP. The two studies showed that significantly more Parsabiv than placebo patients, respectively, achieved:

  • A greater than 30% reduction from baseline in PTH during the EAP: 77% versus 11% in Study 1, and 79% versus 11% in Study 2

  • PTH < 300 pg/mL during the EAP: 52% versus 6% in Study 1, and 56% versus 5% in Study 2

Additionally, greater percent reduction from baseline was achieved in Parsabiv-treated patients than placebo-treated patients during the EAP, for PTH, corrected calcium and phosphate in both studies.

 

Side Effects:

Adverse effects associated with the use of Parsabiv may include, but are not limited to, the following:

  • blood calcium decreased

  • muscle spasms

  • diarrhea

  • nausea

  • vomiting

  • headache

  • paresthesia

 

Mechanism of Action:

Parsabiv (etelcalcetide) is a calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.