Etelcalcetide: First Global Approval

@article{Blair2016EtelcalcetideFG,
  title={Etelcalcetide: First Global Approval},
  author={Hannah A. Blair},
  journal={Drugs},
  year={2016},
  volume={76},
  pages={1787-1792}
}
Etelcalcetide (Parsabiv™) is a novel second generation calcimimetic agent developed by Amgen for the treatment of secondary hyperparathyroidism (SHPT), a complication of chronic kidney disease (CKD). Etelcalcetide reduces circulating levels of parathyroid hormone and calcium by binding directly to the calcium-sensing receptor. Intravenous etelcalcetide has been approved in the EU for the treatment of SHPT in adult patients with CKD on haemodialysis therapy. Regulatory applications for… 
Etelcalcetide: A New Intravenous Calcimimetic for the Treatment of Secondary Hyperparathyroidism in Haemodialysis Patients
TLDR
The results of pre-clinical and clinical studies demonstrated that Etelcalcetide decreases effectively PTH levels, which represents a new therapeutic option for the challenging treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD).
New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology
TLDR
A summary of the state of art of CKD-MBD and the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago will be provided.
Old and new calcimimetics for treatment of secondary hyperparathyroidism: impact on biochemical and relevant clinical outcomes
TLDR
Etelcalcetide is a new second-generation calcimimetic with a pharmacokinetic profile that allows thrice-weekly dosing at the time of haemodialysis and is regarded as a second opportunity to improve outcomes by optimizing treatment for SHPT.
Treatment of secondary hyperparathyroidism: the clinical utility of etelcalcetide
TLDR
A new long-acting peptide (etelcalcetide) belonging to the calcimimetics class was approved for intravenous use in hemodialysis patients with SHPT, and was more effective than placebo and cinacalcet, with a PTH reduction of >30% in 76% of patients with etelcalCetide versus 10% with placebo.
New Intravenous Calcimimetic Agents: New Options, New Problems. An Example on How Clinical, Economical and Ethical Considerations Affect Choice of Treatment
TLDR
In a context of person-centered medicine, autonomy, beneficence and non-maleficence should weight more than economic justice in the choice of “economically relevant” drugs.
The Role of the Old and the New Calcimimetic Agents in Chronic Kidney Disease-Mineral and Bone Disorder
TLDR
Etelcalcetide is a new second generation intra-venously administered calcimimetic agent with a pharmacokinetic profile that allows thrice-weekly dosing at the time of hemodialysis and is regarded as a second opportunity to improve outcomes optimizing the treatment for SHPT.
Improved Control of Secondary Hyperparathyroidism in Hemodialysis Patients Switching from Oral Cinacalcet to Intravenous Etelcalcetide, Especially in Nonadherent Patients
TLDR
Etelcalcetide was more effective than cinacalcet in controlling intact parathyroid hormone (iPTH) in this patient population, especially in the nonadherent subgroup, leading to better SHPT control without adverse effects.
Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells
TLDR
This is the first report that etelcalcetide directly reducedParathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism, and Expression levels of the calcium-sensing receptor were significantly lower in primaryhyperparathyroism patient-derived parathyro tissues compared with controls.
Vitamin D and Secondary Hyperparathyroid States.
TLDR
This chapter reviews the current knowledge on the metabolic pathways involved in the vitamin D/PTH axis regulation in different clinical settings and gives an update on the recommended treatment strategies.
...
1
2
...

References

SHOWING 1-10 OF 22 REFERENCES
Treatment of Secondary Hyperparathyroidism: Results of a Phase 2 Trial Evaluating an Intravenous Peptide Agonist of the Calcium-Sensing Receptor
TLDR
AMG416 was well tolerated and appears to be an effective agent for the treatment of SHPT in patients on hemodialysis.
Emerging drugs for secondary hyperparathyroidism
TLDR
This review highlights the pathogenesis of SHPT and current SHPT therapeutic approaches, including the use of low-phosphate diets, phosphate binders, 1,25-dihydroxyvitamin D3 (calcitriol) and its analogs, calcimimetics, and parathyroidectomy, and discusses emerging drugs in development for SHPT.
AMG 416 (velcalcetide) is a novel peptide for the treatment of secondary hyperparathyroidism in a single-dose study in hemodialysis patients.
TLDR
AMG 416 treatment was associated with significant, dose-dependent reductions in serum parathyroid hormone and fibroblast growth factor 23, and all dose groups of 10 mg or more were associated with attenuation in the rise in serum phosphate during the interdialytic period.
The Use of Calcimimetics for the Treatment of Secondary Hyperparathyroidism: A 10 Year Evidence Review
TLDR
Calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathiroidism (PHPT) and parathyroid carcinoma, and underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders.
Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects
  • K. Martin, G. Bell, M. Peacock
  • Medicine, Biology
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2014
TLDR
The results support further evaluation of velcalcetide as a treatment for SHPT in hemodialysis patients with chronic kidney disease—mineral and bone disorder and single IV doses were well tolerated and associated with rapid, sustained, dose-dependent reductions in serum PTH.
Pharmacology of AMG 416 (Velcalcetide), a Novel Peptide Agonist of the Calcium-Sensing Receptor, for the Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients
TLDR
As a long-acting CaSR agonist, AMG 416 is an innovative new therapy for the treatment of hemodialysis patients with secondary hyperparathyroidism and the potential clinical utility of this novel compound is summarized.
Comparison of AMG 416 and cinacalcet in rodent models of uremia
TLDR
As a long-acting CaSR agonist suitable for administration by the IV route, AMG 416 is a potential new therapy for the treatment of CKD patients with SHPT receiving hemodialysis.
Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis
TLDR
Following removal of plasma etelcalcetide by hemodialysis, re-equilibration occurred between SAPC and l-cysteine present in blood to partially restore the etel CALCetide plasma concentrations between dialysis sessions.
A randomized, double-blind, phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients
TLDR
The present clinical findings support the continued development of AMG 416 as a treatment for SHPT in hemodialysis patients and determine a safe and effective starting dose for subsequent phase 2 studies.
...
1
2
3
...