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Etelcalcetide

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Etelcalcetide
Clinical data
Trade namesParsabiv
Other namesVelcalcetide, telcalcetide, AMG-416, KAI-4169, ONO-5163
AHFS/Drugs.comUK Drug Information
License data
Routes of
administration		Intravenous injection
ATC code
Pharmacokinetic data
Elimination half-life3–5 days in dialysis patients
Excretion60% in dialysate, 7% in urine and faeces
Identifiers
  • (6R,9R,12R,15R,18R,21R,24S,29R)-24-Acetamido-1,29-diamino-12,15,18-tris(3-carbamimidamidopropyl)-6-carbamoyl-1-imino-9,21-dimethyl-8,11,14,17,20,23-hexaoxo-26,27-dithia-2,7,10,13,16,19,22-heptaazatria contan-30-oic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC38H73N21O10S2
Molar mass1048.26 g·mol−1
3D model (JSmol)
  • C[C@H](C(=O)N[C@H](CCCNC(=N)N)C(=O)N)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](C)NC(=O)[C@@H](CSSC[C@@H](C(=O)O)N)NC(=O)C
  • InChI=1S/C38H73N21O10S2/c1-18(28(62)56-22(27(40)61)8-4-12-49-35(41)42)53-30(64)23(9-5-13-50-36(43)44)58-32(66)25(11-7-15-52-38(47)48)59-31(65)24(10-6-14-51-37(45)46)57-29(63)19(2)54-33(67)26(55-20(3)60)17-71-70-16-21(39)34(68)69/h18-19,21-26H,4-17,39H2,1-3H3,(H2,40,61)(H,53,64)(H,54,67)(H,55,60)(H,56,62)(H,57,63)(H,58,66)(H,59,65)(H,68,69)(H4,41,42,49)(H4,43,44,50)(H4,45,46,51)(H4,47,48,52)/t18-,19-,21+,22-,23-,24-,25-,26-/m1/s1
  • Key:ANIAZGVDEUQPRI-ZJQCGQFWSA-N

Etelcalcetide (formerly velcalcetide, trade name Parsabiv) is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis. It is administered intravenously at the end of each dialysis session.[1][2] Etelcalcetide functions by binding to and activating the calcium-sensing receptor in the parathyroid gland.[1] Parsabiv is currently owned by AMGEN.[3]

Medical uses

Etelcalcetide is used for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis.[4] Hyperparathyroidism is the condition of elevated parathyroid hormone (PTH) levels and is often observed in patients with CKD.[5]

Contraindications

The drug is of course contraindicated in people with blood serum calcium levels below the norm.[4][6]

Side effects

Common side effects (in more than 10% of people) are nausea, vomiting, diarrhoea, muscle spasms, and hypocalcaemia (too low blood calcium levels). In clinical studies, the latter side effect was usually mild to moderate and without symptoms. An increase of the QT interval of more than 60 ms was detected in 1.2% of people receiving etelcalcetide.[4][6]

Interactions

No interaction studies in humans were conducted. Studies in vitro showed no affinity of etelcalcetide to cytochrome P450 enzymes or common transport proteins. Therefore, no relevant pharmacokinetic interactions are expected.[4][6]

Pharmacology

Mechanism of action

Etelcalcetide functions by binding to and activating the calcium-sensing receptor (CaSR) in the parathyroid gland as an allosteric activator, resulting in PTH reduction and suppression.[1]

Chemistry

The substance is a peptide consisting mostly of D-amino acids instead of the common L-amino acids. More specifically, it is the disulfide of N-acetyl-D-cysteinyl-D-alanyl-D-arginyl-D-arginyl-D-arginyl-D-alanyl-D-argininamide with L-cysteine.[7]

Clinical Trials

In January 2017, AMGEN released a statement concerning the Phase 3 Studies of Parsabiv. Patients using etelcalcetide showed greater symptom reduction compared to the placebo control group. The study also mentioned that further investigation was needed for efficacy and safety confirmation.[8]

In February 2017, a study originally started by KAI Pharmaceuticals showed the Parsabiv was able to elicit a reduction in PTH.[9]

In March 2017, results from a KAI Pharmaceuticals studies showed increase efficacy vs placebo in the reduction in PTH.[10]

History

On 25 August 2015 Amgen Inc. announced its submission of a new drug application to the Food and Drug Administration for etelcalcetide.[1] The European Medicines Agency approved the drug in November 2016.[4]

In February 2017, the FDA approved Parsabiv for the treatment of secondary hyperparathyroidism.[11]

Development

Originally, Etelcalcetide was being developed by KAI Pharmaceuticals. After positive Phase II trials, AMGEN acquired KAI for 315 Million.[12]

Patent Information

Currently, AMGEN is in the application process for a WO Patent for the preparation of Etelcalcetide.[13]

References

  1. ^ a b c d "Amgen Submits New Drug Application For Novel Intravenous Calcimimetic Etelcalcetide (AMG 416)”
  2. ^ Martin, K. J.; Bell, G; Pickthorn, K; Huang, S; Vick, A; Hodsman, P; Peacock, M (2014). "Velcalcetide (AMG 416), a novel peptide agonist of the calcium-sensing receptor, reduces serum parathyroid hormone and FGF23 levels in healthy male subjects". Nephrology Dialysis Transplantation. 29 (2): 385–92. doi:10.1093/ndt/gft417. PMC 3910343. PMID 24235081.
  3. ^ "Parsabiv New FDA Drug Approval | CenterWatch". www.centerwatch.com. Retrieved 2017-10-30.
  4. ^ a b c d e "Parsabiv: EPAR – Product Information" (PDF). European Medicines Agency. 24 November 2016.
  5. ^ Wu, Q; Lai, X; Zhu, Z; Hong, Z; Dong, X; Wang, T; Wang, H; Lou, Z; Lin, Q; Guo, Z; Chai, Y (2015). "Evidence for Chronic Kidney Disease-Mineral and Bone Disorder Associated With Metabolic Pathway Changes". Medicine. 94 (32): e1273. doi:10.1097/MD.0000000000001273. PMC 4616673. PMID 26266360.
  6. ^ a b c Haberfeld, H, ed. (2016). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  7. ^ "Etelcalcetide". ChemSpider. Retrieved 7 January 2016.
  8. ^ Block, Geoffrey A.; Bushinsky, David A.; Cunningham, John; Drueke, Tilman B.; Ketteler, Markus; Kewalramani, Reshma; Martin, Kevin J.; Mix, T. Christian; Moe, Sharon M. (2017-01-10). "Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism". JAMA. 317 (2). doi:10.1001/jama.2016.19456. ISSN 0098-7484.
  9. ^ "Etelcalcetide to Treat Secondary Hyperparathyroidism in Hemodialysis Patients With Chronic Kidney Disease-Mineral and Bone Disorder - Study Results - ClinicalTrials.gov". Retrieved 2017-10-30.
  10. ^ "Safety, Tolerability and Efficacy of Etelcalcetide in Hemodialysis Patients With Secondary Hyperparathyroidism - Study Results - ClinicalTrials.gov". Retrieved 2017-10-30.
  11. ^ "Parsabiv (etelcalcetide) Injection". www.accessdata.fda.gov. Retrieved 2017-10-30.
  12. ^ "Amgen - Investors - Press Release". investors.amgen.com. Retrieved 2017-10-30.
  13. ^ "Espacenet - Bibliographic data". worldwide.espacenet.com. Retrieved 2017-10-30. {{cite web}}: horizontal tab character in |title= at position 13 (help)

Further reading

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