Product Name: Etelcalcetide
Form: Free base
CAS No: 1262780-97-1
Molar Mass: 1048.25
Chemical Formula: C38H73N21O10S2
Synonyms: AMG 416, KAI 4169
Storage: Store at -20℃
Sequence: CARRRAR
Target: CaSR
Application:
Etelcalcetide (CAS: 1262780-97-1) is a synthetic peptide-based calcimimetic drug used in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on dialysis. It functions by mimicking the action of calcium at the calcium-sensing receptors (CaSR) on the parathyroid gland, thereby reducing the secretion of parathyroid hormone (PTH). By lowering PTH levels, etelcalcetide helps to control hypercalcemia, hyperphosphatemia, and bone disorders associated with SHPT. In pharmaceutical chemistry, etelcalcetide's targeted modulation of CaSR represents a significant advancement in the management of CKD-MBD (chronic kidney disease-mineral and bone disorder), addressing a critical aspect of renal disease management and improving patient outcomes. Its application underscores its importance in optimizing mineral metabolism and reducing the risk of complications in CKD patients undergoing dialysis. Additionally, ongoing research explores etelcalcetide's potential in other disorders characterized by dysregulated mineral metabolism, highlighting its versatility in endocrine and metabolic therapeutics.
Current Research:
Etelcalcetide is a synthetic calcium-sensing receptor (CaSR) agonist used primarily in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) undergoing hemodialysis. Secondary hyperparathyroidism is a common complication of CKD, where elevated levels of parathyroid hormone (PTH) can lead to bone and mineral disorders. Etelcalcetide helps to regulate calcium and phosphate balance by reducing PTH secretion, thus improving mineral metabolism and preventing the adverse effects associated with SHPT, such as vascular calcification and bone demineralization. It is administered via intravenous injection during hemodialysis sessions.
Mechanism of Action
Etelcalcetide functions by activating the calcium-sensing receptors (CaSR) located on the parathyroid glands. The CaSR plays a key role in regulating calcium homeostasis by detecting changes in blood calcium levels and modulating PTH secretion in response. When Etelcalcetide binds to the CaSR, it mimics the effect of increased extracellular calcium, leading to a reduction in PTH release. This decreases the levels of circulating PTH, which in turn helps to prevent hyperparathyroidism and its associated complications, including bone demineralization and cardiovascular calcification. The action of Etelcalcetide is more sustained compared to its predecessor, cinacalcet, offering potential clinical advantages in managing SHPT.
Indications and Uses
Etelcalcetide is specifically indicated for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) who are undergoing hemodialysis. SHPT is a common condition in these patients due to impaired kidney function, which disrupts calcium and phosphate balance, leading to elevated PTH levels. By lowering PTH, Etelcalcetide helps to reduce the risks associated with SHPT, such as bone fractures, cardiovascular disease, and renal osteodystrophy. Its use is typically initiated in patients who have not responded adequately to conventional treatments, such as phosphate binders and vitamin D analogs. Etelcalcetide is administered intravenously, typically at the end of a dialysis session.
Efficacy and Clinical Benefits
Clinical studies have shown that Etelcalcetide effectively reduces PTH levels in patients with SHPT, leading to improvements in calcium and phosphate balance. By lowering PTH, Etelcalcetide helps to mitigate the risks of bone and mineral disorders, including vascular calcification and osteitis fibrosa. It has also been demonstrated to reduce the need for other treatments like phosphate binders or vitamin D, as it provides a more direct and effective approach to managing SHPT. Additionally, studies have shown that Etelcalcetide can help to maintain more stable serum calcium levels compared to alternative therapies, such as cinacalcet, which may result in fewer fluctuations in calcium and phosphate metabolism.
Safety and Tolerability
Etelcalcetide is generally well tolerated, but like all medications, it may cause side effects. The most common adverse effects include gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Other side effects can include hypocalcemia (low calcium levels), which can cause muscle cramps, tingling, or more severe symptoms like seizures if not managed appropriately. Hypotension and hyperkalemia are also potential side effects, particularly in patients who are already at risk for electrolyte imbalances due to CKD. Regular monitoring of calcium and phosphate levels is recommended during treatment to avoid complications related to calcium and phosphate dysregulation. Etelcalcetide is contraindicated in patients with hypocalcemia, and care should be taken in patients with a history of seizures.
Advantages and Limitations
The primary advantage of Etelcalcetide over other treatments for SHPT is its ability to reduce PTH levels more effectively and with a longer duration of action compared to cinacalcet. This makes it a useful option for patients who require less frequent dosing or have difficulty adhering to daily oral medications. Additionally, Etelcalcetide’s intravenous administration allows for easier integration into hemodialysis sessions. However, the need for intravenous administration may limit its convenience, especially for patients who do not undergo regular dialysis or those who prefer oral medications. It is also relatively expensive compared to other treatments, which may pose a barrier in certain healthcare settings.
Future Directions
Ongoing research is focused on understanding the long-term effects of Etelcalcetide on patient outcomes, including bone health, cardiovascular events, and mortality in CKD patients with SHPT. Future studies may explore the potential of Etelcalcetide in combination with other therapies, such as phosphate binders or vitamin D analogs, to improve overall mineral metabolism and reduce complications. There is also interest in expanding the use of Etelcalcetide to patients with earlier stages of CKD, before they require hemodialysis, to prevent the progression of SHPT and its associated complications. Additionally, more research is needed to evaluate the cost-effectiveness and overall impact of Etelcalcetide on healthcare systems.
Reference:
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