Etelcalcetide

Etelcalcetide API 

Etelcalcetide is a novel, synthetic calcimimetic peptide approved for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) receiving hemodialysis. SHPT is a common and serious complication of end-stage renal disease, caused by disruptions in calcium, phosphorus, and vitamin D metabolism. Persistent elevation of parathyroid hormone (PTH) can lead to renal osteodystrophy, vascular calcification, cardiovascular disease, and increased mortality.

Etelcalcetide offers a targeted, non-surgical option to control PTH levels in dialysis patients, representing a second-generation calcimimetic with distinct advantages over oral therapies like cinacalcet.

Mechanism of Action

Etelcalcetide is a synthetic peptide agonist of the calcium-sensing receptor (CaSR), located on the surface of parathyroid gland cells. It mimics the action of extracellular calcium by allosterically activating the CaSR, thereby:

• Suppressing parathyroid hormone (PTH) secretion

• Reducing serum calcium and phosphorus concentrations

• Improving calcium-phosphate homeostasis

• Lowering the risk of bone turnover abnormalities and vascular calcification

Unlike oral calcimimetics, Etelcalcetide is administered intravenously after hemodialysis, which improves treatment adherence and minimizes gastrointestinal side effects.

Clinical Research and Efficacy

Etelcalcetide has been evaluated in multiple Phase 3 clinical trials, including two pivotal randomized controlled studies published in The Lancet and New England Journal of Medicine. These studies involved over 1000 hemodialysis patients with uncontrolled SHPT.

Key clinical outcomes include:

• Statistically significant reductions in PTH levels (>30% in a majority of patients)

• Superior control of serum phosphorus and calcium-phosphate product (Ca × P)

• Greater overall biochemical response rates compared to cinacalcet

• Better patient adherence due to thrice-weekly post-dialysis IV administration

• Reduction in bone turnover markers (e.g., bone-specific alkaline phosphatase)

These benefits support Etelcalcetide as a first-line injectable calcimimetic for managing SHPT in dialysis patients.

API Manufacturing and Quality

Our Etelcalcetide API is manufactured via solid-phase peptide synthesis (SPPS), ensuring high yield, purity, and molecular stability. The API:

• Conforms to stringent GMP and ICH Q7 standards

• Is suitable for use in injectable drug products

• Undergoes comprehensive analytical testing, including HPLC, residual solvents, heavy metals, and endotoxin levels

• Is available in pilot and commercial production scales

Therapeutic Potential and Advantages

• Non-hormonal treatment for SHPT in CKD patients on dialysis

• IV route ensures compliance, particularly in patients with pill burden or GI intolerance

• May help reduce long-term complications of mineral and bone disorder (CKD-MBD)

• Compatible with phosphate binders, vitamin D analogs, and standard dialysis care