Fosun Pharma's Novel Calcimimetic Etelcalcetide (Parsabiv®) Approved in China for SHPT in Hemodialysis Patients

On May 6, Fosun Pharmaceutical announced that the new injectable calcimimetic agent Etelcalcetide (trade name: PARSABIV®), for which it has obtained exclusive commercialization rights in collaboration with Amgen, was approved for marketing by the National Medical Products Administration (NMPA). It is indicated for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) undergoing hemodialysis.

SHPT in CKD patients refers to secondary hyperplasia and adenoma formation of the parathyroid tissue, as well as elevated serum parathyroid hormone (PTH) levels, caused by CKD. It is one of the common complications that severely affects the prognosis and quality of life in CKD patients. Patients with SHPT may exhibit clinical symptoms and signs of multi-system damage, such as bone pain, skeletal deformities, fractures, vascular calcification, cardiac calcification, and skin itching, which increase mortality in CKD patients.

It is reported that in 2021, there were 749,000 patients undergoing hemodialysis in China, with an annual growth rate of approximately 10%. Among them, about 60% of the patients suffer from SHPT. The overall compliance rate (according to China’s CKD Mineral and Bone Disorder Diagnosis and Treatment Guidelines: PTH target range is 2-9 times the normal value, approximately 150-600 pg/mL) is only around 50%; if based on the KDOQI guidelines, which specify a PTH target range of 150-300 pg/mL, the compliance rate is less than 34%.

Currently, drugs used to treat SHPT include active vitamin D and its analogs, as well as calcimimetics. However, active vitamin D and its analogs can increase blood calcium and phosphorus levels. Calcimimetics, also known as calcium-sensing receptor (CaSR) agonists, can mimic the action of calcium on tissues by activating CaSR in organ tissues, increasing intracellular calcium, and reducing PTH release. These drugs do not increase intestinal absorption of calcium and phosphorus.1

Etelcalcetide is a novel, long-acting calcimimetic with a half-life of 3 to 4 days and is not metabolized by the cytochrome P450 enzyme system. Phase III studies have confirmed that etelcalcetide effectively reduces parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and bone turnover markers, showing non-inferiority compared to the existing calcimimetic cinacalcet. Subsequent studies further demonstrated the advantages of etelcalcetide in lowering serum PTH levels and achieving PTH target levels.

A network meta-analysis12 found that among all drugs for reducing PTH (etelcalcetide, cinacalcet combined with active vitamin D, cinacalcet, evocalcet, and active vitamin D), etelcalcetide had the highest probability (77.8%) of achieving PTH target levels. In real-world practice, switching from cinacalcet to etelcalcetide can increase the PTH target achievement rate by approximately 30%13-15. Etelcalcetide is administered intravenously three times a week after dialysis, which is better tolerated by patients, reduces the discontinuation rate due to gastrointestinal intolerance16, and improves patient compliance and medication convenience17.

References:

1. Liu Zhihong, Li Guisen. Guidelines for the Diagnosis and Treatment of Mineral and Bone Disorders in Chronic Kidney Disease in China. Beijing: People's Medical Publishing House, 2018.

2. Chen Limeng, Hu Zhao. Clinical Practice of Secondary Hyperparathyroidism in Chronic Kidney Disease [M]. Beijing: People's Medical Publishing House, 2020.

3. Data from the Chinese Blood Purification Case Information Registration System (2021)

4. Yu Xueqing, et al. Chinese Journal of Nephrology, 2018, 34(9):703-708

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11.AngeloKaraboyas,etal.AmJKidneyDis.2022Mar;79(3):362-373

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15.AngeloKaraboyas,etal.AmJKidneyDis.2022Mar;79(3):362-373.

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Editor: Mu Mian

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