Etelcalcetide, an intravenous calcium-sensing receptor agonist, is safe and effective for hemodialysis (HD) patients, according to Japanese researchers.
In a randomized, placebo-controlled, double-blind, phase 3 trial, Masafumi Fukagawa, MD, PhD, of Tokai University School of Medicine in Japan, and collaborators assigned 155 patients with secondary hyperparathyroidism (SHPT) and serum intact parathyroid hormone (iPTH) levels of 300 pg/mL or more to receive etelcalcetide or placebo. Etelcalcetide was given thrice weekly following HD at doses starting at 5 mg, then titrated to 2.5–15 mg every month. Doses of active vitamin D and phosphate binders were kept the same.
After 12 weeks, 59% of etelcalcetide recipients reached target iPTH levels of 60 to 240 pg/mL compared with just 1.3% of those receiving placebo. For 77% of etelcalcetide patients versus 5.2% of placebo users, the drop in iPTH was 30% or more from baseline levels. Serum albumin-corrected calcium, phosphorus, intact fibroblast growth factor-23 (iFGF23) levels, and serum tartrate-resistant acid phosphatase-5b, a marker of bone resorption, also decreased in the etelcalcetide group. Neither pre-treatment with the oral calcimimetic cinacalcet nor baseline iFGF23 levels influenced results, based on subgroup analyses.
No serious adverse events occurred with etelcalcetide. Nausea and vomiting, observed in previous studies of the oral calcimimetic cinacalcet, were mild. Hypocalcemia developed in 1.3% of patients. Fewer than 3% of drug recipients discontinued treatment.
“In conclusion, etelcalcetide is safe, well tolerated and effective in reducing iPTH in Japanese haemodialysis patients with SHPT,” Dr Fukagawa and the team wrote in Nephrology Dialysis Transplantation. “In addition, intravenous etelcalcetide can be easily administered via the blood return after dialysis, thus enabling a decrease in the pill burden on patients, and providing a new alternative for the treatment of SHPT.”
Study funding was provided by Ono Pharmaceutical Co., Ltd, manufacturers of etelcalcetide in Japan.
Fukagawa M, Yokoyama K, Shigematsu T, et al. A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients. Nephrol Dial Transpl, 32:10;1723–1730. doi: 10.1093/ndt/gfw408