Promising results of treatment of secondary hyperparathyroidism in chronic kidney diseaseNews - July 21, 2014
A phase III study evaluating AMG 416 (formerly known as velcalcetide) for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis, met its primary and all secondary endpoints.
SHPT is a common, serious and often progressive condition among patients with CKD, affecting many people receiving dialysis. The disorder develops early as an adaptive response to declining kidney function, when the parathyroid gland increase parathyroid hormone (PTH) production in an attempt to maintain normal levels of calcium and phosphorus. Ultimately, the excess PTH production is not sufficient.
AMG 416 is a calcimimetic agent that is administered intravenously in patients with CKD on dialysis. It binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in PTH.
In this 26-week, randomised, double-blind, placebo-controlled study, the primary endpoint was the proportion of patients with >30% reduction in PTH from baseline in the period between weeks 20 and 27 (Efficacy Assessment Phase). 75.3% of patients receiving AMG 416 achieved this, as compared with 9.6% in the placebo arm. Secondary endpoints included the percent change from baseline in serum phosphorus concentration (mean changes of -9.63 vs. -1.60 for patients in the AMG 416 and placebo arm, respectively), as well as corrected calcium concentration (mean changes: -6.69 vs. 0.58 respectively).
515 patients with CKD received AMG 416 or placebo three times a week by intravenous injection, with each haemodialysis treatment. Doses between 2.5 mg to a maximum of 15 mg were used.
Treatment-emergent adverse events (TEAEs) were reported in 91.7 and 81.1% of patients receiving AMG416 and placebo, respectively. TEAEs that were reported in over a tenth of patients on AMG 416, included decreased blood calcium (66.7% vs. 12.0% with placebo), diarrhoea (14.3 vs. 10.0%) and muscle spasms (11.1 vs. 6.2%). Serious adverse events were reported in 24.6% vs. 27.4%, respectively. Vomiting occurred in 7.5 vs. 3.1% of patients in the respective groups, and symptomatic hypocalcaemia was reported in 6.7% vs. none in the placebo group.
"Secondary hyperparathyroidism can be a challenging disease to manage and control. There is an important role for an effective calcimimetic that can be administered intravenously with hemodialysis to help treat this disease," says Sean E. Harper, executive vice president of Research and Development at Amgen.
Press release Amgen 17 July 2014