Two Phase III trials results for AMG 416 for secondary hyperparathyroidism in CKD patients- Amgen

Amgen has announced pooled data from two pivotal Phase III, global, randomized, placebo-controlled trials evaluating AMG 416, a novel calcimimetic, for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) receiving hemodialysis. Both studies met the primary endpoint, demonstrating that a greater proportion of patients in the AMG 416 groups achieved a greater than 30 percent reduction in parathyroid hormone (PTH) during the Efficacy Assessment Phase compared with placebo. The data were presented today at the 52ndERA-EDTA Congress in London.

In the two Phase III placebo-controlled studies, an aggregate of 1,023 patients with moderate-to-severe SHPT (PTH greater than 400 pg/mL) on hemodialysis were randomized to receive intravenous AMG 416 or placebo three times a week. The primary endpoint of both studies was the proportion of patients achieving greater than 30 percent reduction in PTH during the Efficacy Assessment Phase, defined as weeks 20 through 27. Secondary endpoints included the proportion of patients with PTH less than or equal to 300 pg/mL, and percent reductions in PTH, albumin adjusted calcium (cCa), phosphate (P) and cCa x P. In the AMG 416 group, 74.7 percent of patients achieved a greater than 30 percent reduction from baseline in PTH compared with 8.9 percent in the placebo arm.

Furthermore, a statistically significant proportion of patients (51.5 percent) randomized to receive AMG 416 achieved PTH less than or equal to 300 pg/mL, compared with 5.9 percent in the placebo-controlled group, despite similar baseline mean PTH values of 724 pg/mL and 716 pg/mL, respectively. Significant reductions in phosphate as well as fibroblast growth factor 23 (FGF23) were also observed, with two-thirds of AMG 416-treated patients experiencing a greater than 30 percent reduction in FGF23 concentrations compared with 30 percent of placebo-treated patients.

Comment: SHPT arises when the body attempts to adapt to declining kidney function by increasing production of parathyroid hormone to maintain healthy levels of calcium and phosphorus. Once dialysis kicks in, that excess parathyroid hormone becomes clinically dangerous, and AMG 416 is designed to intervene by interacting with the parathyroid gland.