AMG 416 meets endpoint in Phase III study in hyperparathyroidism in CKD-Amgen

Amgen has announced results from the head-to-head Phase III study comparing AMG 416 with cinacalcet for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) receiving hemodialysis. The study met the primary endpoint of non-inferiority of AMG 416 compared to cinacalcet, measured as the achievement of a greater than 30 percent reduction from baseline in mean pre-dialysis serum intact parathyroid hormone (PTH) levels during the Efficacy Assessment Phase (EAP), defined as the period between weeks 20 and 27.

Further, AMG 416 was statistically significantly superior to cinacalcet in the secondary endpoints of the proportion of patients achieving greater than 50 percent (52.4 percent versus 40.2 percent) and greater than 30 percent (68.2 percent versus 57.7 percent) PTH reduction from baseline during the EAP. There was no difference between the treatment arms in the mean number of days of vomiting or nausea per week in the first eight weeks, another secondary endpoint.

Treatment-emergent adverse events (TEAEs) were reported in 92.9 and 90.0 percent of patients who received AMG 416 and cinacalcet, respectively. TEAEs that were reported in greater than 10 percent of patients in either arm included (AMG 416 versus cinacalcet, respectively): blood calcium decreased (68.9 and 59.8 percent), nausea (18.3 and 22.6 percent), vomiting (13.3 and 13.8 percent) and diarrhea (6.2 and 10.3 percent).

Comment: AMG 416 is a novel calcimimetic agent that is administered intravenously in patients with CKD who are receiving hemodialysis. AMG 416 binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby decreasing serum intact PTH levels. AMG 416 is administered intravenously three times per week during CKD patients' hemodialysis treatments versus the blockbuster Sensipar ( also an Amgen drug), which is an oral calcimimetic taken daily during dialysis. AMG 416 is the planned successor to Sensipar/Mimpara whose patent is due to expire in the US in March 2018.