Date: 2015-05-29
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 52nd ERA-EDTA Congress in London
Company: Amgen (USA - CA)
Product: AMG 416
Action
mechanism: calcimimetic agent. AMG 416 is a novel calcimimetic agent in Phase 3 clinical development for the treatment of SHPT that is administed intravenously in patients with CKD who are receiving hemodialysis. AMG 416 binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in PTH.
Disease: secondary hyperparathyroidism in patients with chronic kidney disease (CKD) receiving hemodialysis
Therapeutic area: Hormonal diseases - Endocrine diseases - Renal diseases - Kidney diseases
Country: Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Russian Federation, Spain, UK, USA
Trial
details: This study (study number 20120360) was a randomized, active-controlled, double-blind, double-dummy study over 26 weeks that compared the efficacy and safety of AMG 416 with cinacalcet for the treatment of SHPT in 683 patients with CKD receiving hemodialysis. Patients randomized to treatment with AMG 416 received intravenous (IV) doses of AMG 416 three times per week at the end of each dialysis session and daily oral doses of placebo tablets. Subjects randomized to treatment with cinacalcet received daily oral doses of cinacalcet tablets and IV doses of placebo three times per week at the end of each dialysis session. Patients also received standard of care, which could include calcium supplements, vitamin D sterols and phosphate binders, if prescribed by the individual physician. Study 20120229 is designed to assess the efficacy and safety of AMG 416 compared with placebo in the treatment of SHPT in CKD subjects receiving hemodialysis as assessed by the change from baseline in serum iPTH, cCa x P and phosphorus. (NCT01785849)
The primary endpoint was the proportion of patients with greater than 30 percent reduction from baseline in PTH levels during weeks 20 and 27, with the objective of demonstrating non-inferiority of AMG 416 to cinacalcet.
Key and other secondary endpoints included the achievement of a greater than 50 percent reduction from baseline in mean pre-dialysis serum intact PTH during the EAP, achievement of a greater than 30 percent reduction from baseline in mean pre-dialysis serum intact PTH during the EAP, and the mean number of days of vomiting or nausea per week in the first eight weeks. (NCT01788046)
Latest
news: * On May 29, 2015, Amgen announced pooled data from two pivotal Phase 3, 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 at the 52nd ERA-EDTA Congress in London. In the two Phase 3 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. Reductions in serum calcium were observed and symptomatic hypocalcemia occurred more frequently in patients treated with AMG 416 compared to placebo (7.0 percent versus 0.2 percent, respectively). Additional adverse events included muscle spasms and gastrointestinal symptoms (e.g. nausea and vomiting), and they were reported more frequently with AMG 416 compared with placebo. Rates of death, adjudicated major non-fatal cardiovascular events and seizures were similar in both groups. * On February 25, 2015, Amgen announced results from the head-to-head Phase 3 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). TEAEs of hypocalcemia (symptomatic) were reported in 5.0 percent of patients who received AMG 416 versus 2.3 percent in the cinacalcet group. Treatment-emergent events related to cardiac failure were reported in 3.0 percent of patients who received AMG 416 versus 0.6 percent in the cinacalcet group. Serious adverse events were reported in 25.1 and 27.3 percent of patients who received AMG 416 and cinacalcet, respectively. Fatal adverse events were reported in 2.7 percent for the AMG 416 arm and 1.8 percent for the cinacalcet arm.
"These positive pivotal data further underscore the potential of AMG 416 in reducing parathyroid hormone concentrations, and ultimately, in helping treat patients impacted by this challenging disease," said Sean E. Harper , M.D., executive vice president of Research and Development at Amgen . "We are excited to build on our leadership in nephrology and help provide patients with chronic kidney disease on hemodialysis with a new therapeutic option."
