Hyperparathyroidism

June 8, 2015

Amgen reported results of two pivotal phase III, global, randomized, placebo-controlled trials evaluating AMG 416 for 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% reduction in parathyroid hormone (PTH) during the efficacy assessment phase compared with placebo. The two 26-week, double-blind studies enrolled 1,023 patients who received AMG 416 or placebo three times per week by intravenous injection at the end of each hemodialysis treatment. Doses ranged from a minimum of 2.5mg to a maximum of 15mg. The primary endpoint of both studies was the proportion of patients achieving greater than 30% 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 300pg/mL, and percent reductions in PTH, albumin adjusted calcium (cCa), phosphate (P) and cCa x P. In the AMG 416 group, 74.7% of patients achieved a greater than 30% reduction from baseline in PTH compared with 8.9% in the placebo arm. Furthermore, a statistically significant proportion of patients (51.5%) randomized to receive AMG 416 achieved PTH less than or equal to 300pg/mL, compared with 5.9% in the placebo-controlled group, despite similar baseline mean PTH values of 724pg/mL and 716pg/mL, respectively. Significant reductions in phosphate as well as fibroblast growth factor 23 (FGF23) also were observed, with two-thirds of AMG 416-treated patients experiencing a greater than 30% reduction in FGF23 concentrations compared with 30% 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% v. 0.2%, 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.

March 9, 2015

Amgen issued results of a 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 randomized, active-controlled, double-blind, double-dummy study ran over 26 weeks and enrolled 683 patients. 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. The study met the primary endpoint of non-inferiority of AMG 416 compared to cinacalcet, measured as the achievement of a greater than 30% 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% (52.4% v. 40.2%) and greater than 30% (68.2% v. 57.7%) PTH reduction from baseline during the EAP. Treatment-emergent adverse events (TEAEs) were reported in 92.9% and 90% of patients who received AMG 416 and cinacalcet, respectively. Treatment-emergent events related to cardiac failure were reported in 3% of patients who received AMG 416 v. 0.6% in the cinacalcet group. Serious adverse events were reported in 25.1% and 27.3% of patients who received AMG 416 and cinacalcet, respectively. Fatal adverse events were reported in 2.7% for the AMG 416 arm and 1.8% for the cinacalcet arm.

August 25, 2014

Amgen issued results of a second phase III trial of AMG 416 for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). The 26-week, randomized, double-blind, placebo-controlled trial gave subjects AMG 416 or placebo three times per week by intravenous injection with each hemodialysis treatment. Doses ranged from a minimum of 2.5mg to a maximum of 15mg. In the AMG 416 group, 74% of patients achieved a >30% reduction from baseline in PTH compared with 8.3% in the placebo arm, a statistically significant result. Secondary endpoints included the percent change from baseline during the EAP in serum phosphorus (P) concentration (mean changes of -7.71% and -1.31% among patients in the AMG 416 and placebo arms, respectively) and corrected calcium (cCa) concentration (mean changes of -7.29% and 1.18% among patients in the AMG 416 and placebo arms, respectively). Both of these secondary endpoint results were statistically significant. Treatment-emergent adverse events (TEAEs) were reported in 91.6% and 78.7% of patients who received AMG 416 and placebo, respectively. TEAEs that were reported in >10% of patients who received AMG 416 included (AMG 416 v. placebo, respectively): blood calcium decreased (61% and 8.3%), nausea (12.4% and 5.1%), muscle spasms (12% and 7.1%) and vomiting (10.4% and 7.1%).

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