Amgen announced that a phase 3 study evaluating AMG 416 (formerly known as velcalcetide) for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD), receiving hemodialysis, met its primary and all secondary endpoints.

The primary endpoint was the proportion of patients with > 30 per cent reduction from baseline in parathyroid hormone (PTH) levels during an Efficacy Assessment Phase (EAP) defined as the period between weeks 20 and 27. Amgen obtained AMG 416 as part of the acquisition of KAI Pharmaceuticals, Inc. in July 2012 and these are the first results to be reported from the Phase 3 programme.

In the AMG 416 group, 75.3 per cent of patients achieved a > 30 per cent reduction from baseline in PTH compared with 9.6 per cent in the placebo arm, a statistically significant result. Secondary endpoints included the per cent change from baseline during the EAP in serum phosphorus (P) concentration (mean changes of -9.63 and 1.60 per cent among patients in the AMG 416 and placebo arms, respectively) and corrected calcium (cCa) concentration (mean changes of -6.69 and 0.58 per cent among patients in the AMG 416 and placebo arms, respectively). Both of these secondary endpoint results were statistically significant.   

"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," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "We are encouraged by the results of this study and look forward to sharing results from a second placebo-controlled study later this year, and a head-to-head study evaluating AMG 416 compared to cinacalcet next year."

Treatment-emergent adverse events (TEAEs) were reported in 91.7 and 81.1 per cent of patients who received AMG 416 and placebo, respectively. TEAEs that were reported in > 10 per cent of patients who received AMG 416 included (AMG 416 vs placebo, respectively): blood calcium decreased (66.7 and 12.0 per cent), diarrhoea (14.3 and 10.0 per cent), and muscle spasms (11.1 and 6.2 per cent). Serious adverse events (SAEs) were reported in 24.6 and 27.4 per cent of patients who received AMG 416 and placebo, respectively. TEAEs of nausea were reported in 9.1 and 7.3 per cent of patients who received AMG 416 and placebo, respectively. TEAEs of vomiting were reported in 7.5 and 3.1 per cent of patients treated with AMG 416 and placebo, respectively. TEAEs of hypocalcemia (symptomatic) were reported in 6.7 per cent of patients who received AMG 416 versus none in the placebo group.

This was a 26-week, randomised, double-blind, placebo-controlled study (study number 20120230) that evaluated the efficacy and safety of AMG 416 for the treatment of SHPT in 515 patients with CKD receiving hemodialysis. Patients received AMG 416 or placebo three times per week by intravenous injection with each hemodialysis treatment. Doses ranged from a minimum of 2.5 mg to a maximum of 15 mg. Patients also received standard of care which could include calcium supplements, vitamin D sterols and phosphate binders, if prescribed by the individual physician.

Secondary endpoints included the proportion of patients with PTH = 300 pg/mL during the EAP and the percent change from baseline during the EAP in values for PTH, serum cCa, corrected calcium-phosphorus product (cCa x P) and P.

Secondary HPT is a common and serious condition that is often progressive among patients with CKD and it affects many of the approximately two million people throughout the world who are receiving dialysis. The disorder develops early as an adaptive response to declining kidney function when the parathyroid glands (four small glands in the neck) increase the production of PTH in an effort to maintain normal levels of calcium and phosphorus. Ultimately, excess PTH production proves inadequate for maintaining normal serum calcium and phosphorous levels. When kidney disease progresses to the point where dialysis is needed to sustain life, SHPT manifests as abnormal PTH, calcium and phosphorus levels that, in turn, can lead to significant clinical consequences.

AMG 416 is a novel calcimimetic agent in Phase 3 clinical development for the treatment of SHPT 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 causing decreases in PTH.

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