安进拟钙剂AMG 416 III期研究达主要及次要终点

安进（Amgen）7月17日公布了实验性药物AMG 416（前身为velcalcetide）一项III期研究（Study 20120230）的积极数据。该项研究是一项为期26周的随机、双盲、安慰剂对照研究，在515例正在接受血液透析治疗的慢性肾脏病（CKD）患者中开展，评估了AMG 416治疗继发性甲状旁腺功能亢进（SHPT）的疗效和安全性。研究中，患者随机接受每周3次静脉注射AMG 416或安慰剂（药物剂量范围为最小2.5mg，最大15mg），同时接受血液透析治疗及标准护理，可能包括：钙补充剂，维生素D固醇和磷酸盐结合剂。数据表明，疗效评估阶段（EAP）（定义为20周-27周），AMG 416治疗组有75.3%的患者实现甲状旁腺激素（PTH）从基线水平下降30%，安慰剂组患者比例为9.6%，数据具有统计学显著差异，达到了研究的主要终点。此外，AMG 416和安慰剂组在次要终点：EAP阶段血清磷（P）水平（AMG 416 vs 安慰剂，-9.63% vs -1.6%）、矫正钙（cCa）水平（-6.69% vs -0.58%）从基线的变化均具有统计学显著差异。这些数据为AMG 416 III期项目的首批数据。

继发性甲状旁腺功能亢进（SHPT，简称继发性甲旁亢），是指在慢性肾功能不全、肠吸收不良综合征、Fanconi综合征和肾小管酸中毒、维生素D缺乏或抵抗以及妊娠、哺乳等情况下，甲状旁腺长期受到低血钙、低血镁或高血磷的刺激而分泌过量的PTH，以提高血钙、血镁和降低血磷的一种慢性代偿性临床表现，长期的甲状旁腺增生最终导致形成功能自主的腺瘤。

AMG 416是一种新颖的拟钙剂（calcimimetic agent），通过静脉给药，目前正处于III期临床开发，用于正在接受血液透析治疗的慢性肾脏病（CKD）患者的治疗。AMG 416结合并激活对甲状旁腺上的钙敏感受体，从而导致实现甲状旁腺激素（PTH）水平的降低。

英文原文：Amgen Announces Positive Phase 3 Results for AMG 416 for the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease Receiving Hemodialysis

Analysis Shows Study Met Primary and All Secondary Endpoints

AMG 416 is a Novel Calcimimetic Administered Intravenously

THOUSAND OAKS, Calif., July 17, 2014 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today 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 percent 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 program.

In the AMG 416 group, 75.3 percent of patients achieved a > 30 percent reduction from baseline in PTH compared with 9.6 percent 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 -9.63 and -1.60 percent among patients in the AMG 416 and placebo arms, respectively) and corrected calcium (cCa) concentration (mean changes of -6.69 and 0.58 percent 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 percent of patients who received AMG 416 and placebo, respectively. TEAEs that were reported in > 10 percent of patients who received AMG 416 included (AMG 416 vs placebo, respectively): blood calcium decreased (66.7 and 12.0 percent), diarrhea (14.3 and 10.0 percent), and muscle spasms (11.1 and 6.2 percent). Serious adverse events (SAEs) were reported in 24.6 and 27.4 percent of patients who received AMG 416 and placebo, respectively. TEAEs of nausea were reported in 9.1 and 7.3 percent of patients who received AMG 416 and placebo, respectively. TEAEs of vomiting were reported in 7.5 and 3.1 percent of patients treated with AMG 416 and placebo, respectively. TEAEs of hypocalcemia (symptomatic) were reported in 6.7 percent of patients who received AMG 416 versus none in the placebo group.

Study Design

This was a 26-week, randomized, 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.

About Secondary Hyperparathyroidism

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.

About AMG 416

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.