3月29日，安进在美国心脏病学会(ACC)年会上发布了3期临床研究GAUSS-2和LAPLACE-2的详细结果，结果显示其试验药物PCSK9抑制剂Evolocumab可明显降低他汀耐受患者的低密度脂蛋白胆固醇(LDL)水平。

安进负责研发的执行副总裁Sean Harper指出，这些结果“为我们提供了重要的见解，Evolocumab作为一款治疗药物可能会用于一系列处于心血管疾病风险的患者。”

GAUSS-2研究结果同时发布在了NEJM上，这项研究由307名他汀耐受的高胆固醇患者参与。患者被随机分成四组，接受安慰剂、默沙东的依泽替米贝，或皮下注射Evolocumab进行治疗，Evolocumab也称AMG 145，每两周用药一次，或每月使用一次最高剂量。

试验的共同终点是第12周时，LDL胆固醇相较基线值的下降百分数，及在10周和第12周时LDL胆固醇相较基线值下降的平均百分数。结果显示，Evolocumab治疗组相比依泽替米贝治疗组，LDL胆固醇平均下降值在37%至39%之间。

LAPLACE-2研究招募了1896名原发性高胆固醇血症及混合型血脂异常患者。安进报道说，Evolocumab（每两周用药一次，或每月一次最高剂量）与每天不同剂量他汀类药物合并用药，与安慰剂相比，LDL胆固醇从基线值平均下降55%至76%，与依泽替米贝相比，LDL胆固醇从基线值平均下降33%至47%。

在ACC会议上报道的其它3期试验结果中，周期为52周的DESCARTES试验由901名患有高脂血症及一系列心血管风险的患者参与，试验数据显示，Evolocumab用于有降脂治疗背景的患者，与安慰剂相比，LDL胆固醇平均下降57%。

该公司进一步指出，MENDEL-2试验由614名未使用他汀类药物的患者参与，试验数据证实，使用Evolocumab治疗三个月后，与安慰剂相比，LDL胆固醇下降55%至57%，与依泽替米贝相比，LDL胆固醇下降38%至40%。
 

RUTHERFORD-2研究由329名杂合型家族性高胆固醇血症患者参与，试验数据显示，这款PCSK9抑制剂使LDL胆固醇下降59%至66%。

Harper表示，安进 “就这款药物的全球上市申报正与监管当局密切合作，希望将这一新的治疗选择带给血脂异常患者。”该公司指出，今年将向美国提交Evolocumab的上市申请。这款药物预期与辉瑞处于后期试验的同类候选药物进行竞争。此外竞争者还有来自赛诺菲及其合作伙伴再生元的一款药物。

分析师已预测，如果获得批准，假定保险公司同意为这些药物支付，那每款药物可能会产生至少30亿美元的年销售额。一些分析师认为，这些产品的成本要远远超过他汀类药物。

三月初，FDA要求赛诺菲与再生元确定，在他们的PCSK9抑制剂试验药物Airocuma全球开发项目的试验是否有神经认知不良事件发生，特别是在长期研究中。安进全球开发执行医学总监Scott Wasserman评论说，我们已非常非常仔细地检查了我们的数据，并将联合FDA继续仔细检查。我们尚未发现与Evolocumab与神经认知安全性有关。
 

Amgen presents additional positive Phase III results for PCSK9 inhibitor evolocumab

Amgen said Sunday that it presented detailed Phase III findings at the American College of Cardiology (ACC) scientific meeting from the previously announced GAUSS-2 and LAPLACE-2 studies showing that its experimental PCSK9 inhibitor evolocumab significantly reduced low-density lipoprotein (LDL) cholesterol in patients with statin intolerance, and when it was tested among other patients in combination with statin therapy. Sean Harper, executive vice president of R&D at Amgen, noted that the results, as well as those from three other late-stage evolocumab trials presented during the conference, "provide us with imp0rtant insights on the potential of [the drug] as a treatment for a range of patients at-risk for cardiovascular disease."

The GAUSS-2 study, whose results were simultaneously published in the NEJM, involved 307 patients with high cholesterol who were unable to tolerate effective doses of at least two different statins due to muscle-related side effects. Patients were randomised to four treatment arms, receiving placebo, Merck & Co.'s Zetia (ezetimibe), or subcutaneous evolocumab, also known as AMG 145, which was administered either every two weeks or at a higher dose on a monthly basis. The co-primary endpoints were the percent reduction from baseline in LDL cholesterol at week 12 and the mean percent reduction from baseline in LDL cholesterol at weeks 10 and 12. Results showed that treatment with evolocumab reduced mean LDL cholesterol by between 37 percent and 39 percent, compared with Zetia.

The LAPLACE-2 study enrolled 1896 patients with primary hypercholesterolaemia and mixed dyslipidaemia who had initially been randomised to one of five background statin treatments, including varying doses of atorvastatin, rosuvastatin, and simvastatin. Patients were subsequently assigned to different treatment groups that included subcutaneous evolocumab, Zetia or placebo. Amgen reported that evolocumab, administered once every two weeks or at a higher dose monthly, in combination with different daily doses of statin therapy reduced mean LDL cholesterol by 55 percent to 76 percent from baseline versus placebo, and from 38 percent to 47 percent from baseline compared to Zetia.

In other Phase III results reported at the ACC meeting, Amgen said that data from the 52-week DESCARTES trial of 901 patients with hyperlipidaemia and a range of cardiovascular risk showed that evolocumab, given in combination with background lipid-lowering therapy, on average lowered LDL cholesterol by 57 percent versus placebo. The company further noted that data from the MENDEL-2 trial, which enrolled 614 hyperlipidaemic patients who were not receiving statins, demonstrated that three months of evolocumab cut LDL cholesterol by 55 percent to 57 percent versus placebo, and by 38 percent to 40 percent more than Zetia. Meanwhile, data from the RUTHERFORD-2 study of 329 patients with heterozygous familial hypercholesterolaemia, who received one of two doses of subcutaneous evolocumab or placebo, showed that the PCSK9 inhibitor reduced LDL cholesterol by 59 percent to 66 percent.

Harper said Amgen is "working closely with regulatory authorities on our global filing plan in hopes of bringing this new treatment option to patients with dyslipidaemia." The company indicated it will file its application seeking US approval of evolocumab sometime this year. The drug is expected to compete with similar late-stage drug candidates from Pfizer, as well as one stemming from a partnership between Sanofi and Regeneron Pharmaceuticals. Analysts have estimated that each of the drugs could generate annual sales of at least $3 billion, if approved, assuming insurers agree to cover them. Some analysts expect the products to cost far more than statins.

Earlier this month, the FDA asked Sanofi and Regeneron to determine whether any neurocognitive adverse events occurred in any trials of the global development programme for their experimental PCSK9 inhibitor alirocuma, particularly in longer-term studies. Scott Wasserman, Amgen's executive medical director for global development, remarked that "we've looked at our data very, very carefully and are continuing to look at it very carefully in combination with the FDA. We haven't seen any (neurocognitive) safety signals" with evolocumab.

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