PCSK9抗体药物在手！辉瑞酝酿开发PCSK9小分子阻断剂药物

关注健康动态的人对低密度脂蛋白（LDL）也许都不陌生，这种脂蛋白能引发人类多种心血管疾病，因此称之为健康杀手也不为过。因此，如何降低人体的LDL水平也已经成为摆在医药开发人员面前的一个重大问题。

研究人员很早就发现，一种名为PCSK9的蛋白在减低LDL水平中具有重要作用。因此，PCSK9也成为一个十分热门的靶点。

目前在这一领域中，辉瑞公司、安进公司以及Regeneron公司和赛诺菲公司都处于领跑位置。不过，最近辉瑞公司表示，公司正在开发一种PCSK9小分子药物阻断剂，预计明年将开展临床研究。在此前的动物实验中，这种药物取得了非常明显的疗效。一些分析人士对这一药物抱以极高的期待。Esperion 公司CEO Tim Mayleben评论说，小分子抑制剂是PCSK9药物中最有发展前景的药物。如果辉瑞公司能够将其变为现实，那么目前现在在研或是已上市的PCSK9抗体药物最终可能都将成为历史。

而另一方面，辉瑞公司在这一领域领跑的PCSK9抗体药物bococizumab已经完成了两项主要的临床研究，并正处于待审批阶段。此外，公司还正在设计一种相关的疫苗药物，患者只需每年接受一次疫苗即可达到长期降低LDL的效果。

与此同时，辉瑞公司的竞争对手们也没有一刻松懈。安进公司作为这一领域的领头羊，正努力推动FDA批准其抗体药物的上市，公司预计FDA将在今年8月27日前做出最终决定，成为这几家公司中最先上市PCSK9抗体药物的公司。而Sanofi和Regeneron也不甘落后，他们付出了6750万美元的代价，促使FDA加速其审批过程，将审批时间由原本的十个月缩短至六个月。

显然，分析人士也对这一领域寄予厚望，预期这些药物的年销售额最高都将达到30亿美元之多。未来这一市场上又是一场龙争虎斗。

详细英文报道：

SAN FRANCISCO--Keeping up the rear in a three-way race to commercialize the first of a new class of anticholesterol antibodies, Pfizer ($PFE) is at work on a pill that attacks the same target, planning to build a franchise in what is expected to be a blockbuster new therapeutic area.

At the JP Morgan Healthcare Conference in San Francisco, Pfizer R&D chief Mikael Dolsten told Reutersthat the company is developing a small-molecule inhibitor of the protein PCSK9, which stands in the way of the body's ability to clear LDL, or "bad," cholesterol from the blood. As it stands, Amgen ($AMGN) and a team of Sanofi ($SNY) and Regeneron ($REGN) lead the race to commercialize injectable therapies that block PCSK9, with Pfizer bringing up the rear with a Phase III program of its own.

The company expects to begin a human trial of its anti-PCSK9 pill later this year, Dolsten told the news service, touting "a substantial reduction" in cholesterol in preclinical animal studies.

Pfizer's antibody, bococizumab, is likely to hit the market after its two main rivals, but Dolsten is taking the long view on PCSK9. Looking beyond first-generation therapies, Pfizer's approach to cholesterol includes the aforementioned pill and an early-stage vaccine candidate--which would block the protein's expression through an annual injection--that could enter Phase I next year.

A pill that inhibits PCSK9 is "a Holy Grail" in the world of lowering LDL cholesterol, according to Esperion ($ESPR) CEO Tim Mayleben, whose company is at work on a small-molecule cardio treatment that taps a different pathway. And if Pfizer can pull off such a feat, its third-place finish in the blockbuster race in PCSK9 antibodies could eventually be lost to history.

Meanwhile, Amgen, long the leader in PCSK9 inhibitors, is expecting to win FDA approval for its treatment no later than Aug. 27. That would have given it months of market exclusivity, but, over the summer, Sanofi and Regeneron paid $67.5 million for an FDA voucher that will cut the review time for their alirocumab down from 10 months to 6 months. Assuming the pair files its drug by year's end as planned, alirocumab will likely be up for approval at the same time if not before Amgen's contender. Further complicating matters, Amgen is suing its rivals over alleged patent infringement.

Analysts figure each PCSK9 antibody will top out at $3 billion a year in sales.