根据赛诺菲（Sanofi）3月7日发布的年度报告，FDA已要求该公司与合作伙伴Regeneron评估实验性胆固醇药物alirocumab对神经认知功能的潜在副作用。预示着新一类降胆固醇药物PCSK9抑制剂研发难度可能加大。
Alirocumab属于名为PCSK9抑制剂的新一类生物技术药物，靶向PCSK9蛋白，该蛋白会增加低密度脂蛋白胆固醇（LDL cholesterol）的生成率，而低密度脂蛋白胆固醇可能阻塞血管，是心脏病的罪魁祸首。
目前，辉瑞和安进开发的PCSK9抑制剂也处于III期阶段。辉瑞在一份电子邮件声明中称：“尚未收到来自FDA的类似要求，在现阶段我们的bococizumab开发项目中，尚不知悉有任何神经认知安全信号。”安进则未立即回应记者的置评请求。
赛诺菲的报告与Regeneron公司上月提交的申请相呼应。上月，FDA已建议Regeneron留意（aware）与PCSK9抑制剂相关的不良认知功能影响。双方称，不知道FDA是如何了解到这一潜在副作用，而他们并不知悉alirocumab有任何类似副作用。
需要注意的是，另一类降胆固醇药物——他汀类药物的使用，已与罕见的问题相关：如记忆力减退、注意力不集中、偏执等。这类药物中，阿斯利康的Crestor和辉瑞的立普妥（Lipitor），是目前最广泛使用的降胆固醇药物，该类药物通过阻断肝脏产生低密度脂蛋白胆固醇发挥作用。
摩根大通分析师Geoff Meacham在一份研究报告中称，尽管我们仍认为PCSK9类药物具有数十亿美元的潜力，但需要指出的是，由于FDA对不良事件猜测的增加，在PCSK9抑制剂类药物获得完全批准前，可能会要求预后数据（outcome data）。而去年FDA曾表示，PCSK9抑制剂类药物可以基于其降低坏胆固醇的能力获得监管批准，并可能不需要证明它们是否能降低心脏发作和中风风险。
如果研究发现神经损伤或其他不良副作用，alirocumab的开发可能会失败或推迟。
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Alirocumab是一种名为PCSK9抑制剂的生物技术类药物。PCSK9抑制剂是一类可自我注射的人造抗体，标靶为一种被称为PCSK9的蛋白，这种蛋白会增加低密度脂蛋白胆固醇的生成率，而低密度脂蛋白胆固醇可以阻塞血管，是心脏病的罪魁祸首。
PCSK9抑制剂提供了一种新的治疗模式，来对抗低密度脂蛋白胆固醇（LDL），被视为自他汀类药物（如Lipitor和Zocor）之后，在对抗心脏疾病中所取得的最大进步。
去年，德意志银行发布报告预测，alirocumab有望成为年销售峰值超过30亿美元的重磅药物。而独立研究机构BioMedTracker预测，到2023年，alirocumab的年销售额将达到37亿美元。
目前，安进（Amgen）、辉瑞（Pfizer）、赛诺菲（Sanofi）及其合作伙伴Regeneron制药、诺华（Novartis）、罗氏（Roche）等制药巨头，正密锣紧鼓地推动PCSK9抑制剂的临床开发。
在这一轮PCSK9抑制剂研发热潮中，安进的AMG145、赛诺菲及Regeneron制药的alirocumab处于领先地位，辉瑞、礼来、诺华、罗氏则处于相对较早的临床开发阶段。
(Reuters) - The Food and Drug Administration has asked Regeneron and Sanofi to assess potential neurocognitive side effects of their experimental cholesterol drug, Sanofi said in its annual report on Friday.
The regulatory filing sent shares of Regeneron down 6 percent in Nasdaq trading. U.S.-listed shares of France-based Sanofi were down 1 percent.
Their drug, alirocumab, is part of a new class known as PCSK9 inhibitors designed to block a protein that maintains "bad" LDL cholesterol in the bloodstream.
Pfizer and Amgen are also in the late stages of developing PCSK9 drugs.
Pfizer said in an emailed statement that it has not received a similar request from the FDA. "At this stage of our bococizumab development program, we are not aware of any neurocognitive safety signals," the company said.
Officials at Amgen did not immediately respond to a request for comment.
Sanofi's report echoed a filing made by Regeneron last month, in which the company said the FDA advised it was aware of adverse neurocognitive effects associated with PCSK9 inhibitors.
The FDA and Regeneron did not immediately respond to requests for comment.
The companies said they did not know how the FDA learned of the potential side effects, and they were not aware of any such side effects with alirocumab.
Rare issues such as memory loss, impaired concentration, and paranoia have been associated with the use of statins for lowering LDL cholesterol.
Statins, such as AstraZeneca's Crestor and generic forms of Pfizer's Lipitor, are the most widely used cholesterol-lowering treatments and work by blocking the liver's production of LDL cholesterol.
"While we continue to believe the PCSK9 class has multi-billion dollar potential, we note that increased speculation on adverse events may increase the probability that the FDA could require outcomes data prior to full approval," JP Morgan analyst Geoff Meacham said in a research note.
The FDA said last year that PCSK9 drugs could get regulatory approval based on their ability to lower bad cholesterol, and may not need to show that they reduce the risk of heart attack and stroke.
In their filings, Sanofi and Regeneron said that if studies detect neurocognitive or other adverse side effects, development of alirocumab could fail or be delayed.
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