2015年1月12日讯/生物谷BIOON/--近日，赛诺菲和Regeneron Pharmaceuticals宣布，由两家公司共同研发的alirocumab在最新的临床试验中呈阳性结果。该药物能有效降低高胆固醇血症患者的胆固醇水平，用药剂量也从一月两次降至一月一次。
Alirocumab是一种新型注射剂，能够阻断一种名为PCSK9的蛋白，这种蛋白会阻止肝脏释放不良的低密度脂蛋白胆固醇到体内。
PCSK9抑制剂alirocumab在临床试验中，用于治疗那些对早期治疗无反应的患者，他们甚至在服用辉瑞的Lipitor等他汀类药物后，血液胆固醇含量也都没有明显降低。该药物也同样适用于那些对其他治疗不敏感的患者。
ODYSSEY CHOICE I 和 ODYSSEY CHOICE II这两次三期临床试验主要是为了评估该胆固醇药物的安全性和有效性。
ODYSSEY CHOICE I试验中，受试人员为803名高胆固醇血症的患者，他们患心血管疾病的风险由低到高。该试验为300mg/月alirocumab与安慰剂对照，其中65%以上的患者曾经接受过他汀类药物治疗。
ODYSSEY CHOICE II试验中，受试人员为233名高胆固醇血症患者，他们都具有极高的患心血管疾病的风险，并且对他汀类药物不耐受。该试验为150mg/月alirocumab与安慰剂对照，这组患者此前未接受过他汀类药物治疗。
两家公司表示，该试验满足预设的主要疗效指标。该药物最主要的副作用是头痛、恶心、上呼吸道感染和疲劳。
此前的研究表明，PCSK9抑制剂可能会提高患者患心脏病的风险，但是alirocumab降低胆固醇的有效性远远超过默克的Zetia。试验表明，那些对他汀类药物不耐受的高胆固醇血症患者在服用alirocumab后，胆固醇降低的水平超过Zetia十倍之多。
目前，PCSK9抑制剂市场竞争将会非常激烈，与赛诺菲和Regeneron同时竞争的，还有辉瑞和安进，这两家公司也在抓紧时间让相关的生物药上市。如果这类药物能够成功地降低由他汀类药物引发的心脏病发病率和死亡率，日后的销售额是不言而喻的。目前，安进在同类市场竞争上稍快一筹，2014年8月，安进已向FDA提交了PCSK9抑制剂——evolocumab的审批申请。赛诺菲和Regeneron需要加快节奏，才能赢得先机。
2014年7月，赛诺菲和Regeneron向FDA提供了6750万美元的保证金，可能有助于加快alirocumab的批准和商业化进程。
据估计，2016年之前，美国和欧盟3600万人将能购买和使用alirocumab和evolocumab。
原文 Sanofi (SNY)， Regeneron Pharmaceuticals Cholesterol Drug Effective In Once-Monthly Doses
Sanofi SA (ADR) (NYSE：SNY) and Regeneron Pharmaceuticals Inc (NASDAQ：REGN) announced that clinical trials to examine alirocumab， a drug developed by both companies， showed positive topline results. The drug was effective in reducing bad cholesterol levels in hypercholesterolemia patients， even at a once-monthly dose instead of a twice-monthly one.
The injectable drug is among the new class of treatment for cholesterol， and works by blocking PCSK9， a naturally occurring protein that keeps the liver from releasing bad LDL cholesterol in the body.
PCSK9 inhibitors are used to treat patients who have not responded to earlier treatments， and whose cholesterol levels did not drop significantly， even after being administered with statins such as Pfizer Inc.’s (NYSE：PFE) Lipitor. The inhibitors are also aimed at patients who cannot tolerate other treatments.
Two Phase-III trials， ODYSSEY CHOICE I and ODYSSEY CHOICE II， were conducted to evaluate the safety and efficacy profiles of the cholesterol drug.
The first trial enrolled 803 hypercholesterolemia patients at moderate to high cardiovascular (CV) risk. The study compared a 300 mg once-monthly dose to a placebo. Over 65% of the enrolled subjects received statin therapy as well.
The second trial had 233 hypercholesterolemia patients at high cardiovascular risk， and who had not been able to tolerate 2 or more statins. The study compared a 150 mg once-monthly dose to a placebo. This group did not receive any statin therapy.
The company announced that both trials “met their primary efficacy points”. The most common side effects observed during the studies were headache， nausea， upper respiratory tract infection， and fatigue.
The results from earlier studies indicated that the PCSK9 inhibitor could pose heart risk to patients. On the other hand， one of the studies showed alirocumab to be significantly more effective in lowering bad cholesterol levels than Merck & Co.， Inc.’s (NYSE：MRK) Zetia. The number of high-risk statin-intolerant patients who got their cholesterol levels reduced by alirocumab was 10 times higher than those who took Zetia.
Companies are getting into highly competitive wars for the development and commercialization of PCSK9 inhibitors， with each one trying to get its own inhibiting candidate out in the market before rivals. Sanofi and Regeneron are racing with Amgen， Inc. (NASDAQ：AMGN) and Pfizer to introduce these biotech drugs. If these drugs succeed in reducing heart attacks and mortality rates caused by statins， they can be expected to generate billions of dollars. Amgen currently has a head start in the commercialization of its drug， since it filed the application for its inhibitor， evolocumab， with the US Food and Drug Administration (FDA) in August 2014.
In July 2014， Sanofi and Regeneron bought a $67.5 million voucher that could help speed up the approval and commercialization process for alirocumab.
Roth Capital's Joseph Pantginis has estimated that as many as 36 million people in the US and the EU will be eligible for alirocumab and evolocumab by 2016.