2015年1月12日訊/生物谷BIOON/--近日，賽諾菲和Regeneron Pharmaceuticals宣布，由兩家公司共同研發的alirocumab在最新的臨床試驗中呈陽性結果。該藥物能有效降低高膽固醇血症患者的膽固醇水平，用藥劑量也從一月兩次降至一月一次。
Alirocumab是一種新型注射劑，能夠阻斷一種名為PCSK9的蛋白，這種蛋白會阻止肝臟釋放不良的低密度脂蛋白膽固醇到體內。
PCSK9抑制劑alirocumab在臨床試驗中，用於治療那些對早期治療無反應的患者，他們甚至在服用輝瑞的Lipitor等他汀類藥物後，血液膽固醇含量也都沒有明顯降低。該藥物也同樣適用於那些對其他治療不敏感的患者。
ODYSSEY CHOICE I 和 ODYSSEY CHOICE II這兩次三期臨床試驗主要是為了評估該膽固醇藥物的安全性和有效性。
ODYSSEY CHOICE I試驗中，受試人員為803名高膽固醇血症的患者，他們患心血管疾病的風險由低到高。該試驗為300mg/月alirocumab與安慰劑對照，其中65%以上的患者曾經接受過他汀類藥物治療。
ODYSSEY CHOICE II試驗中，受試人員為233名高膽固醇血症患者，他們都具有極高的患心血管疾病的風險，並且對他汀類藥物不耐受。該試驗為150mg/月alirocumab與安慰劑對照，這組患者此前未接受過他汀類藥物治療。
兩家公司表示，該試驗滿足預設的主要療效指標。該藥物最主要的副作用是頭痛、噁心、上呼吸道感染和疲勞。
此前的研究表明，PCSK9抑制劑可能會提高患者患心臟病的風險，但是alirocumab降低膽固醇的有效性遠遠超過默克的Zetia。試驗表明，那些對他汀類藥物不耐受的高膽固醇血症患者在服用alirocumab後，膽固醇降低的水平超過Zetia十倍之多。
目前，PCSK9抑制劑市場競爭將會非常激烈，與賽諾菲和Regeneron同時競爭的，還有輝瑞和安進，這兩家公司也在抓緊時間讓相關的生物藥上市。如果這類藥物能夠成功地降低由他汀類藥物引發的心臟病發病率和死亡率，日後的銷售額是不言而喻的。目前，安進在同類市場競爭上稍快一籌，2014年8月，安進已向FDA提交了PCSK9抑制劑——evolocumab的審批申請。賽諾菲和Regeneron需要加快節奏，才能贏得先機。
2014年7月，賽諾菲和Regeneron向FDA提供了6750萬美元的保證金，可能有助於加快alirocumab的批准和商業化進程。
據估計，2016年之前，美國和歐盟3600萬人將能購買和使用alirocumab和evolocumab。(生物谷Bioon.com）
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.