赛诺菲（Sanofi）及旗下健赞（Genzyme）8月19日宣布，FDA已批准Cerdelga（eliglustat）胶囊，用作特定1型戈谢病（Gaucher disease）成人患者唯一的一线口服疗法。Cerdelga不适用于经基因检测证实对Cerdelga代谢更快或代谢速度不确定的少数患者。赛诺菲计划在未来一个月内将Cerdelga推向市场。

目前，酶替代疗法（ERT）是戈谢病的标准治疗方案，患者需终身定期（每2周注射一次）接受静脉输注。分析师预计，Cerdelga作为首个口服治疗药物，将完全颠覆当前依赖注射型药物的戈谢病市场格局，成为1型戈谢病群体的一个重要新治疗选择。

赛诺菲花了足足15年时间，终于研制成功首个口服戈谢病药物Cerdelga，该药的临床项目，是有史以来在戈谢病群体中开展的最大规模临床项目，涉及29个国家约400例患者。III期项目中，Cerdelga在2个试验中均成功稳定了病情：其中一项安慰剂对照研究在初治患者中开展，另一项研究则证明了Cerdelga对酶替代疗法Cerezyme的非劣效性。

20多年前，健赞（Genzyme）推出了全球首个戈谢病治疗药物Cerezyme（注射用伊米苷酶，imiglucerase）。过去多年，Cerezyme一直统治戈谢病市场。分析师预计，口服药物Cerdelga将大肆瓜分Cerezyme的市场份额，同时将与另2种注射药物——夏尔（Shire）的Vpriv和辉瑞（Pfizer）的Elelyso展开竞争。据彭博社分析，到2020年，Cerdelga的年销售额将达到7.49亿美元。目前，Cerezyme的年销售额约为9.16亿美元。

Cerezyme曾一度是全球最昂贵的药物，每年的治疗成本高达30万美元。目前，赛诺菲正在考虑如何给Cerdelga定价，可能会跟Cerezyme价格相当。

Cerdelga的获批，对戈谢病群体是一个大好消息，无论从科学和临床角度来看，该药作为一种一线口服药物，已被证明具有积极的风险/利益属性。酶替代疗法（ERT）能够降解沉积在细胞中的脂肪沉积物并会引起各种症状，而Cerdelga则能够直接抑制脂肪沉积物在细胞中的积累。

关于戈谢病（Gaucher disease）：

戈谢病是一种常染色体隐性遗传所造成的葡糖脑苷脂沉积症，主要是因编码葡萄糖脑苷酯酶(gIucocerebrosidase) 的结构基因突变，导致该酶缺乏，致使巨噬细胞内的葡萄糖脑苷脂不能被进一步水解而堆积在溶酶体中，导致细胞失去原有的功能。这些病理性细胞在人体器官中的浸润会造成骨骼、骨髓、脾脏、肝脏和肺部的病变。

目前，全球仅有1万名戈谢病患者，美国患者总数约为6000人。

英文原文：

FDA Approves Genzyme's Cerdelga™ (eliglustat) Capsules

Only First-Line Oral Therapy Approved for the Treatment of
Adults with Gaucher Disease Type 1

CAMBRIDGE, Mass.—Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), announced today that the U.S. Food and Drug Administration (FDA) has approved Cerdelga™ (eliglustat) capsules, the only first-line oral therapy for certain adult Gaucher disease type 1 patients. A small number of adult patients who metabolize Cerdelga more quickly or at an undetermined rate, as detected by an established genetic laboratory test, will not be eligible for Cerdelga treatment. Cerdelga is expected to be available to patients within a month.

"Cerdelga is an important new option for people living with Gaucher disease type 1," said Rhonda Buyers, CEO of the National Gaucher Foundation. "As enzyme replacement therapy is the standard of treatment for Gaucher disease, patients receive regular intravenous infusions for life. With FDA's approval of a first-line oral treatment, Cerdelga has the potential to be a valuable treatment option for people living with this serious disease."

"The approval of Cerdelga is encouraging for Gaucher patients because it is a first-line oral treatment that has demonstrated a positive risk/benefit profile, making it important from both a scientific and a clinical perspective," said Dr. Pramod Mistry, MD, PhD, Professor of Medicine and Pediatrics and the Director of National Gaucher Disease Treatment Center at Yale University School of Medicine. "While enzyme replacement therapies break down fatty deposits that build up in cells and cause a variety of symptoms, Cerdelga inhibits the accumulation of these fatty deposits in the first place."

Genzyme has been researching an oral therapy for Gaucher disease for fifteen years, from early chemistry and preclinical research through clinical development. The Cerdelga clinical development program is the largest ever conducted in Gaucher disease, with approximately 400 patients treated in 29 countries.

"More than twenty years ago, Genzyme introduced the world's first treatment for Gaucher disease. We are proud to build on this legacy and continue to improve Gaucher patients' lives through ongoing research and new therapies," said Genzyme President and CEO, David Meeker, M.D. "The approval of Cerdelga represents our unwavering commitment to the Gaucher patient community."

The FDA approval was based on efficacy data from two positive Phase 3 studies for Cerdelga: one in patients new to therapy (Trial 1), and the other in patients switching from approved enzyme replacement therapies (Trial 2). The filing also incorporated four years of efficacy data from the Cerdelga Phase 2 study.

In Trial 1, improvements were seen across the following endpoints after 9 months on Cerdelga: spleen size, platelet levels, hemoglobin levels, and liver volume. Patients continue to receive Cerdelga in the extension period, and the majority of patients have been on treatment for over eighteen months.

Trial 2 met the pre-specified criteria for non-inferiority to an enzyme replacement therapy (imiglucerase), which was a composite endpoint of each of the following parameters: spleen volume, hemoglobin levels, platelet counts, and liver volume. Patients continue to receive Cerdelga in the extension period, and the majority of patients have been on treatment for over two years.

The most common adverse reactions (≥10%) are fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain.

Cerdelga is a specific ceramide analogue inhibitor of glucosylceramide synthase (IC50 = 10 ng/mL) with broad tissue distribution. It reduces the production of glucosylceramide, the substance that builds up in the cells and tissues of people with Gaucher disease. For more information, visit cerdelga.com.

See full prescribing information for more details about warnings and precautions and a complete list of adverse reactions.

Genzyme's Case Managers provide individualized support services for Gaucher patients, including helping patients identify insurance options; referrals to financial assistance programs; assistance with treatment authorizations if necessary; assistance with appeals; and access to educational resources to help patients learn more about their disease. To reach a local Genzyme Case Manager, call 800-745-4447 (press option #3) Monday through Friday, from 8 a.m. to 6 p.m. ET, or visit our Patient & Caregiver Support Services online portal at www.genzymesupportservices.com.

Marketing applications for Cerdelga are under review by the European Medicines Agency (EMA) and other regulatory authorities.

About Gaucher Disease

Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, β-glucosidase (glucocerebrosidase) that breaks down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. The most common form of Gaucher disease, type 1, generally does not affect the brain.

About Genzyme's Gaucher Disease Program

Driven by a long-term commitment to meeting unmet needs in the Gaucher community, Genzyme has been researching and developing treatments for those living with Gaucher disease for over 20 years. The company's first FDA-approved therapy was the world's first treatment for Gaucher disease. A few years later, Genzyme developed a next-generation enzyme replacement therapy for Gaucher disease, which is now the standard of care with unmatched years of efficacy and safety data. In 2014, Genzyme was the first to bring to market a first-line oral treatment for Gaucher disease, providing a new treatment option for patients. Genzyme will continue to serve this community and remains committed to future advancements.

About Cerdelga

Cerdelga (eliglustat), a novel glucosylceramide analog given orally, was designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease. The concept was initially developed by the late Norman Radin, PhD, from the University of Michigan. In pre-clinical studies, the molecule, developed with James A. Shayman, MD, also from the University of Michigan, showed specificity for glucosylceramide synthase. Following an extensive pre-clinical and early clinical research program, Cerdelga was studied in the largest Phase 3 clinical program ever conducted in Gaucher disease.