近日，美国食品和药物管理局（FDA）已批准Zeposia（ozanimod）上市，用于治疗成人复发型多发性硬化症（RMS），包括临床孤立综合征、复发缓解性疾病、活动性继发进展性疾病。
Zeposia是一种口服药物，每天服用一次，该药是唯一被批准具有以下特征的鞘氨醇-1-磷酸（S1P）受体调节剂：在RMS患者启动治疗时，无需进行基因测试、无需基于标签的首次剂量观察。由于可能发生心率短暂下降和房室传导延迟，因此应采用上滴定法达到Zeposia的维持剂量。
多发性硬化（MS）是一种免疫系统攻击覆盖神经的保护性髓鞘的疾病，造成损害性损伤，使信号更难在每个神经细胞之间传播。这种“信号崩溃”可导致疾病症状和复发。 
批准日期：2020年3月25日 公司：新基制药 
ZEPOSIA（盐酸奥扎莫德 [ozanimod]）胶囊，用于口服
美国初次批准：2020年
作用机理
Ozanimod是一种鞘氨醇1-磷酸（S1P）受体调节剂，可与S1P受体1和5高亲和力结合。Ozanimod阻断淋巴细胞从淋巴结流出的能力，从而减少外周血中的淋巴细胞数量。唑尼莫德在多发性硬化症中发挥治疗作用的机制尚不清楚，但可能涉及减少淋巴细胞向中枢神经系统的迁移。
适应症和用途
ZEPOSIA是一种鞘氨醇1磷酸受体调节剂，可用于治疗复发性多发性硬化症（MS），包括临床成人孤立的综合症，复发型疾病和活动性继发性疾病。
剂量和给药
启动ZEPOSIA之前需要进行评估。
开始治疗需要滴定。
推荐的维持剂量为每天口服0.92mg。
如果在治疗的前两周内未服药，请重新开始滴定方案。
剂量形式和强度
胶囊：0.23mg，0.46mg，0.92mg
禁忌症
在过去的六个月中，经历过心肌梗塞，不稳定型心绞痛，中风，短暂性脑缺血发作，需要住院治疗的失代偿性心力衰竭或III或IV级心力衰竭。
除非患者具有起搏器功能，否则存在Mobitz II型二级或三级房室传导阻滞，病态窦房结综合征或窦房阻塞。
严重的未经治疗的睡眠呼吸暂停。
同时使用单胺氧化酶抑制剂。
警告和注意事项
感染：ZEPOSIA可能会增加感染的风险。开始治疗前，请获取完整的血液计数（CBC）。治疗期间以及停药后3个月监测感染情况。对于活动性感染的患者，请勿开始使用ZEPOSIA。
缓慢性心律失常和房室传导延迟：ZEPOSIA可能导致心率短暂下降；开始治疗需要滴定。在开始ZEPOSIA之前，请检查心电图（ECG）以评估先前是否存在心脏传导异常。考虑进行传导性异常或与其他可降低心率的药物同时使用的心脏病咨询。
肝损伤：如果确认严重肝损伤，则中止治疗。启动ZEPOSIA之前，请先进行功能测试。
胎儿风险：有生育能力的妇女应在治疗期间和停用ZEPOSIA后3个月内使用有效避孕措施。
血压升高（BP）：在治疗期间监测血压。
呼吸作用：可能导致肺功能下降。临床上有评估的肺功能（例如肺量计）。
黄斑水肿：服用ZEPOSIA时，如果视力有任何变化，建议立即进行眼科评估。糖尿病和葡萄膜炎会增加黄斑水肿的风险；有这些病史的患者应在开始治疗前对眼底包括黄斑进行眼科评估。
不良反应
最常见的不良反应（发生率≥4％）：上呼吸道感染，肝转氨酶升高，体位性低血压，尿路感染，背痛和高血压。
要报告可疑的不良反应，请致电1-888-423-5436与CelgeneCorporation或致电1-800-FDA-1088或访问FDA，或访问www.fda.gov/medwatch。
药物相互作用
疫苗：在使用ZEPOSIA治疗期间以及治疗后3个月内，请勿使用减毒活疫苗。
强效CYP2C8抑制剂：不建议同时给药。
BCRP抑制剂：不建议同时使用。
CYP2C8强诱导剂：应避免同时给药。
包装供应/存储和处理方式
供应方式
ZEPOSIA具有以下剂量强度的胶囊剂：
Ozanimod 0.23mg：浅灰色不透明主体/浅灰色不透明帽子，帽子上印有黑色墨水“ OZA”，身体上刻有“ 0.23mg”
Ozanimod 0.46mg：浅灰色不透明主体/橙色不透明帽，帽上印有黑色墨水“ OZA”，主体上刻有“ 0.46mg”
Ozanimod 0.92mg：橙色不透明主体/橙色不透明帽，帽上印有黑色墨水“ OZA”，主体上刻有“ 0.92mg”
提供以下强度和包装配置的胶囊：
套餐配置       压片强度          NDC
瓶：30粒       0.92毫克      59572-820-30
7天入门包   7胶囊入门包装，  59572-810-07
            包含：0.23毫克
            胶囊和0.46毫克
               胶囊

入门套件   37胶囊入门套件    59572-890-91
（7天入门  ，包括：
套件和0.92 7胶囊入门包       59572-890-07
毫克 30计  装，其中包含（4）
数瓶）    0.23毫克胶囊和（3）
           上限0.46毫克
        一瓶含有（30）0.92   59572-890-30
             毫克胶囊
存储
存放在20°C至25°C（68°F至77°F）; 允许在15°C到30°C（59°F到86°F）之间进行偏移[请参阅USP控制室温度]。
完整说明资料附件：
https://packageinserts.bms.com/pi/pi_zeposia.pdf
FDA Approves Zeposia(ozanimod)for Relapsing Forms of Multiple Sclerosis
U.S. Food and Drug Administration(FDA)approved Zeposia(ozanimod)for the treatment of adults with relapsing forms of multiple sclerosis(RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Zeposia, an oral medication taken once daily, is the only approved sphingosine-1-phosphate(S1P)receptor modulator that offers RMS patients an initiation with no genetic test and no label-based first-dose observation required for patients.
An up-titration scheme should be used to reach the maintenance dosage of Zeposia, as a transient decrease in heart rate and atrioventricular conduction delays may occur.
About Multiple Sclerosis
Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves.The myelin damage disrupts communication between the brain and the rest of the body.Ultimately, the nerves themselves may deteriorate—a process that's currently irreversible.
RMS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function.14 These attacks—often called relapses, flare-ups or exacerbations—are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely with no apparent progression of disease.14 RMS is the most common disease course at the time of diagnosis.14 Approximately 85% of patients are initially diagnosed with RMS, compared with 10-15% with progressive forms of the disease.
About Zeposia (ozanimod)
Zeposia® is a sphingosine 1-phosphate(S1P)receptor modulator that binds with high affinity to S1P receptors 1and Zeposia blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood1 The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system.
Zeposia is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn's disease.
Indication
Zeposia is indicated for the treatment of relapsing forms of multiple sclerosis(MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
IMPORTANT SAFETY INFORMATION
Contraindications:
Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker
Patients with severe untreated sleep apnea
Patients taking a monoamine oxidase (MAO) inhibitor
Infections: Zeposia may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving Zeposia. Obtain a recent(i.e.,within 6 months or after discontinuation of prior MS therapy)complete blood count (CBC) including lymphocyte count before initiation of Zeposia. Delay initiation of Zeposia in patients with an active infection until the infection is resolved. Consider interruption of treatment with Zeposia if a patient develops a serious infection.Continue monitoring for infections up to 3 months after discontinuing Zeposia
Herpes zoster was reported as an adverse reaction in Zeposia-treated patients.Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate(S1P)receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus(VZV), should be tested for antibodies to VZV before initiating Zeposia. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with Zeposia
Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator.If CM is suspected, Zeposia should be suspended until cryptococcal infection has been excluded.If CM is diagnosed, appropriate treatment should be initiated.
Progressive Multifocal Leukoencephalopathy(PML)is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. No cases of PML were identified in active-controlled MS clinical trials with Zeposia. PML has been reported in patients treated with S1P receptor modulators and other MS therapies and has been associated with some risk factors.If PML is suspected, withhold Zeposia and perform an appropriate diagnostic eva luation.If confirmed, treatment with Zeposia should be discontinued
In clinical studies, patients who received Zeposia were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS. Concomitant use of Zeposia with any of these therapies would be expected to increase the risk of immunosuppression. When switching to Zeposia from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects
Use of live attenuated vaccines should be avoided during and for 3 months after treatment with Zeposia.If live attenuated vaccine immunizations are required, administer at least 1month prior to initiation of Zeposia
Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of Zeposia may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of Zeposia without dose escalation may result in greater decreases in heart rate. If treatment with Zeposia is considered, advice from a cardiologist should be sought for those individuals:
with significant QT prolongation
with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
with a history of Mobitz type II second-degree or higher AV block, sick-sinus syndrome, or sinoatrial heart block 。