2014年5月—2015年3月美国FDA批准的突破性治疗药物

FDA突破性治疗药物指定评审新政的实施填补了治疗某些疾病药物的空白,并得到制药企业的积极响应.药品评价与研究中心(CDER)截止到2015年3月,生物药品评价与研究中心(CBER)截止到2015年1月,FDA共收到299项突破性治疗药物申请,其中授权87项,拒绝161项,其余51项处在审查中,2014年5月—2015年3月获批了18项突破性治疗药物,从药物治疗类别、作用靶点或机制、获得批准上市情况以及不良反应等方面重点介绍其中的突出品种.     

美国新增加速审批通道——突破性药物认定

突破性药物认定是新增的加速审批程序,其作为《美国食品药品管理局安全和创新法案》（FDASIA）的一部分,于2012年7月签署成为法律。美国在20多年前就设置了加速新药上市的特别审批通道,包括优先审评、加速审批和快速通道。而突破性药物认定与上述审批通道的差异在于,只要早期临床数据能够证明在严重或致死疾病的治疗方面与现有药物相比具有实质性改进,即可获得上市批准。一些药物在研发早期即表现出非常显著的活性,而该程序的目的正是加快这些药物的审批进程。     

罗氏单抗药物 ACTEMRA/RoACTEMRA 获 FDA 授予突破性药物资格

瑞士制药巨头罗氏（Roche）单抗药物 ACTEMRA/ RoACTEMRA（欧洲以外名为 ACTEMRA,通用名：tocilizumab,托珠单抗）在美国监管方面传来喜讯。FDA 已授予 ACTEMRA/ RoACTEMRA 治疗系统性硬化症（SSc）的突破性药物资格（BTD）。BTD 是 FDA 在2012年创建的一个新药评审通道,旨在加快开发及审查治疗严重的或威胁生命的疾病的新药。获得 BTD 认证的新药,在研发时能得到 FDA 高层官员在内的更加密切的指导,保障在最短时间内批准上市,为患者提供新的治疗选择。FDA 授予 ACTEMRA/ Ro-ACTEMRA 治疗系统性硬化症（SSc）的突破性药物资格（BTD）,是基于一项Ⅱ期临床研究 faSScinate 的数据。该研究第一阶段数据显示,尽管在治疗的24周时,未能达到改善皮肤增厚的主要终点,但观察到了一个有意义的改善趋势。     

美国FDA批准诺华公司抗疟复方产品Coartem并授予其优先审批证件

美国FDA近期批准了诺华公司的抗疟复方片剂产品Coartem(蒿甲醚+苯芴醇)用于治疗成人和体重5 kg以上儿童由恶性疟原虫引起的急性轻症疟疾感染,但未批准其用于治疗重症疟疾和预防疟疾,同时依据一项鼓励开发热带疾病治疗药物的新政策,授予这家瑞士公司首个优先审批证件.FDA的这项新政策规定,若某药品是被开发用于治疗或预防美国FDA修正法案(FDAAA)中所列16种疾病以及含有先前在美国尚未获准的活性成分,那么该药品则有资格获得一份优先审批证件,即使像Coartem已在全球广泛上市的药品也可获得.诺华公司可利用此证件,获得未来某个新药的6个月优先审批权,也可出售此证件而获取收益,购得此证件的企业又可以此将新产品更快地投放市场.某些专家预测,该证件售价可达亿万美元.     

他司美琼-Ⅱ

<正>他司美琼(tasimelteon)是Vanda制药公司开发的用于治疗盲人非24 h睡眠觉醒障碍的药物,以更新公告完善适应症信息的方式于2014年10月2日再次获得FDA批准[1],它是FDA批准的首个用于治疗该适应症的新药,经过快速优先审批程序并被授予孤儿药资格。商品名为Hetlioz,该药为硬胶囊剂,曾经于2014年1月31日首次获得美国FDA批准上市[2]。     

美国孤儿药资格认定及批准上市情况分析

目的： 系统了解美国孤儿药批准情况,分析资格认定和审批趋势。方法：以美国食品药品监督管理局(FDA)数据库Drugs@ FDA和孤儿药资格认定和批准在线数据库为主要数据来源,系统收集美国FDA自1983至2020年认定和批准的孤儿药信息,从审批数量、审批时间、治疗领域等方面进行统计分析。结果：1983-2020年FDA共认定孤儿药资格5757个,批准孤儿药适应症943个。从孤儿药认定身份到获批上市平均所需的时间为5.14年。批准的孤儿药适应症中抗肿瘤和免疫机能调节相关适应症最多,为 408个,占比为43.27%。结论：自1983年《孤儿药法案》实施以来,FDA授予的孤儿药资格数量和批准的孤儿药适应症数量呈现明显的增长趋势。     

04075 FDA授予XP12B快速审批地位

美国FDA已授予Xanodyne制药公司的XP12B快速通道审批地位，该药是一种用于治疗大量月经出血的药物，正在进行Ⅲ期临床试验以评价其疗效。目前美国FDA尚未批准任何药物用于这一适应症。     

2017年10月FDA批准新药概况

2017年10月,FDA批出 1 个新分子实体药品(表 1),为治疗淋巴瘤药品 Calquence(acalabrutinib). Calquence 获"突破性治疗药物"和"孤儿药"指定以及"优先审评"地位,通过加速审批程序被批准用于既往接受过至少一次治疗的的套细胞淋巴瘤(mantle cell lymphoma, MCL)成年患者的治疗.     

FDA批准预后不良的急性髓性白血病治疗药物Vyxeos

<正>2017年8月3日,美国食品和药物管理局(FDA)批准Vyxeos治疗两类成人急性髓性白血病(AML),主要针对"与化疗或放疗有关的AML"(TAML)和由于血液疾病或其他癌细胞突变导致的"骨髓增生异常相关变化的AML"(AML-MRC)。Vyxeos是一款包含化疗药物柔红霉素和阿糖胞苷的复方脂质体注射剂,由Jazz Pharmaceuticals公司生产。Vyxeos获得了FDA优先审评、突破性治疗和孤儿药资质。FDA肿瘤学卓越中心主任、FDA药品审评     

FDA批准Alimta（pemetrexed disodium）与顺铂联用治疗恶性胸膜间皮瘤（一种罕见的癌症）

FDA批准Alimta(pemetrexed disodium)与顺铂联用治疗恶性胸膜间皮瘤(一种罕见的癌症)Alimta早先已被FDA指定为治疗此罕见病用药,它也是得到FDA批准的第一种治疗此症的药物。一项随机临床试验比较Alimta与顺铂联用及单独应     

2016年美国FDA批准的新药分析

目的：对2016年美国FDA批准的新药进行分析,供医药界和相关管理部门参考。方法：通过FDA官网的药物创新专栏与Drugs@FDA数据库查阅、收集FDA批准新药的信息,进行统计分析。结果与结论：2016年,FDA共批准22个新药,比2015年大幅减少,也低于1997-2016年的年均新药数量（28个/年）,其中新药申请15个,生物制品许可申请7个。批准新药中获得优先审查、快速通道、突破性治疗和加速审批资格的分别为15个、8个、7个和6个,批准孤儿药9个。批准新药的治疗领域以抗感染药、抗肿瘤药和神经系统用药为主,剂型以注射剂、片剂为主。     

罕见病药品贝林妥欧单抗临床研发和风险获益评估及启示

贝林妥欧单抗（通用名blinatumomab、中文商品名贝利妥、英文商品名Blincyto）于2014年获美国食品药品管理局（FDA）批准上市，是全球首个治疗急性淋巴细胞白血病（ALL）的双靶点抗体药物，持证商为美国安进公司（Amgen）。作为创新生物制品，其上市申请、审评和批准过程分别经历了FDA孤儿药（orphan drug）资格认定、突破性治疗药品（breakthrough therapy）资格认定、优先审评（priority review）资格认定、附条件批准（accelerated approval）等创新药的优先和特殊政策。通过文献研究法，收集、整理、分析了FDA首次批准贝林妥欧单抗的审评报告及相关文献，在全面了解该品种特点及审评审批过程的基础上，以有效性研究评价模式为切入点，尝试总结“以患者需求为核心，以临床价值为导向”的创新药物审评审批理念的具体实践经验，以期为我国新药研发和审评提供借鉴。     

Examination of risk evaluation and mitigation strategies and drug safety in the US

BackgroundThe Food and Drug Administration Amendment Act of 2007 (FDAAA 2007) enabled the US Food and Drug Administration (FDA) to require risk evaluation and mitigation strategies (REMS) for a drug or biologic to ensure that its benefits outweigh the risks.ObjectiveThis study sought to evaluate REMS approved and released by the FDA since the program inception in 2008, to assess the characteristics of REMS approved and to calculate the time lag between FDA drug application approval and REMS approval.MethodsData were derived from Approved Drug Products with Therapeutic Equivalence Evaluations, Approved REMS and Drugs@FDA. Data included generic availability, application type and approval date, therapeutic class and FDA review class, orphan designation, priority review and market status.ResultsThe FDA approved REMS for 259 marketing applications (217 new drug applications -NDAs, 10 abbreviated NDAs, and 32 biologic license applications) in the study period. The FDA granted orphan designation to 11.4% of active ingredients with REMS and priority review to 38.4% of the NDAs with REMS. The largest number of REMS approvals was for nervous system products (31.8% of total approved REMS) and antineoplastic and immunomodulating agents (15.3%).ConclusionsThe FDA approved REMS for one in three biologics and one in thirteen chemical entities available in the market. A pharmaceutical product can be in the market for an average of 14 years before the FDA identifies and evaluates the risk problems that warrant the approval of a REMS.     

A Note on Breast Cancer Trials With pCR-Based Accelerated Approval

Accelerated approval by the Food and Drug Administration (FDA), under the agency’s Fast Track review designation, allows early approval of drugs to treat serious diseases and fill an unmet medical need based on a surrogate endpoint. In May 2012, FDA issued a draft Guidance for Industry on the accelerated approval of breast cancer drugs based on the surrogate endpoint “pathologic complete response” (pCR). The research reported in this article investigates potential issues in designing clinical studies for pCR-based accelerated approval. The correlation between pCR and long-term survival was investigated. Two sample comparisons based on a conditional survival model under different assumptions were performed and are discussed along with simulation results. The findings from this research may shed some light on the implementation of the FDA draft guidance.     

Cross-national comparative study of orphan drug policies in Saudi Arabia,the United States,and the European Union

BackgroundRare diseases are chronic, serious, and life-threatening conditions that have not received sufficient attention from drug developers due to their rarity. Policies have been implemented to encourage research and incentivize the development of orphan drugs. However, the implementation of these policies has been inconsistent worldwide.ObjectiveThe primary aim of this study was to compare orphan drug policies in the United States, Europe, and Saudi Arabia (SA) and assess their impact on the number of approved indications.MethodLists of all drugs granted orphan designations and authorized for marketing in the United States, European Union, and SA were extracted using orphan drug lists available in regulatory body databases. The availability of these drugs, regarding their approval for orphan indication and designation, was assessed and classified using Anatomical Therapeutic Chemical codes.ResultA total of 792 orphan drug designations with at least one authorized indication were identified in this study. Of these, 92% were designated by the Food and Drug Administration (FDA), and 27% were designated by the European Medicine Agency (EMA). The FDA, EMA, and Saudi Food and Drug Authority approved 753, 435, and 253 orphan drugs, respectively.ConclusionFewer orphan drug approvals were found in SA than in the United States and Europe. This highlights the need to focus on rare diseases and orphan drugs and for policies to be created in SA to attract pharmaceutical markets and fulfill unmet orphan drug approval needs.     

美国与欧盟孤儿药研发上市管理制度及对我国的启示

目的通过对美国与欧盟对孤儿药研发上市相关管理政策的分析,为我国孤儿药研发上市管理提供借鉴。方法分析美国和欧盟药政管理部门公开的法规文献和数据库检索数据,总结其对孤儿药的激励政策,分析获得孤儿药资格认定和批准上市的药物特点。结果美国和欧盟对孤儿药研发均颁布实施了诸如市场独占期、政府资助、审评专家对研究方案的指导等相应的激励政策。研发机构应采取及早申请孤儿药认定、多途径发现孤儿药及孤儿药的再开发等研发策略。结论美国和欧盟对孤儿药的研发与上市激励政策,刺激了制药企业对罕见病治疗药物的研发热情,有效缓解了罕见病无药可治的现状,对我国制定相关孤儿药政策提供了有益的借鉴。国内创新型制药企业应尽早布局孤儿药的研发,应重点关注国内已经被大众接受的罕见病和治疗,以及超说明书使用的问题;重点关注生物仿制药如单克隆抗体的研发动态;重点关注国际孤儿药专业公司的研发动态,使孤儿药在国内相关法律法规建立健全后,立即有所响应,尽早抢占孤儿药研发的领先地位和市场地位。     

突破性治疗药物程序在药品注册体系中的作用及展望

目的：进一步完善我国突破性治疗药物程序并发挥其在药品注册体系中的作用。方法：通过梳理美国食品药品管理局(FDA)突破性治疗认定(BTD)、欧洲药品管理局(EMA)优先药物计划 (PRIME)和我国国家药品监督管理局(NMPA)突破性治疗药物程序和案例,进一步探索优化我国突破性治疗药物程序在药品注册体系中的发展方向。结果与结论：FDA、EMA和NMPA的药品注册体系中均具有突破性药物治疗程序。FDA自2012年7月实行加快程序中的突破性治疗认定,通过大量案例积累了相对完善的管理经验,EMA的PRIME专人专管的政策支持以及明确的资格申请数据要求,均具有借鉴意义。我国突破性治疗药物法规于2020年落地实施后,至今也积累了一定案例。通过对FDA、EMA和 NMPA关于BTD的法规对比,为我国突破性治疗药物程序实施提供建议。     

FDA Breakthrough Therapy Designation: Evaluating the Quality of the Evidence behind the Drug Approvals

The United States Food and Drug Administration (FDA) has created approval pathways and designations to accelerate access to medications indicated for serious or life‐threatening conditions with limited treatment options. Implemented in 2012, the most recent of these is the breakthrough therapy designation (BTD). The purpose of this article was to review the evidence surrounding approval of medications with nononcology indications approved with the BTD designation from 2012 to 2016. Fifteen medications were identified for eight conditions, ranging from conditions that are relatively common, such as chronic hepatitis C infection, to those that are extremely rare, such as lysosomal acid lipase deficiency. The quality of evidence behind these approvals was highly heterogeneous. Much remains unknown about the safety and efficacy of many agents approved through the BTD. Health care professionals should be aware of these limitations to better educate patients and other providers appropriately.     

New drugs and FDA publicity

The Food and Drug Administration (FDA) has been criticized for publicly announcing the approval of significant new drugs. This policy was formulated for two reasons: to encourage better public understanding of the benefits and limitations of new drugs and to account to the public for new drug approvals. The FDA makes such announcements only for major new drugs. This policy, which started in 1978, seems to have worked well in accomplishing the FDA's objectives.