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创新药的春天!2019国家医保目录调整品种分析

孔雀 孔雀 来源:医药魔方
2019-03-13
创新药 医保
原文

按照国家医保局的2019年重点工作任务安排,预计近日就会启动新一轮国家医保目录调整工作。参考2017版目录的工作进度,预计方案和基础数据库会在3-4月份先后确定,然后在5-6月份完成专家咨询与遴选,7-9月份进行医保准入产品谈判。如一切进展顺利的话,那么新医保目录有望在国庆节之前出台,在年内执行。

 

由于本次目录调整工作时间紧,任务重,而且距离2017版目录时间又不算太长,所以可以大胆猜测一下:1)基础数据库可能会采用2017版目录调整时的数据库,然后再加入2017版目录数据库截止日之后上市的新药数据,这其中应该会重点考虑创新药部分。2)应该会对各省增补和谈判的数据做一个梳理作为参考。3)专家库方面,由于在2017版国家目录及省级评审时,各省都建立好了各自的专家库,所以,也仅需要在之前的基础上再做小幅的更新即可直接使用。

 

至于具体评审方案,具体品种能否进入目录,大致原则应该还是笔者在2017年文章《终极猜想 · 最有可能入围新版医保目录的品种分析》中提到的临床需求、经济因素和市场因素,在此不再赘述。前文中提及的没有明确的目录与谈判的边界,随着两轮医保谈判的开展,现在也可以推断出个大概的原则:一方面应该是独家品种,且绝大多数还在专利期内,另一方面应该是与目录内同类或同治疗领域产品相比,价格较为昂贵,需要进一步通过谈判来降低价格。另外,这次目录评审会涉及11个非医保的国家基药产品,虽然基本药物和医保目录出自于2个部委,也不是说基本药物都100%要进入医保目录,但在评审时应该还是会有一定的加成的。


根据从医药魔方PharmaGo查询到的2016年至今在国内批准上市的新药来看,虽然整体数量上仍是跨国公司的创新药产品占大多数,但国内企业也开始有了很多创新产品上市,数量上远远超过了2017版目录评审之时,这是非常让人欣喜的进步。虽然理论上医保没有鼓励国产创新的义务,但从实际的既往经验来看,多少还是会有一定的额外加成。


本文主要是对2019国家医保目录调整中的一些热门品种做出一些分析预测,行文时依据国家医保局重点工作任务中着重提及的“癌症等重大疾病、慢性病、罕见病及儿童用药等”做了简单分类。抛砖引玉,还请大家多提宝贵意见。


◆  ◆  ◆糖尿病药物


1. 胰岛素


当前仍没有纳入目录的重磅产品只有德谷胰岛素了,从德谷胰岛素当前的定价策略来看,似乎是对于直接进入目录志在必得,所以大概率会不经过谈判,直接进入目录(凡例)。

 

2. GLP-1类


考虑到利拉鲁肽已经在2017年谈判进入医保,在本次调整中,艾塞那肽、艾塞那肽缓释微球、利司那肽、度拉糖肽及国内的贝那鲁肽均有望进入目录。其中艾塞那肽其实是在国内上市最早的GLP-1,但在2017年调整目录时并没有通过专家遴选,这里面可能有当时国内销售权益转移的问题,也可能是由于从产品自身角度来看,一天2次给药及相对较高的价格形成了一定的阻碍。当前艾塞那肽从全国中标价来看仍然会比利拉鲁肽的谈判价格高一些,而缓释微球剂型还要更贵一些,但胜在一周一次的依从性。国内的贝那鲁肽一天3次且当前价格最贵,想进医保估计要大幅降价了。而利司那肽和度拉糖肽当前尚不能查到中标数据。


Anyway,无论是哪家的GLP-1,至少当前有利拉鲁肽作为支付标准的参考,预计谈判后的价格都不会超过40元/日,其中艾塞那肽缓释微球和度拉糖肽作为一周一次的长效制剂,如果能谈成,可能会稍高一些。我个人最期待的索马鲁肽及其口服制剂,从审评进度来看,肯定是赶不上这次目录了。同样赶不上的可能还有重大专项支持的聚乙二醇洛塞那肽。


本类别药物的适应症限制应该会参考利拉鲁肽,越贵的产品限制可能会更严格。

 

3. SGLT-2抑制剂


跟进入2017版目录有5个DPP-4药物一样,本次达格列净、恩格列净、卡格列净3个SGLT-2抑制剂很有希望进入目录,唯一问题在于价格。DPP-4的日费用在10元以内,相比之下SGLT-2抑制剂的价格还是略高一些,或许有些产品会启动谈判。达格列净实际日费用最低,又有国家基药加成,直接进入目录的可能性是最大的。本类别适应症限制应该会参考DPP-4,即限二线用药。

 

4. 复方产品


进入2017版目录的5个DPP-4抑制剂当中,有4个上市了二甲双胍复方产品,SGLT-2中的恩格列净也上市了二甲双胍复方产品,这无疑是因为二甲双胍是糖尿病治疗的绝对一线药物。国际上,无论是DPP4还是SGLT2,二甲双胍复方产品的销量都还不错,对于高血压或糖尿病等需要联合用药的慢病来说,复方产品可以提高患者的依从性。但对于国内的医保目录评审来说,如何为复方产品中的二甲双胍买单才是关键。


当前,即使是原研的二甲双胍价格也并不太贵,日费用也仅在3元左右,更何况二甲双胍肯定是第二批国家带量采购的品种,届时日费用肯定会低于1元甚至0.5元。所以,对于这些复方产品来说,如果采取类似于国外的买主药送辅药的定价策略(注:比如恩格列净二甲双胍只卖恩格列净的价格),尽可能早一些将产品进入医保才是正确的选择。特别是几个专利即将到期的产品,或许还可以通过独家的复方产品来尽可能拖延一下国家带量采购带来的专利悬崖。从当前的中标数据来看,西格列汀复方中的二甲双胍是最便宜的,相对其他产品来说可能更主动一些,而恩格列净复方由于上市时间过短,可能难度上会大一些。复合药一般来说适应症限制会等同主药。

 

5. 其他


当前国内GLP-1、DPP-4、SGLT-2均有不少在研产品,从当前的审评进度来看,估计都赶不上此次医保目录评审了,其中值得一提的是前些日子炒的比较热的海外代购产品长效DPP-4抑制剂曲格列汀。这个产品由于国内专利方面的一些问题,这两年也是国内仿制申报的大热门。但冷静的分析一下,长效DPP4包括曲格列汀和奥格列汀,全球范围仅有日本上市,其中奥格列汀在欧美投入了9个III期临床入组7000多病人,最终还是放弃了上市,一方面是产品自身安全性、依从性等原因,另一方面重要原因还是价格与医保支付。


未来国内医保的终极目标是实施价值导向的战略性购买,按照这个既定目标,不论未来医保药品目录采取什么形式管理,所注重的都应该是真实临床价值和价格的综合考量。据此,国内企业无论是创新也好,仿制也好,都应该审慎考虑自身的产品管线和利润预期。曲格列汀未来国内的上市、医保支付和市场前景将会是一个很好的例子,但在此篇幅有限,就不做过多展开了,有机会或许可以单开一篇来聊聊。


◆  ◆  ◆心血管药物


1. LCZ696


沙库巴曲缬沙坦是此次医保目录调整的大热门之一,唯一的问题还是在价格方面。此产品国内的定价相对于美国来说略微低廉一些,但比起其他心衰药物还是贵出太多了。按最新中标价格来核算的话,日费用高达56元。可供参考的是,2017版新进目录的心衰新药伊伐布雷定的日费用仅为17.3元。所以,本品虽然进入目录的概率很大,但同时谈判降价的概率也是蛮大的。视谈判结果,本产品有可能会加适应症限制,如果限成二线用药还好,但如果限成其他心衰药品不耐受则会比较伤。

 

2. PCSK9


本类产品当前国内上市的仅有依洛尤单抗,但阿利珠单抗两周前获得了CDE的优先审评资格,或许还能在截止日前赶上末班车。从疗效和实际的临床意义来说,PCSK9是个不错的品类,毕竟临床他汀不耐受的概率约有15%,但同上述的沙库巴曲缬沙坦一样,即使在国外医保支付相对国内宽松的条件下,相对高昂的定价也对支付方造成了不小的支付压力。这其实很好理解,虽然创新靶点相对于传统比较成熟的治疗方案稍有改善,但价格高达10余倍,任何一个支付方都会仔细验证其药物经济学方面的证据是否充分。鉴于此,本品类本次能否进入目录还存在较大疑问,即使进入,也会是在谈判大幅降价,外加适应症限制为他汀不耐受的前提之下。

 

3. 复方产品


替米沙坦氨氯地平、奥美沙坦酯氨氯地平、培哚普利氨氯地平、氨氯地平叶酸……不要惊讶,这两年国内就是上市了这么多的氨氯地平复方制剂。一方面是因为氨氯地平自身良好的疗效、安全性以及半衰期,国际上联用氨氯地平的复方产品也比较多,另一方面其实也应该有一些中国特色。不同于国际上使用的降压药以ACEI和ARB居多,中国市场份额最大的品类要属CCB,其中最大的产品就是氨氯地平。


这几个产品里比较有特色的是培哚普利氨氯地平,毕竟ASCOT研究作为近二十年来最经典的心血管临床研究之一,所采用的主药就是培哚普利和氨氯地平,从循证证据角度来看这个产品无疑是最充分的。而奥美沙坦酯氨氯地平可能会仿照奥美沙坦酯单方和奥美沙坦酯氢氯噻嗪一样加适应症限制,比起其他ARB来说会比较伤。氨氯地平叶酸的价格现在还查不到,但是因为和依那普利叶酸是同一个厂家,估计定价也不会太低。依那普利叶酸作为国产创新,价格比原研还贵,但也很早就进了医保目录,所以氨氯地平叶酸就算贵点儿,从日治疗费用来说只要定价别太离谱,应该还是能进入目录的。


说起心血管复方产品,还有两个上市较早的经典产品这次有望进入目录,一个是培哚普利吲达帕胺,另一个是辛伐他汀依折麦布,这两个产品在全国多数地方也都增补进了省级目录。

 

行文至此,恰逢国务院2019政府工作任务出台,文中提及“做好常见慢性病防治,把高血压、糖尿病等门诊用药纳入医保报销。”,故可以理解为前文中高血压及糖尿病产品有望在此次目录获得额外加成,相对名额限制有望宽松一些,会进入更多产品。


◆  ◆  ◆中枢神经系统疾病药物

 

1. 精神科用药


布南色林和鲁拉西酮,同一家公司一口气上市了2个新的抗精神分裂症新药,都还是有一定特色的。布南色林的定价也不算太贵,鲁拉西酮现在还查不到价格,但应该也不会太贵,这两个产品都有挺大希望进入目录。精神科产品虽然看似比较小众,但从医保目录方面来看一直是有额外加成,非医保的产品比较少,而且限制相对也比较少。

 

2. 神经内科用药


帕金森病领域这两年上市了不少新药,首先是第二代MAO-B抑制剂雷沙吉兰,这个产品最大的问题是比较贵,比在目录内的第一代司来吉兰贵10多倍。当然雷沙吉兰的疗效也好不少,国内很多病人在上市前都在吃印度版,如果这次能降价进目录无疑对患者来说是个福音。


另一个是刚刚上市的罗替高汀贴片,帕金森病人往往依从性较差,把药物做成外用的透皮贴剂毫无疑问可以提高患者的依从性,应该说也是很有特色的。进目录的问题同雷沙吉兰,想用足剂量的话,就和雷沙吉兰的日费用差不多了,也属于比较贵的,看看能不能有谈判的机会吧。


恩他卡朋双多巴是一个三方复合药,单方都已在目录之内,复方能提升依从性,价格方面也还可以,理论上进目录没问题,但帕金森这方面有点儿小众,能不能进入专家视野是个问题。


抗痴呆领域也新上市了一个利斯的明透皮贴,这个产品的口服剂型叫做卡巴拉汀,是已经在目录里的,估计未来药监机构会把通用名统一的。抗痴呆4个一线药物其实全在目录内的,2017目录还增补了多奈哌齐口崩片,所以感觉利斯的明透皮贴进目录机会也挺大的,特别是现在看来定价并不太贵,而且仿制产品也快上市了。


癫痫领域新上了拉考沙胺(拉科酰胺),由于刚上市,定价还不清楚,如果定价比较合理的话,进入目录的概率挺大的,特别是仿制品也快上市了。在这里感慨一下,字母司的癫痫药物可真多,未来还会有布瓦西坦上市,有儿童适应症应该比较容易进目录,但这次是赶不及了。


◆  ◆  ◆呼吸科药物


奥马珠单抗是全球首个批准治疗中至重度哮喘的靶向治疗药物,产品是很好,奈何实在太太太贵了,10万+的疗程费用,并不低的发病率,就算可以谈判降低一部分价格,也不是很看好医保基金能够负担的起这个产品。

 

茚达特罗格隆溴铵、乌美溴铵维兰特罗、噻托溴铵奥达特罗、糠酸氟替卡松维兰特罗、奥达特罗,当前价格数据多数还查不到,本类一般来说价格不太贵就能进目录,价格维度可以参考2017新进目录的茚达特罗。


贝达喹啉、德拉马尼是2个抗结核耐药的新药。这2个产品联用可以说是目前耐多药结核的最后防线,但医保是否会覆盖这2个产品还不好说。


◆  ◆  ◆肿瘤及重大疾病药物


1. PD-1


经过了2018年的17个抗癌药谈判,还没进目录的最热门的产品毫无疑问是PD-1了,当前上市的有纳武利尤单抗(O药)、帕博利珠单抗(K药)、特瑞普利单抗、信迪利单抗,而卡瑞利珠单抗和替雷利珠单抗或许也能赶上末班车。


从谈判进目录的角度来看,应该说每家都有成功的可能,也都有失败的可能。首先基本上可以明确的是,谈判会按照适应症来谈,如果某产品谈判时已经有多个适应症获批,谈出来的结果很可能也会仅基于1个适应症,而医保支付限制会严格遵照谈出来的这1个适应症,后批的适应症等同于非医保,也就是说,虽然PD-1的整体市场潜力极大,但本次医保谈判支付仅仅会涉及其中的一小部分。


参考的价格维度方面,国际价格其实意义不大,O药K药国内定价都比国外低一些,而其他产品国外没上市也没价格;慈善价格会被参考;最主要还是要对疗效和价格做综合考量,这其中既有相对于传统疗法,包括一线化疗和现已在目录的靶向药的比较,也会做不同PD-1产品间的横向比较。所以,最终价格虽然不至于低到几百元一支那么惨烈,但要做好相对于现有价格大幅降价的心理预期。这对于外企的O药K药来说,得能接受中国价格是全球最低,而对于国内企业来说,也要做好现有“低价”再打个几折的准备。


谈判结果上,相比起来我个人更看好外企一些,毕竟无论从临床证据的充分性,还是从谈判准备和人员专业程度方面来看,外企都明显要更胜一筹。而从历史上的两轮谈判来看,基本上谈判失败的产品就两种情况,一种是外企谈判的价格远远低于国际价格,特别是对于专利期还较长的产品,降幅是不可接受的;另一种就是少数外企和国内企业,由于缺乏明确的定价策略和专业人才,在谈判时处于完全的被动局面。


特别是医保谈判发展至今,医保方的专业程度和经验都在不断增长,也就是“我们在医保谈判中有更强话语权”(注:此话出自胡静林局长),这时国内企业再派一些业余选手出场,虽然或许这些业余选手在其他如商务或者销售领域也是佼佼者,但假设谈判桌是个足球场,这么玩基本上等同于派中国国乒去和法国国足踢比赛。


另据医药魔方全球新药库NextPharma收录的信息,PD-1/PD-L1可以说是全球最热的靶点,相关项目达到173个。即使大部分产品最终夭折,明后年上市的产品也会超过10个,医保方完全可以采取今年试水的策略,然后再在明后年更新一轮谈判里扩大适应症范围和大幅压低价格,届时,盛况或许会堪比去年的4+7带量采购。虽然结局对于企业来说可能比较残酷,但对于医保方来说,可以实现真正的价值导向的战略性购买,而且对于每一个参保人或者说老百姓来说,我们都是受益者。


2. Her2、CDK4/6


Her2靶点当前有临床意义的适应症主要是乳腺癌。帕妥珠单抗可以认为是曲妥珠单抗的升级产品,吡咯替尼主要优势在于是口服小分子药物,并且可以减轻腹泻的不良反应,这两个产品都可以和曲妥珠单抗联用,来进一步提高Her2阳性患者的生存期。哌柏西利通过抑制CDK4/6应用于HR+/Her2-的乳腺癌患者,是在传统芳香酶抑制剂基础上的突破性改进。从临床需求的角度来看,这3个产品都有充足的理由,只要价格谈判环节能够过关,进入目录问题不大。

 

3. PARP


奥拉帕利是当前国内唯一上市的PARP抑制剂,其他同类产品从进度来看是赶不上了。卵巢癌的靶向药目前就这么一个,进入谈判环节问题不大,价格可能会在现有慈善的基础上再降一些。

 

3. ALK


阿来替尼已经获批,同为二代ALK的恩莎替尼获得了CDE的优先审评资格,或许也能赶上末班车。考虑到一代ALK克唑替尼,二代ALK赛瑞替尼都已经在17种抗癌药时谈判进入目录,所以这2个产品的价格也有了参考区间,进入谈判环节问题不大。

 

4. VEGFR


呋喹替尼是上市有些晚了的国产靶向药,适应症是结直肠癌,同适应症的竞品主要是贝伐珠单抗,价格也有参照,估计谈判准入的概率很大。阿柏西普眼内注射参照产品为雷珠单抗和康柏西普,当前定价也仅比参照产品贵一点点,谈判准入的概率很大。仑伐替尼目前适应症仅有肝癌,参照产品大概是瑞戈非尼,当前定价略贵,不过有慈善,估计谈判到慈善价格左右就可以准入目录。与仑伐替尼最近似的其实是近期“假药”事件的主角卡博替尼,但原研似乎没有中国上市的计划,国内仿制肯定也肯定赶不上本次目录评审了。

 

5. Gnrh受体拮抗剂


地加瑞克这个产品类似于已在目录内的戈舍瑞林植入剂或者亮丙瑞林微球,都是长效的治疗激素依赖型前列腺癌的药物,但略有改进,所以进入目录问题不大,价格可能也会比戈舍瑞林植入剂略贵一些。

 

6. 烷化剂类


美法仑注射剂型属于氮芥类药物,口服剂型已经在目录内了,注射剂从安全性来说是有改善的。苯达莫司汀注射剂属于双功能基烷化剂,结合了氮芥类和亚硝基脲类的特点,而这两类产品大都在目录内。这两个产品只要价格不太贵,进目录问题不大,但这两家公司比较小,产品知晓率是个问题。


7. 紫杉烷类


紫杉醇脂质体的剂型优势还是有的。国内只有两性霉素B、紫杉醇和多柔比星有脂质体的剂型,其中两性霉素B脂质体进了2017的医保目录。应该说脂质体技术可以做到减毒增效,是未来对于传统化疗药物的一个改良方向。同类还有紫杉醇白蛋白,之前没通过专家遴选,八成还是因为太贵又是独家,但现在国内有2家仿制产品上市,进入目录的可能性就大增了。从疗效安全性方面来看,这2个产品对比普通紫杉醇无疑都有明显的改善,但在能否进入目录的问题上,价格还是会起决定性作用。


8. 其他


普乐沙福用于干细胞移植,在国外是孤儿药,但国外的孤儿药概念和国内的罕见病概念不太一样,所以估计不会作为罕见病类参加评审。国内定价未知,但正因为国外是孤儿药所以比较贵,所以能否大幅降价进入目录有些疑问。


芦可替尼用于治疗骨髓纤维化,是17个抗癌药谈判时唯一失败的产品。失败原因八成是因为谈判价格低于国外价格太多,本次不知能否会再给一次机会。即使能给机会,谈判也会比较艰难。好的一点是这个适应症也没有别的药物,而且毕竟有过西妥昔单抗第一次谈判失败但第二次成功的例子,所以还是会有小概率可以谈成功。


◆  ◆  ◆丙肝药物


按我国的丙肝防治指南2015版的流行病学数据,HCV1b和2a基因型在我国较为常见,其中以1b型为主(56.8%),其次为2型(24.1%)和3型(9.1%),未发现基因4型和5型,6型相对较少(6.3%)。混合基因型少见(约2.1%),多为基因1型混合2型。


所以,根据按公司产品来区分方案的话,达拉他韦阿舒瑞韦(1型),奥比帕利达塞布韦(1型),艾尔巴韦格拉瑞韦(1、4型),国产的达诺瑞韦(1型)其实可以划到同一档,而索磷布韦及其复方制剂可以单划一档,索磷布韦维帕他韦(全基因型)又是其中最能打的,更何况还有基药加成,进入目录的概率很大。


本大类竞争激烈,第一档其实也能够覆盖一半以上的患者,所以能谈进的是应该是采用低价策略的产品,而全部谈进的概率不大,索磷布韦维帕他韦谈进的价格也是关键,因为肯定会高于第一档,所以无形中也压低了第一档的价格。


本大类的竞争激烈还源于这次谈判关联到国内第一波医保病人,由于疾病可以治愈,国外的经验表明,谁能以合适的价格取得医保支付,抢到前几波病人就可以赢得大部分市场,而最终市场几乎接近于消失。所以,如果不能赶上此次谈判,如拉维达韦等产品,未来能收获的市场就会很小了。另外,西美瑞韦虽然国内获批,但又基本等于退市了,其实也不失为一种选择,毕竟对于跨国公司来说,国内市场虽大,但如果产出小于投入那就不如放弃,而对于国内大量在研产品来说,未来能否收回成本真的是未知数了。


◆  ◆  ◆艾滋病药物


1. 整合酶抑制剂


多替拉韦及复方制剂多替阿巴拉米(多替拉韦&阿巴卡韦&拉米夫定),拉替拉韦,艾维雷韦的复方制剂艾考恩丙替(艾维雷韦&考比司他&恩曲他滨&丙酚替诺福韦),不知道其中有没有产品可以实现整合酶抑制剂在医保目录零的突破,国际上多数一线治疗方案中含整合酶抑制剂,但国内受限于价格短期内基本无望进入免费用药目录。从治疗费用来看,拉替拉韦已经和目录内的恩曲他滨替诺福韦比较接近,但艾滋病治疗经常联用几类药物,目录进入相对昂贵的药物会对基金造成额外负担,所以或许依旧比较艰难。


2. 长效融合抑制剂


艾博卫泰是国内首个原研抗艾滋病新药,也是全球首个长效的融合抑制剂,比起口服制剂多数一天一次,一天多次的给药方式,这个产品可以做到一周一次给药,是有些特色的,预计会进行谈判。同类品种里短效的恩夫韦肽在目录,但似乎全国断货,中标价格能查询到的也是贵出天际,没有什么参考意义。


3. 蛋白酶抑制剂


达芦那韦考比司他,新上市的增强型,价格也贵,考虑到达芦那韦也没在目录,感觉够呛。同类品种中沙奎那韦在目录,但原研停止进口,国内已经没有有效批文了。


4. 核苷及核苷酸逆转录酶抑制剂


恩曲他滨丙酚替诺福韦这个复方产品可以顺带着和丙酚替诺福韦单药一起介绍。丙酚替诺福韦就是大名鼎鼎的TAF,即替诺福韦二吡呋酯(TDF)的前体药物,理论适应症可以是乙肝和艾滋病,但国内单方目前只批了乙肝,与恩曲他滨的复方以及和整合酶抑制剂组成的复方则是用于艾滋病。价格现在未知,国外是不便宜的,而国内替诺福韦二吡呋酯在4+7时候已经是几毛钱的地板价,丙酚替诺福韦系列产品这次进目录存在一定难度,除非厂家能给出一个很优惠的价格。


◆  ◆  ◆血液科药物


艾多沙班大致可参照利伐沙班或达比加群酯,价格不太贵的话应该能直接进目录,适应症也会限制成房颤。依达赛珠单抗是达比加群酯的逆转剂,价格未知,但猜测会比较贵,而且略小众,进目录希望不大。


比伐芦定适应症是PCI抗凝,同类产品应该是依诺肝素或磺达肝癸钠,但比起前两个的价格,实在是贵出太多了,又不是独家产品,谈判也有难度。瑞替普酶用于急性心梗溶栓,作为急抢救用药,又是新进基药的品种,同类阿替普酶已经在目录了,进入目录希望挺大的。  


艾曲泊帕适应症是原发免疫性血小板减少症(ITP),参照药物TPO是2017新进目录乙类的产品,医保限制中也有ITP,所以只要是定价和TPO接近,进入目录应该问题不大。罗沙司他参照药物EPO,估计也会限肾性贫血,同上只要价格和EPO接近,进入目录应该问题不大。


◆  ◆  ◆罕见病&儿童用药


1. 肺动脉高压


波生坦在2017年谈判失败,但去年进了基药,仿制药也快上市了,只要不再在谈判上失误,这次目录希望就很大。安立生坦借着波生坦谈判失败的机会进了不少省目录,效果和价格都和波生坦差不多,希望也很大。马昔腾坦是波生坦的升级版,但价格要贵出太多了,想谈判进入有点儿难度。


利奥西呱与前述3个内皮素受体的药物不同类,还可以联用,日价格现在大概和波生坦差不多,也比较贵,但毕竟是比较新的产品,如果能谈判成功的话,价格或许能比波生坦高一些。


曲前列尼尔可以与以上2类联用,日价格现在和马昔腾坦差不多,谈判成功可能性也不太大。本类产品本来上市的还有伊洛前列素,但厂家2015年计划逐步退出中国市场,所以估计不会参与本次目录。另外,PDE5类国际上其实也是一线药物,但国内全没有适应症,也没法参加评审。

 

2. C型尼曼匹克病


考虑到C型尼曼匹克病多数于儿童时期发病,发病率极低,但生存期也不长,麦格司他在谈判时可能还有些加成,难度在于现在日价格有点儿高,不过还是有一定概率能谈判成功。

 

3. 阵发性睡眠性血红蛋白尿&非典型溶血性尿毒症


依库珠单抗在国外大概50万美元/年,实在太贵了,而且从流行病学上来看,这2个适应症放在国内庞大的人口基数下,花费算下来将是天文数字,所以,除非打个1折以下,否则很难谈判成功。


4. 戈谢病和庞贝氏病


伊米苷酶、阿糖苷酶α是同一家公司的2个罕见病药物,按能查到的价格肯定都超过100万/年,但全国能查到不少地方谈判准入了,但谈判价格并未公开,有些地方应该是有财政和慈善补贴,本次国家谈判应该会在地方低价的基础上再降一些,难度也是不小。

 

5. 四氢生物蝶呤缺乏症


沙丙蝶呤当前价格超过30万/年,同上面2个产品,全国不少地方有谈判准入,国家谈判会进一步降低价格,另针对高苯丙氨酸血症的特医食品也有望上市,未来还可以期待医保覆盖部分特医食品。

 

6. 特发性肺纤维化


尼达尼布和在目录内的吡非尼酮一样是国际指南推荐药物,但现在日价格是吡非尼酮的2倍以上,通过谈判降价也是可以进入目录的。


7. 多发性硬化


特立氟胺和36个产品谈判进入目录的重组人干扰素β-1b一样是指南一线推荐,曾经国内是有着重组人干扰素β-1a和重组人干扰素β-1b,但都先后退出了中国市场,导致曾经一度患者无药可用,只能去国外购药或者选择二线药物。随着36个产品医保谈判,重组人干扰素β-1b重新回到了国内市场,而且现在患者还有了新的选择。从治疗角度来看,本品价格现在看比重组人干扰素β-1b稍高一点,谈判进入目录应该问题不大。


8. 血友病


艾美赛珠单抗这个产品还是不错的,但实在太贵了,国外价格高达40万美元/年,国内定价未知但是估计不会太低,而且从临床必须性角度来看,这个产品可能比起很多罕见病药物没有那么强,所以进入目录的可能性比较低。


9. 再生障碍性贫血


地拉罗司是口服的铁螯合剂,用于长期输血时防止铁质聚积,同类品种在目录内有去铁胺,按日费用算地拉罗司要稍微贵一些,但当前也有慈善,算下来也并不贵多少。同类还有去铁酮也没进目录,考虑到本类儿童患者居多,所以按日费用算价格也还可以。本类这2个产品小幅降价都有希望进入目录。

 

10. 儿童用药


拉布立海用于儿童白血病、淋巴瘤患者的尿酸水平控制,价格未知,但按常规推测估计不会很低,所以也得看谈判结果了。

 

其实国内上市的罕见病药物还有一些,但大多数在国内都还没有批准罕见病的适应症,比如依达拉奉用于治疗肌萎缩侧索硬化,或是他克莫司用于治疗重症肌无力。考虑现在医保的智能审核系统比较发达,虽然这些产品在目录内,但超适应症使用还是没法报销的,这点除非医保目录能有新的针对罕见病的规则解释,否则只能指望有厂家能注册下来罕见病适应症了。


◆  ◆  ◆结语


讲了半天,都在讲调入目录,实际上这次目录还涉及到部分产品的调出,很多人可能会联想到辅助用药,但是经过2017版目录的精简和适应症加限,现在保留在国家目录内的辅助用药已经并不多了,对照各省报上来的辅助用药数据,可以发现绝大多数辅助用药都是省级增补,或是在省级调整了适应症限制的产品。所以,除了少数辅助用药的调整,调出目录应该还会有一些老的缺乏循证证据、实际已经退市、没有厂家生产和销售的品种。特别是随着一致性评价和4+7的进展,很多更好的二代三代药物都已经到了地板价,那么自然就没什么必要在目录内保留那么多老的一代药物了。


另外,关于刚才说到省级增补辅助用药的问题,近期国家医保局在就医保目录管理的边界和调整权限征求意见,未来或许全国会统一成一个医保目录。如果是这样管理,那么毫无疑问有利于提高全国患者的公平性,也朝着未来动态调整和负面目录的管理方向更近了一步,但同时确实对于区域性的流行病学问题有些不足,还有之前有一些地方属于医保基金和财政方面都比较充裕,会提前额外增补或谈判一些罕见病产品的情况,这至少对这些罕见病药物留在市场上起到了积极作用,如果未来全国统一目录,那么对于谈判失败,但确实是一些救急救命的罕见病产品来说,可能厂家选择退出中国市场,最终患者无药可用,又会走上“药神”的道路。所以,如何权衡公平性和可及性,这确实是个难度非常高的问题,我们期待管理者和专家们的智慧,能够尽可能妥帖的制定出对策。

 

再往长远看一些,如果未来由国家统一管理目录,那么本次调整目录甚至有可能是最后一次大规模的医保目录调整,未来很可能会采取定期动态调整的方式来管理目录,比如每年定期针对新药做一次目录调整和谈判。甚至可以学习国外如NICE等评价机构,探索随时准入,或与药监审批联动准入。随着两次谈判完成,谈判资料基本上已经实现了标准化,未来只要在现有的基础上进一步完善即可。人员和专家方面,以国家医保局及下属事业单位的现有编制比较困难,未来或可以考虑仿照CDE,建立起一套固定的专家咨询委员会制度,对于参与医保评审的专家采取聘任制。建立起完备的制度流程后,就可以针对新药随时启动目录评审或谈判,并针对独家产品制定支付标准,而非独家产品的竞争品类可以交给地方制定,更多的参考市场价格。这也是考虑到毕竟目前基金统筹层次多数还保留在地级市一级,交由地方自行制定标准更有利于平衡基金收支。


对于医药企业来说,在行业“凛冬已至”的形势之下,本次医保目录调整无疑是带来了一股春风。本文仅对其中化药和生物制品的重点部分进行了简单的梳理,其他如消化、麻醉、眼科等品种一样有着准入机会,而中成药品种数量常规来说会比化药略少,最终预估整体调进调出的品种数量虽然可能会比2017版目录时略少,但要考虑到这仅仅是时隔2年的一次更新,而且可以预见的是,本次目录准入势必会更新大量创新产品,这无疑是对创新型企业一种切实的肯定和鼓励。


具体金额方面,虽然不能准确的计算出准确的数字,但根据官方公布的36种和17种药品谈判的基金负担金额来推算,本次目录新准入产品的医保年增支出保守估计也会在100亿以上,而与这个数字相比,行业谈之色变的4+7带量采购所能节省的医保基金应该还不到这个数字的一半。当然,这100多亿是建立在谈判降价基础之上的,但“就企业而言,纳入医保意味着广阔的市场前景,成长的收益远可抵消降价的损失”(注:此话源自陈金甫副局长)。从之前36种产品谈判的接近2年的销售数据来看,多数品种纳入医保后也确实是取得了销量的大幅增长,吃到了医保分享的蛋糕。


那么,对于医药企业来说,如何在未来吃到更多的蛋糕呢?特别是行业凛冬之下,有些企业可能少吃一口就面临着无法过冬的局面,特别是对于产品单一的初创企业来说,可能家底远不如一些老牌企业来的殷实,第一个产品医保谈判的成败,可能直接就是导致企业生死存亡的大问题。关于这个问题,我认为答案是“天时不如地利,地利不如人和”。无论是新药创制还是重要仿制,未来企业面对的是医保部门越来越专业化的准入要求。固然一些如产品自身属性,上市时间等天时地利的因素很重要,但及早的建立起专业的准入队伍,准确的把握政策形势更重要。大到如产品立项研发、引进等企业策略,小到医保谈判、招标议价等具体细节,让专业的准入人才更多的参与进来,才不至于让投入的研发资金或产品买断费用打水漂,同时,准入谈判时也更可能谈出好价格,为企业赚取更多合理利润。


最后再谈一些个人的体会。记得在2017年撰写《终极猜想 · 最有可能入围新版医保目录的品种分析》的时候,在文章末尾还吐槽创新药的准入似乎越来越慢,不想短短2年间,无论是从药监还是到医保,在准入环境方面竟然有了如此翻天覆地的变化。以此速度,几年内做到与国际接轨似乎也不是什么梦想。从患者的角度出发,能有更多的新药准入真的是很大的福音,特别是这次的目录评审重点也都是患者盼望已久的品类。


在撰写本文的时候,搜索一些品种时还能看到过去患者的帖子,主要都是围绕着2个话题,一是哪儿能买到,二是什么时候能报销。很多患者在分享一些去国外购药的渠道,或者是讲述因病致贫的故事,看着确实让人心里难过,希望以后这样的故事越来越少。医保目录从2000年至今,本次已经是第4次重大调整,每次调整都可以看出医保管理部门在目录管理方面从宏观到细节的各种进步,特别是最近2年的调整,更是加速了改革的步伐,朝着价值导向的医保战略购买的目标越走越快。本次是医保局成立之后的第一次调整,势必承担了新部门改革的重任和与之俱来的压力。按年前召开的全国医疗保障工作会议上提出的要求“回应社会解民忧,敢于担当推改革”。在此,我们可以对本次调整多一些期待,也预祝本次调整可以取得圆满成功。


机器翻译

According to the 2019 key work assignments of the National Medical Insurance Bureau, it is expected that a new round of national medical insurance catalogue adjustment will be launched in the near future. Referring to the progress of the 2017 edition of the catalogue, it is expected that the plan and basic database will be determined in March-April. Then, in May and June, the expert consultation and selection will be completed. From July to September, the medical insurance admission products will be negotiated. If all goes well, then the new medical insurance catalogue is expected to be released before the National Day and will be implemented during the year.

< p>Because this directory adjustment work time is tight, the task is heavy, and the time from the 2017 version of the catalog is not too long, so you can boldly guess: 1) the base database may use the 2017 version of the database when the directory is adjusted, and then join The 2017 version of the catalog database will be listed after the deadline for new drug data, which should focus on the innovative drug part. 2) should be a review of the province's supplementary and negotiated data as a reference. 3) expert library, due to the 2017 version of the country In the catalogue and provincial review, each province has established its own expert database, so it only needs to make a small update on the previous basis. Can be used directly.

As for the specific review program, whether the specific varieties can enter the catalogue, the general principle should be mentioned in the 2017 article "The ultimate guess, the most likely to be included in the new medical insurance catalogue" The clinical needs. Economic factors and market factors are not repeated here. There is no clear boundary between the catalogue and the negotiations mentioned in the previous paragraph. With the development of two rounds of medical insurance negotiations, it is now possible to deduce a general principle: The aspect should be an exclusive variety, and the vast majority are still in the patent period. On the other hand, it should be more expensive than the products in the same category or in the same therapeutic field. It is necessary to further negotiate to reduce the price. In addition, this catalogue The judging panel involves 11 non-medical national medicine products. Although the basic medicines and medical insurance catalogues are from two ministries, it does not mean that 100% of essential medicines should enter the medical insurance catalogue. However, there should still be a certain bonus in the judging.

According to the new drugs approved for domestic listing from 2016 to the present, from Pharmcube PharmaGo, although the overall number is still multinational The majority of innovative pharmaceutical products, but domestic companies have begun to have a lot of innovative products on the market, the number far exceeds the 2017 version of the catalog review, which is very encouraging progress. Although theoretically, medical insurance does not encourage domestic innovation. Obligations, but from the actual past experience, there will be some additional bonuses.

This article is mainly to make some analysis and prediction of some popular varieties in the 2019 national medical insurance catalogue adjustment, text According to the “Medical diseases such as cancer, chronic diseases, rare diseases and children's medications” highlighted in the key tasks of the National Medical Insurance Bureau, we have made a simple classification. Please also give us valuable comments.

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Diabetes medication

1. Insulin

There are still heavy products that are not included in the catalogue only De Gu insulin, from Degu insulin currently From the perspective of pricing strategy, it seems that it is necessary to enter the catalogue directly, so the probability will be directly entered into the catalogue without any negotiation. (

2. GLP-1 class

Considering Liraglutide has been negotiated into health care in 2017, In the second adjustment, exenatide. exenatide sustained-release microspheres. Lisinide. Durapeptide and domestic benaglutide are expected to enter the catalogue. Among them, exenatide is actually listed in China. GLP-1, but did not pass the expert selection when adjusting the catalogue in 2017. There may be problems with the transfer of domestic sales rights at that time, or it may be due to the two doses per day and relatively high from the perspective of the product itself. The price has formed a certain obstacle. The current price of exenatide will still be higher than that of liraglutide, but the sustained release microsphere dosage form is more expensive, but it wins once a week. Compliance. Domestic benaglutide is 3 times a day and the current price is the most expensive. It is estimated that the price of the drug will be greatly reduced. However, the nisin peptide and the glucosinolate can not be found at present.

< p>Anyway, no matter which GLP-1, at least the current laraglutide as a reference for payment standards, it is expected that the price after negotiation will not exceed 40 yuan / day, of which exenatide sustained release microspheres and degrees Lactopeptide is used as a long-acting once-a-week preparation. Can be slightly higher. My personal expectation of somaglutide and its oral preparations, from the review progress, certainly can not catch up with this catalogue. Also can not catch up with the possibility of major special support of polyethylene glycol Senamin.

Indications for this class of drugs should refer to liraglutide, the more expensive the product may be more restrictive.

3. SGLT-2 inhibitor

There are five DPP-4 drugs in the 2017 version of the catalogue, this time Daglipex. Engliflin. The three SGLT-2 inhibitors of Cagliflozin are very promising to enter the catalogue. The only problem is that the price of DPP-4 is less than 10 yuan per day. In contrast, the price of SGLT-2 inhibitors is still slightly higher. Maybe some products will start negotiations. Dagley’s actual daily cost is the lowest. The national base drug addition is the most likely to enter the catalogue directly. The indications for this category should refer to DPP-4, which is limited to second-line medication.

4. Compound product

Of the five DPP-4 inhibitors that entered the 2017 edition, four of them were marketed with metformin, and the SGLT-2 was also listed on the Metformin compound. This is undoubtedly because metformin is the absolute first-line drug for the treatment of diabetes. Internationally, both DPP4 and SGLT2, the sales of metformin compound products are not bad. For chronic diseases such as hypertension or diabetes, which can be used in combination, the compound products can be Improve patient compliance. But for the domestic medical insurance catalog review, how to pay for metformin in the compound product is the key.

At present, even the original research price of metformin is not too expensive, the day The cost is only about 3 yuan, not to mention that metformin is definitely the second batch of countries to purchase the variety, the time will definitely be less than 1 yuan or even 0.5 yuan. So, for these compound products, if similar to foreign The pricing strategy for the purchase of adjuvant drugs (Note: For example, the price of Englenet is only for the price of Englenet), it is the right choice to enter the product as soon as possible. In particular, several patents are about to expire. The product may also be able to delay the patent cliff brought by the national procurement through the exclusive compound product. From the current According to the data, metformin in the sitagliptin compound is the cheapest, and may be more active than other products, and the enclave compound may be more difficult due to the short time to market. Indications limit will be equivalent to the main drug.

5. Others

The current domestic GLP-1.DPP-4.SGLT-2 has a lot of research products, from the current Judging from the progress of the review, it is estimated that it will not be able to catch up with the medical insurance catalogue review. Among them, it is worth mentioning that the relatively long-term DPP-4 inhibitor troglitazone has been fried in the past few days. This product is domestic. Some problems in patents, these two years are also the hottest domestic imitation declarations. But calm analysis, long-acting DPP4 including troglitazone and alogliptin, only listed in Japan worldwide, of which augretine is in In Europe and the United States, 9 phase III clinical trials were enrolled in more than 7,000 patients, and the market was finally abandoned. On the one hand, the product itself was safe. Compliance and other reasons, on the other hand, the price and medical insurance payment.

The ultimate goal of future domestic health insurance is to implement value-oriented strategic purchases. According to this established goal, regardless of the form of management of the future medical insurance drug list, the focus should be on the comprehensive consideration of real clinical value and price. Domestic companies, whether they are innovative or imitation, should carefully consider their product pipelines and profit expectations. Quglitin will be listed in the future. Medicare payments and market prospects will be a good example, but in If this space is limited, it will not be carried out too much. If you have the opportunity, you may be able to open a single article to talk about.

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Cardiovascular Drugs

1. LCZ696

Shakuba Qusarsar is one of the hottest changes in the medical insurance catalogue. The only problem is the price. The domestic price of this product is slightly lower than that of the US. Some, but it is too expensive compared to other heart failure drugs. If you calculate according to the latest winning price, the daily cost is as high as 56 yuan. For reference, the 2017 version of the new heart disease new drug ivabradine The daily cost is only 17.3 yuan. Therefore, although this product is However, the probability of entering the catalogue is very large, but the probability of negotiating the price cut is also quite large. Depending on the outcome of the negotiations, this product may be subject to indications. If it is limited to second-line medication, it is limited to other heart-failure drugs. Tolerance will be more harmful.

2. PCSK9

There are only Yiluo's monoclonal antibodies currently marketed in this category, but alimizumab obtained CDE two weeks ago. The priority of review, perhaps also catch up with the last bus before the deadline. In terms of efficacy and practical clinical significance, PCSK9 is a good category, after all, the probability of clinical statin intolerance is about 15%, but with the above sand Like Kubba 缬沙沙坦, even in the case of foreign medical insurance payments relative to domestic easing, relatively high pricing has caused a lot of payment pressure on the payer. This is actually very well understood, although the innovation target is compared with the traditional The mature treatment plan is slightly improved, but the price is up to 10 times. Any payer will carefully verify whether the evidence of pharmacoeconomics is sufficient. In view of this, there is still a big doubt about whether this category can enter the catalogue this time. Even if It will also be under the premise of negotiating a large price cut, plus the indications for statin intolerance.

3. Compound products

Tilmisartan amlodipine. Mesalamine amlodipine. Perindopril amlodipine. Amlodipine folic acid... Don't be surprised, in the past two years, there have been so many amlodipine compound preparations on the market. On the one hand, amlodipine itself is good. Efficacy. Safety and half-life, there are more compound products of amlodipine in the world. On the other hand, there should be some Chinese characteristics. Different from the international use of antihypertensive drugs with ACEI and ARB, China market share The largest category is CCB, the largest of which is amlodipine.

The more distinctive of these products is perindopril amlodipine, after all, ASCOT research is the most in the past two decades. One of the classic cardiovascular clinical studies, the main drugs used are perindopril and amlodipine, which is undoubtedly the most adequate evidence from the evidence-based evidence. The olmesartan amlodipine may follow the Austrian Mesacitrate mono- and olmesartan medoxorate The same indications for thiazide are more restrictive than other ARBs. The price of amlodipine folic acid is not yet available, but because it is the same manufacturer as enalapril, the estimated price is not too low. Enalapril as a domestic innovation, the price is more expensive than the original research, but also entered the medical insurance catalog very early, so the amlodipine folic acid is even more expensive, as long as the price is too far from the price of the treatment, it should still Can enter the catalogue.

Speaking of cardiovascular compound products, there are two earlier classic products that are expected to enter the catalogue this time, one is perindopril and the other is sim Ruthatin ezetimibe, these two products have also been added to the provincial directory in most parts of the country.

This is the time for the State Council 2019 government work task, the article mentioned "doing common Prevention and treatment of chronic diseases, including hypertension, diabetes and other outpatient medications into medical insurance reimbursement.", it can be understood that the previous high blood pressure and diabetes products are expected to receive additional bonuses in this catalogue, relative quota restrictions are expected to be looser, will enter more production Product.

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Central nervous system diseases

1. Psychiatric medication

Bunanlin and lurasidone, the same company Two new anti-schizophrenia drugs have been listed in one breath, and they still have certain characteristics. The price of Bunan Selin is not too expensive. Lurasidone can not find the price now, but it should not be too Expensive, these two products have great hopes to enter the catalogue. Fusulfacetin is known as a new generation of antidepressants, and the products do have some characteristics, but in fact, compared with the products in the catalogue, What is too big a advantage, and this product is too expensive to look at the price of the winning bid that can be queried now. It is estimated that the catalogue price will be greatly reduced. Although the psychiatric products seem to be relatively small, from the perspective of medical insurance catalogue There has always been an extra bonus, non-medical products are relatively few, and the restrictions are relatively small.

2. Neurology medication

The Parkinson's disease field has not been listed in the past two years. Less new drugs, first of all the second generation MAO-B inhibitor rasagiline, the biggest problem of this product is more expensive, than in the eyes The first generation of selegilan is more than 10 times. Of course, the efficacy of rasagiline is also quite good. Many patients in China are eating the Indian version before going public. If this price can be lowered into the catalogue, it is undoubtedly a patient. Gospel.

The other is the newly listed rotigotine patch. Parkinson's patients tend to have poor compliance. The transdermal patch for external use of the drug can undoubtedly improve patient compliance. It should be said that it is also very distinctive. The problem with the catalogue is the same as that of Rasagiran. If you want to use a full dose, it will be similar to the cost of Rasagiran. It is also more expensive. See if there is negotiation. Opportunity.

Entacapone Double Dopa is a three-way compound drug, unilaterally in the catalogue, the compound can improve compliance, the price is also OK, theoretically no problem, but Parkinson is a little niche in this area. It is a problem to enter the expert field of vision.

The anti-dementia field has also launched a new clearing skin sticker. The oral dosage form of this product is called rivastigmine. Is already in the catalogue, it is estimated that the future drug regulatory agencies will put the general Uniform. Anti-dementia 4 first-line drugs are actually in the catalogue, 2017 catalogue also added the Donepezil orally disintegrating tablets, so I feel that Liss's clear-cut skin is also very popular, especially now it seems pricing Not too expensive, and the imitation products are also on the market soon.

The field of epilepsy has newly added lacosamide (Lacamide). Since it has just been listed, the pricing is still unclear. If the pricing is reasonable, The probability of entering the catalogue is quite large, especially the imitation products are also on the market. Here, I feel that there are so many epilepsy drugs in the alphabet, and there will be bovistam in the future. It is easier to have children's indications. , but this time is too late.

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Respiratory Medicine

Omalizumab is the world's first approved treatment for moderate to severe asthma. Targeted therapeutic drugs, the product is very good, but the wife is too expensive, the cost of 100,000+ treatment, not low incidence, even if you can negotiate to reduce part of the price, it is not very optimistic about the medical insurance fund can afford this product

Indigo Trogmonium Bromide. Ume Ammonium Bromide Rantero. Tiotropium bromide Odatrol. Fluticasone citrate Virantro. Odattro, most of the current price data can not be found, this category is generally not too expensive to enter the catalog, the price Dimensions can be found in the 2017 new catalogue of 茚达特罗.

Beidaquinoline. Dramani is a new anti-tuberculosis drug. These two products can be said to be currently resistant. The last line of defense for multidrug tuberculosis, but it is hard to say whether the medical insurance will cover these two products.

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Tumor and major disease drugs

1.PD-1

After 20 anticancer drug negotiations in 2018, The most popular products that are not in the catalog are undoubtedly PD-1. The current market is Navulitis Monoclonal Antibody (O Drug). Pabolizumab (K Drug). Treipril Monoclonal. Lizumab, and Carrefour and Tirizumab may also catch up with the last bus.

From the perspective of negotiating into the catalogue, it should be said that every family has the possibility of success. There is also the possibility of failure. First of all, it is basically clear that the negotiation will be based on the indications. If a product has been approved for multiple indications at the time of negotiation, the result of the negotiation is likely to be based on only one. Indications, and medical insurance payment restrictions will strictly follow the one indication, the latter indications are equivalent to non-medical insurance, that is, although the overall market potential of PD-1 is great, this medical insurance negotiation payment Only a small part of it will be involved.

In terms of the price dimension of reference, the international price is of little significance, and the domestic price of O medicine K medicine is lower than that of foreign countries, while others There is no price and no price in foreign countries. Charity prices will be referred to. The most important thing is to consider the efficacy and price, which is compared with traditional therapy, including first-line chemotherapy and the targeted drugs that are now in the catalog. It will also make horizontal comparisons between different PD-1 products. Therefore, although the final price is not as bad as a few hundred yuan, it is necessary to do a good job of sharply lowering the price relative to the existing price. In the case of medicine K, it is the lowest in the world to accept Chinese prices, and for domestic companies, it is also necessary to make a few folds of the existing “low price”.

Consultation results In contrast, I personally are more optimistic about foreign companies. After all, from the perspective of the adequacy of clinical evidence, or from the perspective of negotiation preparation and professionalism, foreign companies are obviously better. From the two rounds of historical negotiations, Basically, the products that failed to negotiate are in two cases. One is that the price negotiated by foreign companies is far lower than the international price. Especially for products with a longer patent period, the decline is unacceptable. The other is a small number of foreign companies and Domestic enterprises, due to the lack of clear pricing strategies and professional talents, are in a completely passive situation during negotiations.

In particular, since the development of medical insurance negotiations, the professionalism and experience of medical insurance companies are constantly growing, that is, "We have a stronger voice in the medical insurance negotiations." (Note: This is from Director Hu Jinglin). At this time, domestic companies will send some amateur players to play, although these amateurs may be among the other in business or sales. But suppose the negotiating table is a football field. This is basically the same as sending China Guoping to play with the French national football.

According to the information collected by Pharmcube Global New Drugstore NextPharma, PD-1/PD-L1 It can be said that it is the hottest target in the world, and the related projects have reached 173. Even if most of the products eventually die, more than 10 products will be listed in the next year, and the medical insurance can completely adopt the strategy of testing the water this year. In the next round of negotiations, the scope of the indications will be expanded and the prices will be greatly reduced. At that time, the grand occasion may be comparable to last year's 4+7 purchases. Although the outcome may be compared for enterprises. Cool, but for the medical insurance, you can achieve a true value-oriented strategic purchase, and for every insured person or ordinary people, we are all beneficiaries.

2. Her2. CDK4/6

Her2 target currently has clinically significant indications for breast cancer. Pertuzumab can be considered an upgraded product of trastuzumab. The main advantage of pyrrolidine is oral Small molecule drugs, and can alleviate the adverse reactions of diarrhea, both products can be combined with trastuzumab to further improve the survival of Her2-positive patients. Pipercilil is applied to HR+/Her2 by inhibiting CDK4/6 - Breast cancer patients are breakthrough improvements based on traditional aromatase inhibitors. From the perspective of clinical needs, these three products have sufficient reasons, as long as the price negotiation link can pass, the entry into the catalogue is not a big problem.

3. PARP

Olapali is currently the only listed PARP inhibitor in China. Other similar products are unable to catch up with the progress. The targeted drug for ovarian cancer is currently one. There is little problem in entering the negotiation process, and the price may be Based on the existing charity, there are some more.

3. ALK

Alitinib has been approved, and the second generation ALK's Enthatinib has won the CDE priority. Eligibility for review may also catch up with the last bus. Considering the generation of ALK crizotinib, the second generation of ALK sirinib has been negotiated in 17 anticancer drugs, so the price of these two products has also been referenced. Interval, entering the negotiation process is not a big problem.

4. VEGFR

Fuqualinib is a domestically-targeted drug that has been listed late, and the indication is colorectal cancer. The main competing product is bevacizumab, the price is also referenced, and the probability of negotiating access is estimated to be very high. Absolute intraocular injection reference products are ranibizumab and Compaqip, the current pricing is only The reference product is a bit more expensive, and the probability of negotiating access is very high. The current indication for rivastatinib is only liver cancer, and the reference product is probably Riggo. Nie, the current pricing is slightly more expensive, but there is charity. It is estimated that the negotiation can be entered into the catalogue around the charity price. The most similar to Lunvainib is actually the protagonist of the recent "fake medicine" incident, Cabotinib, but the original research seems to have no China's listing plan, domestic imitation certainly must not catch up with this catalog review.

5. Gnrh receptor antagonist

Gerekic This product is similar to already in the catalogue Goserelin implants or leuprolide microspheres are long-acting drugs for the treatment of hormone-dependent prostate cancer, but with slight improvements, so the problem of entering the catalogue is small, and the price may be better than Goscher Lin implants are slightly more expensive.

6. Alkylating agents

Melpentine injections are nitrogen mustards, oral dosage forms are already in the catalog, and injections are safe. In fact, there is improvement. Bendamustine injection is a bifunctional alkylating agent that combines the characteristics of nitrogen mustards and nitrosoureas, both of which are mostly in the catalog. These two products As long as the price is not too expensive, the problem of entering the catalogue is not big, but the two companies are relatively small, and the product awareness rate is

7. Taxanes

Paclitaxel liposomes, the first negotiation failed, the second negotiation rejected the invitation, this time I don’t know if there is still a chance There is also paclitaxel albumin, which has not been selected by experts before. Eighty percent is still too expensive and exclusive, but now there are two generic products on the market, and the possibility of entering the catalogue has increased greatly. From the perspective of efficacy safety These two products have undoubtedly improved significantly compared to ordinary paclitaxel, but the price will still play a decisive role in the question of whether or not to enter the catalogue.

8. Others

P Leshafu is used for stem cell transplantation and is an orphan drug abroad. However, the concept of orphan drugs abroad is not the same as the concept of rare diseases in China, so it is estimated that it will not participate in the review as a rare disease. Domestic pricing is unknown, but because foreign countries are Orphan drugs are more expensive, so there is some doubt about whether you can significantly reduce the price into the catalogue.

Rucotinib is used to treat myelofibrosis, the only product that failed when 17 anticancer drugs were negotiated. Because the negotiated price is lower than the foreign price, this time is not I know if I can give another chance. Even if I can give the opportunity, the negotiation will be more difficult. The good thing is that there is no other drug for this indication, and after all, the first negotiation of cetuximab failed but the second time. Successful examples, so there will still be a small probability to talk about success.

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Hepatitis C Drugs

According to China's Hepatitis C Prevention Guide 2015 Edition According to the disease data, HCV1b and 2a genotypes are more common in China, with 1b type (56.8%), followed by type 2 (24.1%) and type 3 (9.1%). No genes type 4 and type 5 were found. Type 6 is relatively small (6.3%). Mixed genotypes are rare (about 2.1%), mostly genetic type 1 mixed type 2.

So, according to the company's products to differentiate the program, Dala Veashurivir (type 1), Obi Pali desebuvir (type 1), albavir gravivir (type 1.4), domestic danoribe (type 1) can actually be assigned to the same The file, while the sophos-Pebuvir and its combination preparations can be single-segmented, sophos-brevevivistavir (full-genotype) is one of the most able to fight, not to mention the base drug addition, The probability of the catalogue is very large.

This category is highly competitive, and the first file can cover more than half of the patients, so it is possible to talk about products that use low-cost strategies. The probability is not great, the price of Sopho-Beauvirone is also the key, because it will definitely be higher than the first gear, so it also infers the price of the first gear.

The fierce competition in this category also stems from the fact that this negotiation is related to the first wave of medical insurance patients in China. Because the disease can be cured, foreign experience shows that who can get medical insurance payment at the right price and grab the first few patients. You can win most of the market, and the final market is almost close to disappearing. So, if you can't catch up with this negotiation, such as Ravi Davi, the market that will be harvested in the future will be very small. In addition, West American River Although it is approved in China, it is basically equal to delisting. In fact, it is also an option. After all, for multinational companies, although the domestic market is large, if the output is less than the investment, it is better to give up, but for a large number of domestic research products. In fact, it is really unknown whether the cost can be recovered in the future.

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AIDS drugs

1. Integrase inhibitors

Dotivide and combination preparations of dobramide (Dotivide abacavir Lamivudine), ralivide, aceviride combination formulation acecoin (Ai Villeve Cobbistatin, which is a product of flunarbutamol, does not know if there are any products available. Achieving a breakthrough in the integration of integrase inhibitors in the medical insurance catalogue, most of the first-line treatment programs in the world contain integrase inhibitors, but the domestic price is limited to the short-term price is basically not expected to enter the free drug list. From the perspective of treatment costs, ralivide It has been close to the enoxopabine tenofovir in the catalogue, but AIDS treatment often uses several types of drugs. The entry of a relatively expensive drug into the catalog will impose an additional burden on the fund, so it may still be difficult.

< p>2. Long-acting fusion inhibitors

Aboweitai is a domestic innovative product, once a week, but the current price is still relatively expensive, it is estimated to be reduced to about half of the catalogue, and high-end oral drugs Quite a level. The short-acting enfuvirtide in the same species is in the catalogue, but it seems that the country is out of stock. The price of the winning bid can be found in the sky. There is no reference significance.

3. Protease inhibition Agent

Daranawei Cobbistat, the new listing of enhanced, the price is also expensive, consider the arrival of Lunawei is not in the catalog, feels awkward. The same variety of Shaku Nawei in the catalog, But the original research stopped importing, the country has There is no valid approval.

4. Nucleoside and nucleotide reverse transcriptase inhibitors

Entropitabine propofol tenofovir, said this product is connected Propofol is a single drug here. It is said that propofol is a famous TAF, which is a prodrug of tenofovir disoproxil (TDF), so the theoretical indication can be hepatitis B. And AIDS, but the domestic unilaterally approved only hepatitis B, and the combination of emtricitabine and integrase inhibitors are AIDS. The price is now unknown, foreign is not cheap, and domestic tenofovir disoproxil At 4+7, it is already a few cents of floor price, so I feel that the series of propofol forefovir is more difficult to enter this catalogue, unless the manufacturer can give a very favorable price, such as reference to the authorized imitation of India. Price.

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hematology drugs

Aidosaban can refer to rivaroxaban or dabigatran etexilate, the price is not too Expensive words should be able to go directly into the catalog, indications will also be limited to atrial fibrillation. edabetauzumab is a reversal agent of dabigatran etexilate, the price is unknown, but guess It is more expensive, and it is slightly less popular. It is hopeless to enter the catalogue.

The indication for atratropipin is primary immune thrombocytopenia (ITP), and the reference drug TPO is the new entry category of 2017. Products, medical insurance restrictions also have ITP, so as long as the pricing and TPO are close, entering the catalog should be a problem. Rossa, referring to the drug EPO, is estimated to limit renal anemia, as long as the price and EPO are close, entering the catalog should be a problem Not big.

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Children with rare diseases

1. Pulmonary hypertension

Bosentan failed to negotiate in 2017 However, after entering the basic medicine last year, generic drugs are also on the market. As long as they no longer make mistakes in the negotiations, this catalogue hopes to be very big. An Lishengtan has entered many provincial catalogues through the failure of Bosentan negotiations. The effect and price are similar to Bosentan, and the hope is also great. Matthew Tentan is an upgraded version of Bosentan, but the price is too expensive, and it is a bit difficult to negotiate.

Leocarbin is different from the above three endothelin receptor drugs and can be used in combination. The daily price is probably about the same as that of Bosentan. But after all, it is a relatively new product. If it can be negotiated successfully, the price may be higher than that of Bosentan.

The frontline can be combined with the above 2 categories, the daily price is now and the Matthew Tan is almost the same, the possibility of negotiation success is not too big. This product is also listed on the market is also Iloprost, but the manufacturer plans to gradually withdraw from the Chinese market in 2015, so it is estimated that will not participate in this catalog. In addition, PDE5 international In fact, it is also a first-line drug, but there are no indications in the country, and it is impossible to participate in the review.

2. Niemann's disease type C

Considering that type C Niemann's disease is mostly In childhood, the incidence rate is extremely low, but the survival period is not long. Magmeste may have some bonuses during the negotiation. The difficulty is that the price is a bit high today, but there is still a certain probability that the negotiation will be successful.

3. Paroxysmal nocturnal hemoglobinuria atypical hemolytic uremia

Eculizumab is about $500,000 per year abroad, which is too expensive and epidemiological From the above point of view, these two indications are placed under the huge population base in China. Figures, so unless it is less than 1%, it is difficult to negotiate successfully.

4. Gaucher disease and Pompe disease

Imidonase. Aglucosidase It is two rare disease drugs of the same company. According to the price that can be found, it must exceed 1 million/year. However, many places in the country can be negotiated for entry, but the negotiated price is not open. Some places should have Financial and charitable subsidies, this national negotiation should be reduced on the basis of local low prices, the difficulty is not small.

5. Tetrahydrobiopterin deficiency

The current price of sapphire is more than 300,000/year. With the above two products, there are many places in the country with negotiation access. The national negotiations will further reduce the price, and the special medical food for hyperphenylalaninemia. It is also expected to go on the market. In the future, you can expect medical insurance to cover some special medical foods.

6. Idiopathic pulmonary fibrosis

Nidanib and pirfenidone in the catalogue The same is the international guide recommended drugs, but now the price is more than twice the price of pirfenidone, negotiated price reduction can also enter the catalog.

7. Multiple sclerosis

Rifamine and 36 products are negotiating into the catalogue of recombinant human interferon beta-1b, which is the first recommendation of the guide. It used to have recombinant human interferon beta-1a and recombinant human interferon beta-1b, but both have withdrawn from China. In the market, once the patient was once drug-free, he could only go abroad to buy medicine or choose second-line drugs. With the negotiation of 36 products, the recombinant human interferon β-1b returned to the domestic market, and now patients have new Choice. From a therapeutic point of view, the price of this product is now slightly higher than recombinant human interferon beta-1b. One point, the negotiation into the directory should not be a problem.

8. Hemophilia

Emmy Safranizumab is a good product, but it is too expensive, foreign prices are high US$400,000/year, domestic pricing is unknown but it is not expected to be too low, and from a clinical necessity point of view, this product may not be as strong as many rare disease drugs, so it is less likely to enter the catalogue.

9. Aplastic anemia

Dalrosone is an oral iron chelator that is used to prevent iron accumulation during long-term blood transfusion. The same species has deferoxamine in the catalogue. The cost is calculated to be slightly more expensive, but there are also charities at present. It is not too expensive to calculate. The same kind of deferiprone is not included in the catalogue. Considering the majority of children in this category, the price is also calculated according to the daily cost. Also. The small price cuts of these two products are expected to enter the catalogue.

10. Children's medication

Lab Lihai is used for childhood leukemia. Uric acid levels in patients with lymphoma Control, the price is unknown, but the conventional estimation is not very low, so it depends on the negotiation results.

There are some rare drugs listed in China, but most of them have not approved indications for rare diseases in China, such as edaravone for the treatment of amyotrophic lateral sclerosis, or tacrolimus for the treatment of myasthenia Powerless. Considering that the smart audit system of medical insurance is relatively developed now, although these products are in the catalogue, the use of hyperindications is still not reimbursed. Unless the medical insurance catalogue has new rules for rare diseases, it can only be expected. Some manufacturers can register for rare disease indications.

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Conclusion

Speaking for a long time, they are all talking about the directory, actually this The sub-directory also involves the recall of some products. Many people may associate with the auxiliary drugs. However, after the 2017 version of the catalogue has been streamlined and the indications are limited, there are not many auxiliary drugs in the national catalog. The supplementary medication data reported can be found that most of the supplementary medications are provincial supplements, or products that have been adjusted for indications at the provincial level. Therefore, in addition to the adjustment of a small number of supplementary medications, there should be one The old lack of evidence-based evidence. Actually has been delisted. There are no varieties produced and sold by manufacturers. Especially with the consistency evaluation and 4+7 progress, many better second-generation and third-generation drugs have already reached the floor price, so naturally There is no need to keep so many old generations of drugs in the catalogue.

In addition, regarding the issue of supplemental supplemental drugs at the provincial level, the National Health Insurance Bureau recently agreed on the boundaries and adjustments of medical insurance catalogue management. Soliciting opinions, the country may be unified into a medical insurance catalog in the future. If it is managed in this way, it will undoubtedly help to improve the fairness of patients across the country, and it will be a step closer to the future dynamic adjustment and management of negative catalogues, but at the same time Indeed, there are some shortcomings in regional epidemiological problems. There are some places where the health insurance fund and the financial sector are relatively abundant. Some rare disease products will be added or negotiated in advance, at least for these rare diseases. The market has played a positive role. If the national unified catalogue is in the future, then the negotiations will fail, but it is indeed some emergency. For life-saving rare disease products, manufacturers may choose to withdraw from the Chinese market. In the end, patients will have no medicine to use, and they will embark on the path of “medicine gods.” Therefore, how to weigh fairness and accessibility is indeed a very difficult one. Question, we look forward to the wisdom of managers and experts, and be able to formulate countermeasures as far as possible.

Let's look at the long-term. If the catalogue is managed by the state in the future, then this adjustment catalog may even be possible. It is the last large-scale medical insurance catalogue adjustment. In the future, it is very likely to adopt a regular dynamic adjustment method to manage the catalogue. For example, it will make a catalogue adjustment and negotiation for new drugs every year. You can even learn from overseas evaluation institutions such as NICE to explore access at any time. Or with the drug supervision and approval linkage access. With the completion of the two negotiations, the negotiation materials have basically achieved standardization, as long as the existing foundation can be further improved. Personnel and experts, the National Health Insurance Bureau and its subordinates The existing establishment of the public institution is more difficult. In the future, it may be considered to follow the CDE and establish a fixed set of expert advisory committee members. The system adopts the appointment system for the experts who participate in the medical insurance evaluation. After establishing a complete system process, the catalogue review or negotiation can be initiated at any time for the new drug, and the payment standard is set for the exclusive product, and the competitive category of the exclusive product can be handed over to the place. Formulate, more reference to the market price. This is also considered that after all, the current fund pooling level is still retained at the prefecture-level city level, and it is more conducive to balance the fund revenue and expenditure by local self-developing standards.

For pharmaceutical companies, under the situation of “winter in the winter”, this medical insurance catalogue adjustment has undoubtedly brought a spring breeze. This article only briefly combs the key parts of chemical and biological products. Others such as digestion, anesthesia, ophthalmology and other varieties have the same access opportunities, and the number of proprietary Chinese medicines will be slightly less than the chemical, and the final estimate of the number of varieties transferred may be slightly smaller than the 2017 version. Less, but to take into account that this is only a two-year update, and it is foreseeable that this directory access will inevitably update a large number of innovative products, this Suspect is a practical affirmation and encouragement for innovative companies.

In terms of specific amount, although the accurate figures cannot be accurately calculated, according to the officially announced fund burden of 36 kinds and 17 kinds of drugs negotiated According to the amount, the conservative estimate of the annual increase in medical insurance for new access products in this catalogue will be more than 10 billion, and compared with this figure, the industry will talk about the 4+7 volume of purchases that can save the medical insurance fund. It should not be half of this figure. Of course, this more than 10 billion is based on the negotiation price reduction, but "in terms of enterprises, the inclusion of medical insurance means a broad market prospect, and the growth of income can offset the loss of price reduction. "(Note: This is from Chen Jinyu, deputy director). From the sales data of the previous 36 kinds of products negotiated for nearly 2 years, most of the varieties have actually achieved a substantial increase in sales after they were included in the medical insurance, and they have eaten the cake shared by the medical insurance."

So, for pharmaceutical companies, how to eat more cakes in the future? Especially in the winter of the industry, some enterprises may face a situation in which they can't spend the winter when they eat less. Especially for a single start-up enterprise, the bottom of the company may not be as good as some old-fashioned companies. The first product medical insurance negotiation The success or failure may directly be a big problem that leads to the survival of the enterprise. On this question, I think the answer is "the weather is not as good as the land, the land is not as good as the people." Whether it is new drug creation or important imitation, the future enterprise is facing the medical insurance department. The more specialized access requirements. Although some factors such as the product's own attributes, time to market and other factors are important, but the establishment of a professional entry team early, accurate grasp of the policy situation is more important. Introduce and other corporate strategies, as small as medical insurance negotiations. Specific details such as bidding and bargaining, so that professional entry talents can participate more, so as not to let the investment in R&D funds or product buyouts float, and at the same time, access It is also more likely to negotiate good prices during negotiations and earn more reasonable profits for the company.

Let's talk about some last. I remember that when I wrote "The Ultimate Conjecture · The most likely to be included in the new version of the medical insurance catalogue analysis" in 2017, the entry of innovative medicine at the end of the article seems to be getting slower and slower, not wanting to be in just 2 years, whether it is From drug supervision to medical insurance, there has been such a drastic change in the access environment. At this speed, it is not a dream to be in line with international standards within a few years. From the patient's point of view, there can be more new drugs. Entering the truth is a great gospel, especially the focus of this directory review is the category that patients have long been looking forward to.

At the time of this writing, you can see past patients when searching for some varieties. The posts are mainly around two topics, one is where to buy, and the other is when to reimburse. Many patients are sharing some channels to buy drugs abroad, or telling stories about poverty caused by illness, watching It’s really sad, I hope that there will be fewer and fewer stories in the future. The medical insurance catalogue has been the 4th major adjustment since 2000, and every adjustment can be seen in the medical insurance management department. The various aspects of the progress from macro to detail, especially the adjustment in the last two years, have accelerated the pace of reform, and the goal of purchasing a value-oriented medical insurance strategy has become faster and faster. This is after the establishment of the Medical Insurance Bureau. The first adjustment will inevitably bear the heavy responsibility of the new department reform and the pressure to come along with it. The request put forward at the National Medical Security Work Conference held before the year “Respond to the social solution to the people and dare to take the reform”. We can expect more from this adjustment, and I wish this adjustment a complete success.

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