Nedosiran

iStock, Love Employee As multiple companies vie to expand on Alnylam’s success in commercializing RNAi therapeutics, the pioneering company has set a goal of targeting small interfering RNA to any organ by 2030. In March, Alnylam chalked up two FDA approvals, for Amvuttra in transthyretin-mediated amyloidosis and, with Sanofi, Qfitlia in hemophilia A and B. Such approvals have become par for the course for Alnylam, leading multiple other companies—including GSK , AbbVie , Boehringer Ingelheim and Eli Lilly —to follow suit in pursuing therapies based on small interfering RNA (siRNA). And it’s not just the number of companies involved that’s expanding: while all siRNA therapies approved so far target the liver, Alnylam and others are now seeing some success in targeting other organs as well. The past two years have seen billions of dollars change hands in a bid to be part of this rapidly growing field. In January 2024, for example, Boehringer Ingelheim announced an agreement potentially worth more than $2 billion with Chinese biotech Suzhou Ribo Life Science and its Swedish unit Ribocure Pharmaceuticals to develop siRNA-based treatments for nonalcoholic or metabolic dysfunction-associated steatohepatitis (MASH), a disease expected to afflict 27 million Americans by 2030. And just last month, GSK plunked down $1.2 billion for Boston Pharmaceuticals’ investigational FGF21 analog efimosfermin alfa, also targeting MASH. “I think the siRNA space, for rare disease predominantly, has been revolutionary in a handful of cases,” said Myles Minter, a senior biotech analyst at William Blair. “And I do think that the large promise of the field to go into broader, more prevalent indications and to get more approvals is largely ahead of us.” A Genetic On/Off Switch The term RNA interference dates back to a 1998 paper by Craig Mello and colleagues, who found that double-stranded RNA was more effective than single strands in silencing genes with corresponding sequences in C. elegans . The mechanism turned out to also work in mammalian cells , and in 2002, multiple researchers who’d led key studies of the phenomenon, including Mello, teamed up with investors to found Alnylam. It took 16 years to gain FDA approval for the first siRNA drug, Onpattro, for polyneuropathy of hereditary transthyretin-mediated amyloidosis, a rare genetic disorder caused by mutations in the transthyretin ( TTR ) gene. One challenge Alnylam faced in the intervening years was in designing siRNAs that could escape degradation within the body for long enough to be effective, explained Vasant Jadhav, the company’s chief technology officer. But the biggest hurdle—one not unique to siRNAs—was getting the nucleic acid payloads where they needed to go. Then, in 2014, Alnylam researchers and their academic colleagues reported that linking siRNAs with a ligand called GalNAc would get them into cells in the liver, but not into other organs. Onpattro, approved in 2018, is a GalNac-linked siRNA. The drug “was pretty revolutionary at the time,” Minter said, because rather than simply treating symptoms or even slowing the toll of polyneuropathy of hereditary transthyretin-mediated amyloidosis, it elicited functional improvement. “The way I like to think about siRNA is that it’s a way that you can titrate, so you can dose at a genetic level. And it’s really one of the only modalities that you can do that with,” Minter told BioSpace . Other therapies followed from Alnylam for hypercholesterolemia (Leqvio, developed and commercialized by Novartis), acute hepatic porphyria (Givlaari) and primary hyperoxaluria type 1 (Oxlumo). Apart from Alnylam and its partners Sanofi and Novartis, the only other company to get an siRNA drug onto the market so far is Novo Nordisk, whose Rivfloza (nedosiran), approved by the FDA in 2023, treats the rare genetic disease primary hyperoxaluria type 1 (PH1). Testing the Limits So far, all of these therapies have targeted processes in the liver—including Amvuttra, which takes aim at cardiac outcomes via knocking down transthyretin (TTR) in hepatic cells. But experts who spoke with BioSpace said that could soon change. “Where we’re starting to see innovation—and it still is early stage, although it looks very promising—is trying to deliver to new tissues,” Minter said. That targeting problem is “the major question in the field that we’re working on right now.” Andrew Adams, Eli Lilly’s group vice president, molecule discovery and director of the Lilly Institute for Genetic Medicines, echoed this. GalNAc has thus far been a “unicorn” in the field in terms of its specific and safe delivery, and “we have a lot of work to do to open up si[RNA]beyond the hepatocyte, but . . . probably once we crack it is going to be similar to when Alnylam and others initially cracked GalNAc, and you’ll just sort of walk your way down the list of indications in the new tissue that you open up,” he told BioSpace . “I think probably the most interesting space for the field right now is in delivery to the brain and going after diseases of the brain,” he said, citing Alnylam’s candidate mivelsiran, currently in Phase II for cerebral amyloid angiopathy and Phase I for Alzheimer’s disease. Lilly, too, is pursuing neurodegenerative targets with siRNA, Adams added. Other tissues with promising early data include adipose and lung. In a March conference presentation, for example, Arrowhead Pharmaceuticals released mouse data on two siRNA candidates devised to reduce body fat while preserving lean muscle mass. One targets hepatic cells’ expression of a gene, INHBE , that is involved in metabolic processes, while the other silences expression of ALK7 , a gene needed for fat storage, in lipocytes. Early clinical studies on both candidates have begun. And last spring, Arrowhead announced interim results of a Phase I/II study of ARO-RAGE, an siRNA that targets lung tissue and silences the receptor for advanced glycation end-products, a mediator of type 2 inflammation. In study participants with asthma, two doses of the candidate reduced serum levels of the target protein by up to 88%, the company reported. siRNA’s limitations don’t end at targeting. It can’t be used to completely knock out expression of a gene, only knock it down, and it can’t by itself be used against multiple genetic targets, Jadhav noted. In addition, RNAi can only dial gene expression down, so it can’t be used to directly boost levels of a deficient protein. Researchers have found workarounds for this in some cases, though. Jadhav cited the example of Givlaari, which treats acute hepatic porphyria. “In this metabolic pathway, the heme biosynthesis, one of the enzymes is mutated, and because of that, you have toxic intermediates that build up,” he said. Since siRNA can’t replace the mutated enzyme, the therapy instead targets a different enzyme, GO, that’s upstream of the toxic intermediates, lowering their levels. siRNA’s successes could pave the way for a more permanent treatment option, Adams said. “Once you’ve generated enough evidence over a long enough period of time in enough patients that getting rid of this protein [via siRNA] has no negative consequences in an adult . . . Probably at that point you start to feel confident to permanently change something, but I think the bar should be and is high for things that people will tolerate permanent genetic changes for,” he said. He raised the example of Leqvio, which targets the enzyme PCSK9 in order to lower cholesterol levels. Verve Therapeutics now has a gene editor targeting the same enzyme in early clinical trials. Jadhav allowed that gene editing could become a competitor to siRNA in some cases. “I think at the end of the day, any solution . . . biopharma brings for the patients would be great,” he said. “At the same time, we feel that with RNAi, we can achieve [a] durable level of activity and still be reversible. You kind of get the best of both things. So we remain very confident and very optimistic about the future of RNAi.” Looking ahead, Minter summarized what he sees as the prospects for siRNA: “we’re at the precipice where we’re waiting, but it’s an exciting five to ten years ahead for the field, no doubt.”

关注并星标CPHI制药在线RNA疗法正迅速成为现代医学中最具变革性的治疗策略之一。从反义寡核苷酸（ASO）和小干扰RNA（siRNA）等精准调控基因表达的工具，到mRNA疫苗和肿瘤免疫疗法等前沿应用，RNA技术已在多个疾病领域展现出巨大潜力。近年来，随着递送系统、生物偶联技术和修饰化学的不断进步，RNA疗法的临床管线迅速扩展，涵盖了罕见病、神经系统疾病、代谢性疾病以及肿瘤等多个领域。目前，RNA疗法的临床开发全景涵盖了ASO、siRNA、mRNA、核酸适体（aptamer）等主要技术路径，在不同适应症中布局广泛，关键企业的研发动态频繁，已获批上市的代表性药物不断涌现。本文总结了现有管线和上市的 RNA疗法，将这一新兴领域的开发全景呈现出来。1. ASO类 RNA资产梳理      1.1 I期ASO资产      • Praxis       ASO资产 ：Elsunersen（PRAX-222）       靶点：SCN2A基因       适应症：由SCN2A基因的功能获得性突变引起的早发性SCN2A发育性和癫痫性脑病。      • PYC Therapeutics       ASO资产：VP-001       靶点：PRPF31基因       适应症：由PRPF31基因突变引起的视网膜色素变性11型       ASO资产：PYC-001       靶点：OPA1基因       适应症：由OPA1基因突变引起的常染色体显性视神经萎缩（ADOA）       ASO资产：PYC-003       靶点：PKD1基因       适应症：常染色体显性多囊肾病（ADPKD）      • Bio-Path Holdings       ASO资产：BP1002（Liposomal Grb2 ASO）       适应症：急性髓性白血病（AML）、B细胞淋巴瘤（B-cell lymphoma）       技术特点：使用独特的中性脂质体递送系统（DNAbilize® Platform）递送ASO。1.2 II期ASO资产      • Stoke Therapeutics       ASO资产：Zorevunersen（STK-001）       靶点 ：SCN1A基因       适应症：Dravet综合征（一种严重癫痫）       ASO资产 ：STK-002       靶点：OPA1基因       适应症：常染色体显性视神经萎缩（ADOA）      • Entrada Therapeutics       ASO资产：ENTR-601-44       适应症：Duchenne肌营养不良（DMD）       靶点 ：DMD中的Exon 44跳跃     技术特点：使用Entrada独有的分子穿透技术（Endosomal Escape Vehicle, EEV）提高细胞内递送效率。       ASO资产：ENTR-601-45       靶点：DMD基因的外显子45（Exon 45）       适应症：适用于外显子45跳跃的杜氏肌营养不良症（DMD）患者      • Dyne Therapeutics       ASO资产：DYNE-251      适应症：Duchenne肌营养不良（DMD），针对DMD中的Exon 51跳跃。       技术特点：使用抗体-寡核苷酸结合平台（FORCE platform）进行肌肉组织特异性递送。       ASO资产 ：DYNE-101       适应症：肌强直性营养不良症1型（DM1）       靶点：DMPK基因的异常CTG重复序列      • Ribomic      ASO资产：Umedaptanib Pegol（原RBM-007，严格来说是核酸适体aptamer，而不是典型ASO)       靶点 ：FGF2（成纤维细胞生长因子2）。       适应症：湿性年龄相关性黄斑变性（wAMD），软骨发育不全症       • Wave Life Sciences       ASO资产：       WVE-N531：DMD（杜氏肌营养不良症）治疗，靶向Exon 53跳跃       WVE-003：亨廷顿舞蹈症（Huntington's Disease, HD），靶向HTT基因突变      • PepGen       ASO资产：PGN-EDO51       适应症：Duchenne肌营养不良（DMD）   技术特点：结合增强型细胞穿透肽（Enhanced Delivery Oligonucleotide, EDO）技术，提高ASO进入肌肉细胞的效率。       ASO资产 ：PGN-EDODM1       靶点：DMPK基因的异常CUG重复序列       适应症：肌强直性营养不良症1型（DM1）      • 罗氏       ASO资产 ：Tominersen（RG6042）       靶点：Huntingtin（HTT）基因       适应症：亨廷顿病（Huntington's Disease, HD）       ASO资产 ：IONIS-FB-LRx（RO7434656 / RG6299）       靶点：补体因子B（Factor B）       适应症：IgA肾病（IgAN）      • Ultragenyx       ASO资产 ：GTX-102       靶点：UBE3A-AS（UBE3A反义转录本）       适应症：天使综合征（Angelman Syndrome）1.3 ASO类3期资产      • Oncotelic Therapeutics       ASO资产：OT-101（也叫Trabedersen）       靶点：转化生长因子β2（TGF-β2）       适应症：胶质母细胞瘤（GBM）、胰腺癌、恶性黑色素瘤       机制：抑制TGF-β2，有望减轻肿瘤免疫抑制，增强抗肿瘤免疫反应      • 阿斯利康       ASO资产：ION449（亦称AZD8233），与Ionis合作开发的ASO疗法       靶点：PCSK9（一种影响低密度脂蛋白胆固醇LDL-C水平的蛋白质）       适应症：高胆固醇血症（hypercholesterolemia）      备注：主要竞争对手包括小分子抑制剂和PCSK9单抗（如Repatha、Praluent）      • GSK       ASO资产：bepirovirsen       靶点：乙型肝炎病毒（HBV）的前基因组RNA和mRNA       适应症：慢性乙型肝炎（chronic hepatitis B, CHB），通过抑制HBV基因表达，帮助病毒清除或实现功能性治愈（functional cure）。      • 诺华       ASO资产：Pelacarsen       靶点：LPA基因（编码脂蛋白(a)）       作用机制：Pelacarsen通过抑制LPA基因的mRNA，降低血液中脂蛋白(a)(Lp(a))水平，从而降低心血管疾病风险。Lp(a)是目前被认为的重要但尚无针对性治疗手段的心血管风险因子。       适应症：主要用于治疗动脉粥样硬化性心血管疾病高危患者中，血脂异常（特别是Lp(a)升高）的情况。       临床阶段：正在进行III期临床试验（Lp(a)HORIZON）。Pelacarsen可能成为首个专门针对Lp(a)升高治疗获批的药物。1.4 ASO类上市药物      • 渤健       Spinraza（nusinersen）       靶点：SMN2前体mRNA（促进功能性SMN蛋白表达）       适应症：脊髓性肌萎缩症（SMA）       获批时间：2016年12月（美国FDA批准）      备注：全球首个获批的SMA治疗药物。由Ionis开发，Biogen负责商业化。      • Sarepta Therapeutics       Exondys 51（eteplirsen）       靶点：DMD基因的Exon 51       适应症：Duchenne肌营养不良（DMD）       获批时间：2016年9月（FDA加速批准）       Vyondys 53（golodirsen）       靶点：DMD基因的Exon 53       适应症：DMD       获批时间：2019年12月       Amondys 45（casimersen）       靶点：DMD基因的Exon 45       适应症：DMD       获批时间：2021年2月（FDA加速批准）      • Ionis Pharmaceuticals       Tegsedi（inotersen）       靶点：TTR（转甲状腺素蛋白）       适应症：遗传性转甲状腺素蛋白淀粉样变性多发性神经病（hATTR-PN）       获批时间 ：2018年10月（FDA，EMA批准）      Waylivra（volanesorsen）       靶点：APOC3（载脂蛋白C-III）       适应症：家族性乳糜微粒血症综合征（FCS）       获批时间：2019年5月（欧洲EMA批准；未获美国FDA批准）      • NS Pharma       Viltepso（viltolarsen）       靶点：DMD基因的Exon 53       适应症：Duchenne肌营养不良（DMD）       获批时间：2020年8月（FDA加速批准）2.RNAi类 RNA资产2.1 I期RNAi资产      • Aligos Therapeutics       RNAi资产：ALG-125755       靶点：乙型肝炎病毒（HBV）RNA       适应症：慢性乙型肝炎（CHB）      • Regulus Therapeutics       RNAi资产：RGLS8429       靶点：microRNA-17（miR-17家族）       适应症：常染色体显性多囊肾病（ADPKD）      • Phio Pharmaceuticals       RNAi资产：PH-762       靶点：程序性死亡受体1（PD-1）       适应症：癌症免疫疗法（通过下调T细胞表面PD-1，增强免疫杀伤）       技术特点：采用其自有的INTASYL✓平台，优化了siRNA的稳定性和局部递送。      • TransCode Therapeutics       RNAi资产：VIR-2218 TTX-MC138       靶点：microRNA-10b（miR-10b）       适应症：针对转移性实体肿瘤（如乳腺癌、胰腺癌、脑肿瘤等）       技术特点：使用纳米颗粒系统高效递送siRNA药物，特别适合针对深部转移灶。2.2 II期RNAi资产      • Arbutus Biopharma       RNAi资产：AB-729       靶点：乙型肝炎病毒（HBV）表面抗原（HBsAg）       适应症：慢性乙型肝炎（CHB）       备注：AB-729是Arbutus当前最重要的核心资产之一。      • OliX Pharmaceuticals       RNAi资产：OLX703A       靶点：HBV病毒相关RNA       适应症：慢性乙型肝炎（CHB）       机制：抑制HBV病毒蛋白表达      • Silence Therapeutics       RNAi资产：SLN360       靶点：LPA基因（编码脂蛋白Lp(a)）       适应症：高脂蛋白(a)血症（Lp(a)过高相关的心血管疾病）       机制：通过降低血液中Lp(a)水平，减少动脉粥样硬化风险。       备注：SLN360是Silence在心血管RNA疗法领域的主力项目。      • Sirnaomics       RNAi资产：STP705       靶点：双靶点siRNA药物，靶向TGF-β1和COX-2。       适应症：瘢痕治疗（皮肤纤维化）、非黑色素瘤皮肤癌（如基底细胞癌、鳞状细胞癌）       机制：抑制纤维化、降低肿瘤微环境免疫抑制。       备注：Sirnaomics的特点是双靶点siRNA联合递送。      • GSK       RNAi资产：GSK4532990       靶点：靶向HSD17B13基因       适应症：代谢功能障碍相关脂肪性肝炎（MASH）      • 礼来       RNAi项目：LY3561774       靶点：SERPINA1基因       适应症：α1-抗胰蛋白酶缺乏症（AATD）       机制 ：降低异常α1-抗胰蛋白酶（AAT）积聚      • VIR Biotechnology       RNAi项目：VIR-2218       靶点 ： HBV RNA       适应症：慢性乙型肝炎（CHB）。       机制：抑制HBV表面抗原表达      • 罗氏       RNAi资产：Zilebesiran       靶点 ：肝脏表达的血管紧张素原（AGT）基因。       适应症：高血压，特别是高心血管风险患者。2.3 III期RNAi资产      • Arrowhead Pharmaceuticals       RNAi资产：ARO-APOC3       靶点 ：APOC3（载脂蛋白C-III），       适应症：高甘油三酯血症和罕见脂代谢异常      • 武田       RNAi资产：Fazirsiran       靶点：SERPINA1（编码α1-抗胰蛋白酶）       适应症：α1-抗胰蛋白酶缺乏症（AATD）引起的肝病      • 安进       RNAi资产：Olpasiran       靶点：LPA基因（脂蛋白(a)）       适应症：高脂蛋白(a)血症及其引发的心血管疾病风险       备注：这是一款非常重磅的RNAi项目，对心血管领域意义重大。      • Avidity Biosciences       RNAi资产：AOC 1001       靶点：DMPK基因（导致肌强直性营养不良症1型DM1）       适应症：肌强直性营养不良症1型（DM1）       技术特点：AOC（Antibody Oligonucleotide Conjugate，抗体-寡核苷酸偶联体），用于肌肉靶向递送siRNA。      • 赛诺菲       RNAi资产：Fitusiran       靶点：AT（抗凝血酶）       适应症：血友病A或B患者的出血预防      • VIR Biotechnology       RNAi资产：VIR-2218       靶点：HBV RNA       适应症：慢性乙型肝炎（CHB）2.4 上市RNAi资产      • Alnylam Pharmaceuticals       Alnylam是全球RNAi疗法先锋，拥有最多已上市RNAi药物。       Onpattro（Patisiran）       靶点：TTR      适应症：遗传性转甲状腺素蛋白淀粉样变性引起的多发性神经病（hATTR-PN）       批准情况：2018年FDA/EMA批准       Givlaari（Givosiran）       靶点：ALAS1       适应症：急性肝卟啉症（AHP）       批准情况：2019年FDA/EMA批准       Oxlumo（Lumasiran）       靶点：HAO1       适应症：原发性高草酸尿症1型（PH1）       批准情况：2020年FDA/EMA批准       Amvuttra（Vutrisiran）       靶点：TTR      适应症：遗传性转甲状腺素蛋白淀粉样变性引起的多发性神经病（hATTR-PN）（长效皮下注射版）       批准情况：2022年FDA批准      • 诺华       RNAi资产：Leqvio（Inclisiran）       靶点：PCSK9       适应症：高胆固醇血症，动脉粥样硬化性心血管疾病风险降低       批准情况：2020年欧洲EMA批准；2021年底美国FDA批准      • 诺和诺德       RNAi资产：Rivfloza (nedosiran)       靶点：肝脏中乳酸脱氢酶（LDH）mRNA     适应症：治疗9岁及以上、肾功能相对良好的原发性高草酸尿症1型（PH1）患者。       作用机制：抑制LDH蛋白表达，减少草酸过度生成，缓解PH1疾病过程，减少肾脏损害风险。       批准情况：2023年9月29日FDA正式批准Rivfloza上市。成为继Alnylam的Oxlumo（Lumasiran）之后，全球第二款获批用于PH1治疗的RNAi药物。3.mRNA类 RNA药物资产3.1 1期mRNA资产      • 赛诺菲       SP0237: 季节性流感 mRNA 疫苗       适应症：针对 A/H3N2 毒株的季节性流感。       SP0256 – RSV mRNA 疫苗（老年人群）       适应症：用于预防老年人群中的呼吸道合胞病毒（RSV）感染。       SP0268 – mRNA 痤疮疫苗       适应症：针对痤疮（Acne）的 mRNA 疫苗。       SP0291 – 多价呼吸道病毒 mRNA 疫苗      适应症：针对 RSV、人类偏肺病毒（hMPV）和副流感病毒 3 型（PIV3）的组合疫苗，主要用于老年人群。       沙眼衣原体（Chlamydia）mRNA 疫苗候选       适应症：预防沙眼衣原体感染，主要针对 18 至 29 岁的成人。      • Vertex       mRNA资产：VX-522：用于囊性纤维化（CF）的mRNA疗法       靶点：CFTR基因（囊性纤维化跨膜电导调节因子）。       适应症：无法通过CFTR调节剂治疗的CF（囊性纤维化）患者，尤其是那些由于CFTR基因突变导致CFTR蛋白缺失的患者。       作用机制：VX-522是一种mRNA疗法，通过脂质纳米颗粒（LNP）递送CFTR mRNA至肺部细胞，促使其合成功能性CFTR蛋白，从而恢复氯离子通道的功能。3.2 II期mRNA资产      • Gritstone Bio       GRANITE（GRT-C901/GRT-R902）      个体化肿瘤新抗原疫苗，采用腺病毒（ChAd68）和自扩增mRNA（samRNA）组成的异源prime-boost策略。       适应症：用于治疗转移性微卫星稳定型结直肠癌（MSS-CRC）。       CORAL       基于自扩增mRNA（samRNA）的COVID-19疫苗，诱导广泛且持久的中和抗体和T细胞免疫反应。      • CureVac/GSK       季节性流感mRNA疫苗候选       该疫苗候选基于CureVac的第二代mRNA平台，针对流感病毒株，包括A型和B型毒株。       COVID-19 mRNA疫苗候选CV0601和CV0701       CV0601为单价疫苗，编码Omicron BA.4/5变异株的刺突蛋白；CV0701为二价疫苗，编码Omicron BA.4/5变异株和原始SARS-CoV-2毒株的刺突蛋白。3.3 III期mRNA资产      • 第一三共       DS-5670a（原始毒株单价疫苗）       适应症：Covid-19疫苗，作为加强针用于已完成初始疫苗接种的成人和老年人。       DS-5670a/b（原始毒株与Omicron BA.4/5二价疫苗）       适应症：Covid-19疫苗，作为加强针用于12岁及以上已完成初始疫苗接种的人群。       DS-5670d（Omicron XBB.1.5单价疫苗）       适应症：Covid-19疫苗，作为季节性加强针用于12岁及以上人群，包括未接种疫苗者。      • 默沙东       mRNA资产：V940（mRNA-4157）       类型：肿瘤疫苗（个体化mRNA疫苗）       适应症：手术切除后的高风险黑色素瘤患者辅助治疗       靶点：个体化新抗原（根据患者肿瘤突变特异设计）3.4上市mRNA资产      • Arcturus Therapeutics       mRNA资产：KOSTAIVE（ARCT-154 / Zapomeran）       类型：自扩增mRNA（sa-mRNA）疫苗       适应症：用于预防COVID-19，适用于18岁及以上人群       靶点：SARS-CoV-2病毒刺突蛋白（Spike protein）      • BioNTech/辉瑞       Comirnaty       类型：mRNA疫苗       适应症：用于预防COVID-19，适用于6个月及以上人群       靶点：SARS-CoV-2病毒刺突蛋白（Spike protein）       获批时间：✓2020年12月获得FDA紧急使用授权，2021年8月获得美国FDA完全批准      • 莫德纳       Spikevax       类型：mRNA疫苗       适应症：用于预防COVID-19，适用于6个月及以上人群       靶点：SARS-CoV-2病毒刺突蛋白（Spike protein）       获批时间：2020年12月18日，美国FDA授予紧急使用授权；2022年1月31日，获得FDA完全批准Ref.       TD Cowen.       Pharmaceuticals’ websitesEND【企业推荐】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~