2014年10月14日讯 /生物谷BIOON/ --抗体药物偶联物（Antibody Drug Conjugates，ADC）是一类新颖的治疗药物，正日益受到全球制药公司的关注。ADC药物由单克隆抗体和强效毒性药物（toxic drug）通过生物活性连接器（linker）偶联而成，是一种定点靶向癌细胞的强效抗癌药物。由于其对靶点的准确识别性及非癌细胞不受影响性，极大地提高了药效并减少了毒副作用。
近几年，全球已掀起抗体药物偶联物（ADC）研发的热潮。ADC类药物被认为能够更加高效和有效的治疗疾病，在未来将成为治疗疾病的重要手段。
根据全球知名市场调研公司Research & Markets发布的一份新报告，未来10年，ADC市场将经历飞速发展。目前，由于仅有2个ADC药物（Adcetris，Kadcyla）上市，2014年ADC市场市值预计将超过6亿美元。未来10年，预计将有7-10个ADC新药上市，2024年ADC市场将达到100亿美元。
根据报告内容，当前，ADC市场仍处于起步阶段，仅有2个药物上市，即武田和西雅图遗传学公司的Adcetris和罗氏的Kadcyla。不过，已有数个ADC药物处于临床开发阶段，其中大部分开发用于肿瘤适应症。制药公司非常热衷于将创新的药物分子添加至药物管线，而极具新颖性的ADC药物，提供了一个绝佳的机会。
尽管目前ADC市场中已有几个大型制药公司，但ADC开发的技术能力仍依赖于少数几个技术提供商。西雅图遗传学公司（Seattle Genetics）和ImmunoGen是ADC领域的先驱，大部分在研ADC药物采用了它们的技术，主要是通过技术授权协议获得。在未来，该领域中预计将会达成更多的联合开发协议。
随着数个ADC药物的预期上市，ADC市场中的投资预计将进一步增加。药物开发商/风险投资商正在生物制剂领域投入大量资金，但投向ADC研发的比例仍有待观察。随着制药巨头寻求获得ADC市场的竞争优势，当前的市场格局将进一步演变。ADC市场未来增长机会十分可喜，但同时也存在着一些挑战。
——目前，仅有2个ADC药物（Adcetris，Kadcyla）上市，随着销售的预期增长，2014年ADC市场市值预计将超过6亿美元。未来10年，预计将有7-10个ADC新药上市，2024年ADC市场将达到100亿美元。
——目前，约有45个ADC药物处于临床开发。其中，约25%处于II期/III期阶段，而临床前管线正在迅速扩张。
——在研ADC药物中，最常用到的细胞毒制剂包括阿里他汀（auristatin）、卡奇霉素（calicheamicin）、美登素（maytansine）和倍癌霉素（duocarmycin）。其中，阿里他汀占主导地位，约占在研ADC药物的50%以上。
——罗氏有10个在研ADC新药，拥有最发达的ADC管线。在技术和创新方面，其他新近进入ADC市场的制药公司包括牛津生物治疗公司（Oxford BioTherapeutics）、Mersana Therapeutics、Abzena，这些公司提供的新颖技术，将帮助推动ADC市场的发展。
——西雅图遗传学公司（Seattle Genetics）和ImmunoGen公司是最活跃的2家公司，为大量在研ADC药物提供了专利性的ADC技术。
——目前，有70%-80%的ADC生产为外包（outsourced）。有能力开发连接器和细胞毒素的合同生产商数目非常有限，能够提供ADC药物共轭服务的合同生产商更为有限。
——过去几年中，已经开发了一些ADC技术。然而，更稳定的连接器和更强效的细胞毒素，将确保新一代ADC药物具有改善的安全性和疗效。
英文原文：Antibody Drug Conjugates Market (2nd Edition), 2014 - 2024
Antibody drug conjugates (ADCs) are a new class of therapeutic agents, gaining increasing attention from both large and small pharmaceutical companies. Generally
addressed as the marriage of an antibody with a toxic drug / chemotherapy drug, these conjugates are believed to be more efficient and effective in the treatment of a
disease.
The ADC market is still in its infancy. At present, Adcetris and Kadcyla are the only two marketed drugs. However, there are several ADCs under development, with most
of them being developed for oncological indication. Pharmaceutical companies are keen to add innovative molecules to their diminishing product pipelines and ADCs
provide an attractive opportunity due to their novel nature.
Although the market now has presence of several large pharmaceutical companies, the technological capabilities for development of ADC still lies with a few technology
providers. Seattle Genetics and ImmunoGen are amongst the pioneers in the field of ADC, with most pipeline ADCs using their technology. Most development to date has
been carried under technology license agreements. However, we expect to see more co-development agreements in the future.
As more ADCs move from pipeline to the market, there is likely to be a further increase in investments in this area. Drug developers / venture capital firms are
investing huge amount of money in biologics and it remains to be seen what proportion of this will be directed towards ADCs. The current market landscape will
gradually evolve as large pharmaceutical companies look to gain competitive advantage in the ADC market. The future of the market is promising, though there are
several challenges to meet.
- Driven by the sales of Adcetris and Kadcyla (the two drugs currently available commercially), the ADC market is likely to be worth more than USD 600 million in 2014.
- About 45 molecules are currently in clinical development. Of these, approximately 25% are in Phase II or Phase III of development. As expected, the preclinical
pipeline is also gradually expanding.
- Most commonly used cytotoxins for ADCs under clinical development include auristatin, calicheamicin, maytansine and duocarmycin. Auristatin dominates the market and
accounts for over 50% of ADCs in clinical development.
-Roche, with 10 molecules in clinical development, has the most developed pipeline of ADCs. Relatively new entrants such as Oxford BioTherapeutics, Mersana
Therapeutics, Abzena are likely to provide the necessary push (both in terms of technology and innovation).
- Seattle Genetics and ImmunoGen are the two most active companies offering their proprietary ADC technologies to a large number of ADCs under development.
- About 70%-80% of ADC manufacturing is currently outsourced. There are limited number of contract manufacturers with capabilities for development of linkers and
cytotoxins. In addition, even fewer CMOs provide conjugation services for ADC.
- Several technological developments have taken place in the recent past; more stable linkers and potent cytotoxins are likely to ensure that the next generation ADCs
have improved safety/efficacy profile.
- With around 7-10 new ADC commercial launches over the coming decade, we believe the overall market will be worth USD 10 billion annually by 2024.