Nonetheless, many non-profit groups see promise in supporting trials into drug repurposing. Epidemiological data can offer enticing leads. An insurance database in Taiwan shows a 76% reduction in the risk of tuberculosis among diabetic patients on metformin, and progressively larger protective effects with higher cumulative doses. However, Udai Banerji, a researcher at the Institute of Cancer Research in London, warns that randomised clinical trials are necessary to prove definitively the value of a drug to treat a new disease.
许多非营利组织反而支持涉及“老药新用”的一系列临床试验。流行病学数据在这方面起到很好的带头作用。台湾的一家保险数据库显示，使用二甲双胍的糖尿病患者在结核病患病风险上降低了76%左右，并且逐步增加的二甲双胍用量对病人起的保护效果也会更加显著。Udai Banerji，一位伦敦癌症研究中心的研究员并不这么认为。他表示想要确切证明这些药物可以治疗新的疾病必须进行严格的临床试验。
Trials are costly, but the benefits can be huge. The Drugs for Neglected Diseases Initiative, a Swiss non-profit research group, supported r&d into fexinidazole, which was abandoned by a pharma firm at an early stage but was then found to show anti- -parasitic qualities. This January, after years of work, it was approved for sleeping sickness in the Democratic Republic of Congo. It is the first oral medicine for the disease, and works for all stages of it.
临床试验虽然造价昂贵，但好处也是不言自明。“忽略病用药组织”是瑞士一家非营利科研机构，他们展开了对非昔硝唑的科研计划，曾有一家药企对该药展开过初期研究，但很就快放弃了，后来该药被证明具有抗寄生虫的效果。今年一月，经过多年努力，刚果民主共和国批准了该药品的上市，主要针对昏睡病患者。这是第一款用于昏睡病的口服药，并且适用于所有病程。
When it comes to cancer, some of the most promising generic pills are already well-known. Cancer Research uk, a charity, is testing aspirin to see if it can stop cancer recurring; metformin in a large prostate- cancer trial; and an anti-fungal medication to treat bowel cancer. The Anticancer Fund in Brussels has high hopes for propranolol in treating angiosarcoma—cancers of the inner lining of blood vessels—and for pancreatic cancer. Propranolol is a generic 1960s beta-blocker used for a wide range of ailments such as hypertension, anxiety and migraine. If approved for cancer, its price would be negligible compared with the tens of thousands of dollars a month normally charged for cancer medicines. Mr Banerji estimates that one cancer drug in five that goes off-patent is likely to have uses in treating other cancers. It is “almost free money”, he says.
许多常规药在癌症治疗方面已经非常有名了。英国癌症研究是一家公益性组织，他们测试了阿斯匹林在抗癌复发方面的效果，开展了二甲双胍针对前列腺癌的大型临床试验，以及抗真菌药物对肠癌的治疗效果试验。位于布鲁塞尔的抗癌基金会对普萘洛尔在治疗恶性血管皮内细胞瘤和胰腺癌方面寄予厚望，普萘洛尔是一种β-受体阻滞药，在上世纪60年代是一种治疗高血压，焦虑症和偏头痛的常规药物。如果该药被批准用于癌症治疗，癌症病人的用药负担就会小很多了。Banerji先生预测到，约两成用于癌症治疗的非专利期药物将可用于更多种类癌症的治疗。“这相当于免费了。”
The Anticancer Fund believes that the path to wider uptake of repurposed drugs is through approval and relabelling by drug regulators for new treatments. Although difficult and expensive, Mr Pantziarka says it unleashes a cascade of important events. When a regulator licenses a drug, clinical guidelines are updated, drug formularies are changed, reimbursement should follow more smoothly and clinicians gain experience using it. In America Mr Bloom agrees that relabelling will encourage the usage of repurposed drugs.
这家抗癌基金会认为，新用途药品想要获得更广泛的接受程度往往需要药品监管部门的许可以及更换旧的药品标签。此举尽管难以实现并且造价高昂，Pantziarka 先生表示，这会推动一系列重要事件被提上日程。当监管机构批准了一种药品的应用，相关的临床用药指南就需要更新，处方集就需要改变，报销政策就得跟上步伐，临床医生就得积累相应的用药经验。Bloom先生也同意更换药品标签对推动“老药新用”有一定促进作用。
Money, though, is a crucial constraint. Even governments keen to pump cash into drug development prioritise drugs with patents. Mr Pantziarka says many official funding schemes, such as the eu’s Horizon2020 programme, want projects that hold
intellectual property. In America the National Centre for Advancing Translational Sciences will support research to help drug companies repurpose molecules for which they hold patents.
钱往往是一个很关键的制约因素。尽管政府十分希望将资金投入到药品开发的项目中，但很多官方资助计划（如欧盟的视野2020计划）往往需要开发项目组具有知识产权。在美国，全国转化科学推进中心（NCATS）将资助那些帮助药企获得专利权的研究项目，这些项目常常帮助药企重构药品的分子组成。
Finance is not the only obstacle. Only the makers or original developers of a drug are permitted to adjust its label. Sanofi, based in Paris, was the firm that requested regulatory review of fexinidazole for sleeping sickness—although the r&d was a charitable effort. But drug firms are not obliged to support non-commercial efforts to repurpose drugs. And outside the industry it is hard to find the legal expertise to manage the necessary paperwork.
融资并不是唯一的障碍。如果一家制药机构想要调整某个药品的标签，那么他们就必须获得该药品原始开发者的许可。赛诺菲，一家位于巴黎的药企，他们要求用于昏睡病的非昔硝唑开发需要提供监管部门出示的审查报告。尽管对于该药品新用途的科研投入完全是出于公益考虑，但药企们也没有义务向新用途药提供商业以外的任何支持。并且，在制药领域以外也很难找到具有法律资质的机构提供必要的文书服务。
Some of these concerns are under review by an expert group on repurposing within the European Commission. It is looking at how regulatory changes, as well as legal and financial support, could support repurposing by third parties such as charities and foundations. The Anticancer Fund wants the regulator to be able to evaluate evidence on drugs that has been submitted by third parties such as itself.
在欧洲委员会内部，这些问题也得到了相关专家团体的重视。专家们的关注点主要集中在管控政策调整以及财政支持这两个方面，在第三方机构的（如公益组织或基金会）监管实施下，新用途药的开发会得到一定程度重视。抗癌基金会希望监管部门能够评估他们呈递的药物新用途相关的实证证据，这家基金会就是一个合格的第三方机构。
As non-profits make headway in repurposing, corporate interest may be rising. Mr Bloom says that ten years ago not a single pharma company would have anything to do with his charity. Today he receives calls from at least two or three small- to mid-sized firms every month saying they are interested. In terms of achieving new treatment options, this is good news. But it will not bring cheaper medicines in areas traditionally neglected by the drug industry. Firms will focus on finding ways to patent the new uses—through reformulation or new combinations of substances—and charge high prices for the finished product.
非营利组织在扩展药物用途方面不断取得进展，相关企业也抱有了更大的兴趣。Bloom先生表示，10年以前，还没有任何一家药企和他组织的公益项目有什么联系，如今，他每个月可以收到来自两三家中小型企业发来的致电咨询，表示他们对这些项目很感兴趣。从为病人提供更多治疗选择的角度看，这是一件好事，但此举并不会降低药物的价格，尤其是长期被制药工业忽略的药品领域。药企会不断寻求机会为其新用途药申请专利，常见的途径包括，药品分子重构或加入新的物质，如此药企就可以向成品收取更加高额的费用。
If governments want cheaper drugs, non-profits will need financial incentives and a helpful regulatory framework. Would-be repurposers have come up with some suggestions. They include making regulators give free advice and waive approval fees, and a public fund to support re- purposing. Another idea is a “social-impact bond”—backed by private investors funding a range of drug trials for diseases that cost public-health services a lot of money to treat. When drugs are approved, investors are paid back by the public health service, which makes savings by using the newly approved generic drugs.
如果政府要求药品的价格下调，那么非营利机构就需要一定的财政补贴和适应的监管框架。潜在的新用途药生产商已经提出了一些建议，包括要求监管机构提供免费的咨询服务，免除审查费用，以及建立相应的公共基金。另一种想法是构建“社会影响链”，在私人投资者的财政支持下，向那些曾花费大量公共医疗服务资源的疾病药品试验提供资金支持。当这些药品获批上市时，投资者会通过公共医疗服务的途径获得回报，因为相关医疗机构需要按规定使用这种新用途药。
Patiently waiting
耐心等待
The slow pace of change leaves patients like Alistair stranded. Care Oncology says it will publish results from its glioblastoma patients this spring. Though welcome, this will fall short of the gold-standard trial evidence needed to register a drug. The treatment will be left in limbo. And patients will be left to wonder why governments fail to see the purpose of repurposing drugs.
改变的发生总是缓慢的，像阿里斯塔尔这样的患者不得不再等等。肿瘤护理诊所表示，有关胶质母细胞瘤患者的用药调查结果将在今年春天发布。患者们虽然很欢迎这样的疗法，但它们还是和相关金标准试验证据有很大的差距，因此难以获批成为新用途药。这样的疗法可能被搁置起来，留给患者们的也只有疑惑，为什么政府还是看不到新用途药的价值呢？
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