美国孤儿药开发的政策、策略与实践

简述了罕见病及孤儿药的定义和研发意义,重点介绍了美国针对孤儿药开发的现有制度法规、激励政策及管理经验,并以实例 分析从研发、注册和上市等角度探讨了美国孤儿药开发的策略,旨在为从事孤儿药开发工作的人士提供参考。     

“首届中国孤儿药研发论坛”专家观点

对2015 年4 月25 日召开的“首届中国孤儿药研发论坛”的专家报告内容进行归纳总结,旨在为从事罕见病诊断和孤儿药研发工 作的人士提供信息参考。报告内容涉及国内外孤儿药研发现状和前景、中国孤儿药政策和审评状况、罕见病诊断以及中国孤儿药研发的机 会等。     

罕见病治疗用药的发展态势分析

<正>长期以来,罕见病的治疗用药(孤儿药)的开发并未受到重视,因此21世纪以来各国通过罕见病治疗用药物相关法规的建立,来刺激孤儿药的开发。与此同时,在普通疾病的用药开发陷入困难之际,世界各大制药企业也将目光投向了孤儿药的研发。文章就孤儿药的开发现状和部分孤儿药的市场前景进行了分析。     

我国亟需推动罕见病用药的研发和产业化

<正>罕见病一般指患病人数不足总人口1‰的疾病,全球已知的罕见病约有7 000种。用于罕见病治疗的"孤儿药"已经成为全球医药产业的重要分支,预计到2020年将占到全球处方药销售额的19.1%。我国罕见病诊疗和孤儿药研发尚处于起步阶段,推动相关研究具有重要的社会、经济意义和学术价值。首先,我国罕见病患者的绝对数量多,利用质优价廉的自主药品代替价格昂贵的进口产品,可大幅降低患者负担,并创造巨大     

罕见病基因治疗与孤儿药

孤儿药因面向的罕见病患者群小、市场需求低、研发成本高、缺乏政策支持等,其发展面临困境。随着精准医疗概念的提出,基 因治疗因能够从根本出发,给患者提供 “一劳永逸”的治疗,备受关注。基因治疗以单基因罕见病的治疗作为极佳切入点,为孤儿药的 研发带来了新的希望。概述基因治疗针对的疾病对象、实施策略和属性以及基因药物的结构及基因治疗的载体,以血友病的基因治疗为 例回顾罕见病基因治疗的发展,并分析罕见病基因治疗药物研发现状。     

“首届中国孤儿药研发论坛”专家观点（续）

对 2015 年 4 月 25 日召开的“首届中国孤儿药研发论坛”与会专家对话内容进行归纳总结,旨在为从事罕见病诊断和孤儿药研发工作的人士提供信息参考。来自产、学、研领域的专家从研发、临床、审评、投资、媒体等角度探讨了中国孤儿药研发策略。     

欧盟罕用药政策的分析及其对我国的启示

目的 通过分析欧盟及其成员国的罕用药相关政策,为我国罕用药及罕见病相关制度政策的制定提供参考。方法 采用文献研究法对欧盟及其成员国法国、意大利、荷兰、英国的罕用药相关政策进行检索,并比较分析四国相关政策与制度的异同点。结果 除欧盟统一的罕用药政策外,法国、意大利、荷兰以及英国均制定了相应的罕用药制度,设立罕见病治疗指导中心,有针对罕用药研发与价格制定的政策与措施,对于罕见病的治疗有相应的医疗保障制度,相应的政策制度较为完善。 结论 我国可借鉴其经验尽快制定罕见病的相关定义,建立罕见病中心,出台相应的研发激励与价格制定政策,并完善罕用药的报销与罕见病的医疗保障。     

罕见病药物市场与管理

罕见病,又称"孤儿病",是指发病率极低的疾病,绝大部分属于先天性疾病、慢性病,且常常危及生命。近年来,随着公众认知度的提高、国家政策的支持、诊断及治疗技术的进步,罕见病药物市场逐渐发展起来,销售额逐年增加,出现多个"重磅炸弹"级药物。国际大型药企开始抢占罕见病药物市场并且加紧药物研发,目前正在研发的罕见病药物有500多个,主要针对罕见癌症、遗传性疾病、神经类疾病、传染性疾病和自身免疫性疾病等。发达国家和地区在罕见病管理及市场发展方面都已经比较完善,而中国在这方面还比较落后。对中国罕见病药物市场的发展困境进行了分析并提出了几点建议,希望能够促进国内罕见病药物市场的快速发展。     

“孤儿药”激励机制亟待设立

在治疗罕见病的"孤儿药"的研发领域,一直活跃着许多新兴的中小型生物技术企业。而现在,随着越来越多的大型制药企业将研发重心转向孤儿药,这个领域呈现出群雄逐鹿的态势(见本期"产经"栏目)。对于我国的制药行业来说,这个领域也充满的着机会,因为在一定意义上来说,大家都处于同一起跑线上。但相比于发达国家日益健全的针对"孤儿药"研发的法规,我国在相关政策和立法上还处于起步阶段,如果不尽快推进相关法规和激励机制的设立,那必将制约中国     

让“孤儿”不再孤单

有这么一群弱小、无助的人,他们仿佛孤儿般被人们遗忘在社会角落的一旁。然而他们比孤儿更不幸与无奈,每天还得忍受着病魔带来的痛苦。这群人便是“罕见病患者”,他们不仅要承担病痛带来的折磨,而且还要面临着治疗难、     

eRepo-ORP: Exploring the Opportunity Space to Combat Orphan Diseases with Existing Drugs

About 7000 rare, or orphan, diseases affect more than 350 million people worldwide. Although these conditions collectively pose significant health care problems, drug companies seldom develop drugs for orphan diseases due to extremely limited individual markets. Consequently, developing new treatments for often life-threatening orphan diseases is primarily contingent on financial incentives from governments, special research grants, and private philanthropy. Computer-aided drug repositioning is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Here, we present eRepo-ORP, a comprehensive resource constructed by a large-scale repositioning of existing drugs to orphan diseases with a collection of structural bioinformatics tools, including eThread, eFindSite, and eMatchSite. Specifically, a systematic exploration of 320,856 possible links between known drugs in DrugBank and orphan proteins obtained from Orphanet reveals as many as 18,145 candidates for repurposing. In order to illustrate how potential therapeutics for rare diseases can be identified with eRepo-ORP, we discuss the repositioning of a kinase inhibitor for Ras-associated autoimmune leukoproliferative disease. The eRepo-ORP data set is available through the Open Science Framework at https://osf.io/qdjup/.     

Drug repositioning for orphan diseases

The need and opportunity to discover therapeutics for rare or orphan diseases are enormous. Due to limited prevalence and/or commercial potential, of the approximately 6000 orphan diseases (defined by the FDA Orphan Drug Act as <200 000 US prevalence), only a small fraction (5%) is of interest to the biopharmaceutical industry. The fact that drug development is complicated, time-consuming and expensive with extremely low success rates only adds to the low rate of therapeutics available for orphan diseases. An alternative and efficient strategy to boost the discovery of orphan disease therapeutics is to find connections between an existing drug product and orphan disease. Drug Repositioning or Drug Repurposing--finding a new indication for a drug--is one way to maximize the potential of a drug. The advantages of this approach are manifold, but rational drug repositioning for orphan diseases is not trivial and poses several formidable challenges--pharmacologically and computationally. Most of the repositioned drugs currently in the market are the result of serendipity. One reason the connection between drug candidates and their potential new applications are not identified in an earlier or more systematic fashion is that the underlying mechanism 'connecting' them is either very intricate and unknown or indirect or dispersed and buried in an ever-increasing sea of information, much of which is emerging only recently and therefore is not well organized. In this study, we will review some of these issues and the current methodologies adopted or proposed to overcome them and translate chemical and biological discoveries into safe and effective orphan disease therapeutics.     

Access to Orphan Drugs: A Comprehensive Review of Legislations,Regulations and Policies in 35 Countries

ObjectiveTo review existing regulations and policies utilised by countries to enable patient access to orphan drugs.MethodsA review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.ResultsFifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.ConclusionsOverall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.     

罕见疾病及孤儿药物研究现状及进展

文中简述了罕见疾病的定义、发病原因、分类,总结了国内外罕见疾病研究和孤儿药物研发的现状,分析了生物技术的研究手段在罕见疾病药物研发方面的应用,进一步阐述了罕见疾病研究和孤儿药物开发的必要性和紧迫性,对推动科学技术的进步和人类健康事业的发展具有深远的意义。     

Addressing the Unmet Medical Need for Safe and Effective Weight Loss Therapies

Obesity is a significant healthcare problem worldwide and increases the risk of developing debilitating diseases including type 2 diabetes, cardiovascular disease, and cancer. Although the health benefits of weight reduction are well‐recognized, weight loss by diet and exercise fail in most patients, and the current marketed drugs have had limited success. It is clear that there is a significant unmet medical need for safe and effective weight‐reducing agents. In this review, the current status of potential weight loss approaches that are in development by the pharmaceutical and biotechnology industry are discussed. This should lead to novel treatments that can be used long‐term to effectively treat this serious metabolic disorder.     

Development of health biotechnology in developing countries: Can private-sector players be the prime movers?

Health biotechnology has rapidly become vital in helping healthcare systems meet the needs of the poor in developing countries. This key industry also generates revenue and creates employment opportunities in these countries. To successfully develop biotechnology industries in developing nations, it is critical to understand and improve the system of health innovation, as well as the role of each innovative sector and the linkages between the sectors. Countries' science and technology capacities can be strengthened only if there are non-linear linkages and strong interrelations among players throughout the innovation process; these relationships generate and transfer knowledge related to commercialization of the innovative health products. The private sector is one of the main actors in healthcare innovation, contributing significantly to the development of health biotechnology via knowledge, expertise, resources and relationships to translate basic research and development into new commercial products and innovative processes. The role of the private sector has been increasingly recognized and emphasized by governments, agencies and international organizations. Many partnerships between the public and private sector have been established to leverage the potential of the private sector to produce more affordable healthcare products. Several developing countries that have been actively involved in health biotechnology are becoming the main players in this industry. The aim of this paper is to discuss the role of the private sector in health biotechnology development and to study its impact on health and economic growth through case studies in South Korea, India and Brazil. The paper also discussed the approaches by which the private sector can improve the health and economic status of the poor.     

Orphanet – das europäische Portal für seltene Krankheiten

Orphanet is a relational database of rare diseases and orphan drugs. This internet-based information platform was established jointly by the French Ministry of Health and the French National Institute of Health and Medical Research (INSERM) in 1997. Since 2000 Orphanet progressed as a European project. The concept was to provide all stakeholders with compiled information on rare diseases through a directory of expert services. This directory of services provides information on specialised outpatient clinics, clinical laboratories, research projects, registries, clinical trials and patient organisations from currently 38 countries. The Services are directly associated with the inventory of rare diseases; furthermore, a comprehensive encyclopaedia is available. All information is freely accessible in five languages at the website http://www.orpha.net.