Artesun®全球销量突破1亿支！复星医药“第一新药“帮助2000多万重症疟疾患者重获健康

2017-11-06 复星医药

2017年11月5日，复星医药成员企业桂林南药又迎来了一个里程碑——在疟疾治疗领域，其核心产品注射用青蒿琥酯自2010年通过世界卫生组织药品资格预审（WHO Prequalification of Medicines, WHO PQ认证）七周年之际，注射用青蒿琥酯Artesun®的全球销量累计已突破1亿支，帮助全球2000多万重症疟疾患者重获健康，其中大部分是5岁以下非洲儿童。

疟疾与结核，艾滋病并列为是世界三大传染病，全球约有半数人口面临疟疾风险，其中多数感染发生在撒哈拉以南非洲地区。2015年，约有2.12亿例疟疾病例，估计有42.9万例疟疾死亡1。疟疾通过携带疟原虫的蚊子在人群中传播。人一旦感染后将出现发烧、寒颤和呕吐等症状，如果不及时采取有效治疗措施，病情进展为重症疟疾后将引发贫血、昏迷、多脏器功能衰竭甚至死亡。

复星医药成员企业桂林南药是全球领先的抗疟药研发及生产制造企业，产品覆盖疟疾的预防、常规治疗和重症患者的抢救用药。为了帮助全球更多的重症疟疾患者远离死亡威胁，复星医药自2005年启动注射用青蒿琥酯（Artesun®）的WHO PQ认证，历时5年，Artesun®在2010年11月5日正式成为首个通过WHO PQ认证的重症疟疾治疗药物。

Artesun®（注射用青蒿琥酯）是复星医药拥有完全自主知识产权的创新药，也是首个获世界卫生组织推荐的重症疟疾一线治疗药物，更是目前国际上救治重症疟疾患者的金标准药物，现已在全球58个国家和地区广泛使用。

随着注射用青蒿琥酯及其它新型疟疾预防和治疗措施的推广，世界卫生组织在《2016年世界疟疾报告》中指出，自2010 年以来，全球特别是非洲地区的疟疾发病率和死亡率持续下降，全球各年龄组的疟疾死亡率降低了29%，5 岁以下儿童的疟疾死亡率降低了35%。

复星集团联席总裁、复星医药董事长陈启宇表示：

疟疾与世界上近一半人口的健康息息相关，更是受到国际社会广泛关注的全球公共卫生问题。复星医药一直将抗击疟疾作为企业社会责任的一部分，并将这一信念贯穿于我们抗疟药产品的整个生命周期。近年来Artesun®在非洲取得的成就让我们深受鼓舞。我们将持续为全球患者提供更多、更精准和更可负担的产品和服务，为共建一个‘无疟疾世界’而努力！

复星集团联席总裁、复星医药董事长陈启宇

在注射用青蒿琥酯Artesun®的整个产品生命周期中，复星医药对产品持续改进，不断提升其适用性和安全性。复星医药尤其关注儿童疟疾患者的需求，不仅开发了小规格的Artesun®，还根据儿童生理结构和成人的差异对20公斤以下儿童的用药剂量做了修订。复星医药是中国率先在国际上开展药品上市后药物安全性监测的本土制药企业之一，从2013 年开始为Artesun® 等具有自主知识产权的原研药产品建立了覆盖全球的药物安全警戒系统。

目前，Artesun®已取得37张海外注册证，在32个撒哈拉以南非洲国家注册销售，并通过以全球基金（The Global Fund to Fight AIDS, Tuberculosis and Malaria）、国际药品采购机制（UNTAID）、无国界医生组织（Médecins Sans Frontières, MSF）和中国政府的对外援助物资项目等国际药品援助项目全面进入疟疾流行国家和地区。注射用青蒿琥酯的推广使用为非洲疟疾疫区近年来的儿童疟疾死亡率降低做出了贡献，被评为“21世纪最经济有效的改善非洲儿童生命质量的措施”。

全球知名疟疾药物研发机构“疟疾药物风险开发基金“ （Medicinesfor Malaria Venture, MMV）的首席执行官David Reddy博士说：

注射用青蒿琥酯这一产品从根本上提高了濒临死亡的重症疟疾患者的生存率。我们的技术团队和全球资源配合复星医药帮助非洲的重症疟疾患者用上了这一挽救生命的药品。MMV为能和复星医药一起在全球公共卫生领域取得这项巨大成就而感到骄傲。

关于世卫组织药品资格预审（WHO Prequalificaiton of Medicines， WHO PQ认证）

为解决发展中国家用于治疗广泛流行性疾病的优质药品供应不足问题，自2001年起，世界卫生组织设立药品资格预审项目。WHO PQ认证团队通过对申请人提交的文件审核和现场评估，促进符合要求的低价高质药品的市场准入与采购，从而更好的挽救生命，服务公众健康。

关于Artesun®（注射用青蒿琥酯）

注射用青蒿琥酯是目前唯一商品化的青蒿素水溶性衍生物，可通过静脉和肌肉注射给药，用于各类人群的脑型疟疾和各种危重疟疾的治疗。多个大规模临床试验结果表明，注射用青蒿琥酯对特殊人群如孕妇和低龄儿童安全有效2, 5, 6。Artesun®于2010通WHO PQ认证，现已在全球37个国家注册销售，并通过“指定患者”项目等特殊药品供应渠道进入欧盟、加拿大、澳大利亚等法规市场7。

参考文献：

1.World Malaria Report 2016. Geneva: World HealthOrganization; 2016. Licence:CC BY-NC-SA 3.0 IGO.

2. Dondorp AM, Fanello CI, Hendriksen ICE, et al.Artesunate versusquinine in the treatment of severe falciparum malaria inAfricanchildren (AQUAMAT): an open-label, randomised trial. Lancet 2010;376:1647–57.

3. Lubell, Yoel et al. Cost-effectiveness of parenteralartesunate for treating children with severe malaria in sub-Saharan Africa. []., 89, 7, pp.504-512. ISSN 0042-9686.

4. Horton S, Gelband H, Jamison D, Levin C, Nugent R,Watkins D (2017) Ranking 93 health interventions for low- and middle-incomecountries by cost-effectiveness. PLoS ONE 12(8): e0182951.

5. World Health Organization, Guidelines for theTreatment of Malaria Third Edition, 2015

6. Stephanie D. Kovacs, Marcus J. Rijken, AndyStergachis, et al. Treating Severe Malaria in Pregnancy: A Review of theEvidence. Drug Saf 2015; 38:165–181, DOI 10.1007/s40264-014-0261-9.

7. Guideline on compassionate use of medicinal products,pursuant to Article 83 of Regulation (EC) no. 726/2004 (doc ref:EMEA/27170/2006). London: European Medicines Agency; 2007. Available from:http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004075.pdf [accessed 20 January 2011].

100 million vials of injectable artesunate distributed since 2010

MMV applauds landmark distribution of Guilin’s severemalaria treatment

06 Nov 2017

Photo: Damien Schumann

MMV welcomes the announcement by Fosun Pharma of theglobal distribution of 100 million vials of Artesun® (injectable artesunate –Inj AS), a life-saving treatment for severe malaria. The announcement of thislandmark achievement coincides with the 7^th anniversary of thedrug’s prequalification by the WHO in November 2010. Thanks to the use of InjAS instead of quinine per WHO’s recommendations, an estimated 650,000additional young lives may have been saved.

Severe malaria islife-threatening, especially in young children, and may ensue rapidly if a boutof uncomplicated malaria is not promptly treated.

MMV and Guilin Pharma, a member of Fosun Pharma, workedtogether to obtain WHO prequalification for the Inj AS formulation, Artesun. This – thefirst international stamp of approval for an Inj AS product – was granted inNovember 2010, and marked a critical turning point, making it possible for thefirst time for donor funds to support procurement of Inj AS as treatment forsevere malaria.

Since 2011, WHO’s Guidelines for the Treatment of Malaria (3^rd Edition) stronglyrecommends Inj AS as the preferred treatment for severe malaria based on theresults of the AQUAMAT¹ and SEAQUAMAT studies². These two ground-breakingstudies demonstrated the superiority of Inj AS over intravenous quinine,offering 23% and 35% reductions in mortality following treatment of severemalaria in African and Asian patients, respectively. A recent paper in PLoS ONE has also shown that Inj AS is one of 29most cost-effective health interventions to improve the quality of children’slives³.

“The tremendousaccomplishment of delivering 100 million vials of this life-saving medicine hasbeen achieved thanks to Fosun Pharma’s vision and long-standing commitment todeveloping WHO-prequalified medicines for malaria,” said Dr David Reddy, MMV’sCEO. “This commitment has helped radically to improve outcomes for criticallyill patients at risk of death from severe malaria. Fosun Pharma’s success isalso testament to the power of partnerships, with MMV bringing both technicalexpertise and its international network of donors and partners to the table,forging a long-lasting collaboration that successfully helped make this drugavailable to those in need. MMV is proud to be associated with this significantglobal health achievement.”

As of November 2017, Artesun remainsthe only WHO-prequalified Inj AS available. MMV is supporting efforts byadditional manufacturers to seek WHO prequalification for their Inj ASproducts, in order to create greater security and stability for the globalsupply of this critical medicine. In addition, MMV continues to evaluateopportunities to expand use of Inj AS in vulnerable populations; for example,recent policy reviews by MMV have revealed that, despite widespread adoption ofInj AS, many countries are still not aligned with WHO’s policy guidance thatthis drug should be used to treat severe malaria in all trimesters ofpregnancy. MMV’s commitment to ensure the maximum impact of this life-savingdrug will continue unabated in the years to come.

1. "Artesunate versusquinine for treatment of severe falciparum malaria: a randomised trial"N.J. White et al (South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT)group). The Lancet, volume 366: 717–25, August 27, 2005

2. "Artesunate versusquinine for treatment of severe falciparum malaria: a randomised trial"N.J. White et al (South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT)group). The Lancet, volume 366: 717–25, August 27, 2005

3. Horton S et al (2017) Ranking 93 health interventions for low- and middle-income countries bycost-effectiveness. PLoS ONE 12(8): e0182951.

https://www.mmv.org/newsroom/news/100-million-vials-injectable-artesunate-distributed-2010

100 million vials of Artesun® delivered to treat children with severemalaria

With MMV’s help, in November 2010, Guilin Pharmaceuticalbecame the first company to receive WHO prequalification¹ for their artesunateinjection for the treatment of severe malaria.¹ Since then, 100 million vialsof injectable artesunate have been delivered to malaria-endemic countries.Given that injectable artesunate offers a 22% reduction in mortality comparedto the alternative, quinine,² an estimated 650,000 additional young lives havebeen saved by this medicine over this time period^*.

Guilin Pharmaceutical has beenmanufacturing artesunate for injection since 1987. But without WHOprequalification or stringent regulatory approval, it could not be purchased byinternational organizations or with donor funds and was thus not reachingpatients with severe malaria. When approached by Guilin, MMV decided to use itsR&D know-how in a more unconventional way. Instead of developing a new productfrom scratch the team worked with Guilin to achieve WHO prequalification forthe existing medicine.

At the same time the results of the landmarkstudies AQUAMAT and SEAQUAMAT were released, whichdemonstrated the superiority of injectable artesunate over intravenous quininefor the treatment of severe malaria in African and Asian patientsrespectively. The WHO then promptly updated their guidelines to stronglyrecommend artesunate injection as first-line treatment in preference to quininefor the treatment of severe P. falciparum malariain adults and children.³

With the policy change inplace, MMV and partners developed plans to increase its uptake and use acrossthe malaria-endemic world. This involves advocacy work to ensure that evidenceis disseminated far and wide as well as developing and testing trainingmaterials to ensure ease of use in African healthcare settings. As a result,the number of malaria-endemic countries updating their guidelines to includeartesunate injection as an alternative to quinine continues to increase.

In December 2012, an MMV-ledconsortium was awarded a UNITAID grant of US$ 34 million to scale-up the use ofinjectable artesunate for severe malaria in disease-endemiccountries. This 3-year project which ended in June 2016 was built around aconsortium of implementing and procurement partners, with the participation ofCHAI, Malaria Consortium, and Missionpharma. The beneficiary countriesincluded: Cameroon, Ethiopia (SNNPR and OROMIA), Kenya, Malawi, Nigeria (13states) and Uganda. During the project, almost 6.0 million vials of treatmenthave been introduced across the multi-country project, a sufficient quantity totreat between 1.0 million and 1.5 million children. In addition, more than18,000 healthcare workers (at over 2,082 healthcare facilities) have beentrained during the ISMO project regarding the correct preparation andadministration of Inj AS.

Severe malaria is the condition that rapidly ensues if about of uncomplicated malaria is not promptly treated. Children areparticularly vulnerable since they have little or no immunity with which tofend off the parasite. The symptoms can include coma, severe breathingdifficulties, low blood sugar and severe anaemia, and if untreated, can lead todeath.⁴

Updated November 2017

1. World Health Organization fact sheet:Prequalification of medicines by WHO.

2. Dondorp AM et al. Artesunateversus quinine in the treatment of severe falciparum malaria in Africanchildren (AQUAMAT): an open-label, randomised trial. Lancet. 13;376(9753):1647-57 (2010).

3. World Health Organization Guidelines for thetreatment of malaria, 2nd edition – Rev. 1.

4. World Health Organization Management of SevereMalaria – A Practical Handbook.

https://www.mmv.org/our-impact/achievements/100-million-vials-artesun-delivered-treat-children-severe-malaria