2014年8月1日訊 /生物谷BIOON/ --諾華（Novartis）7月31日公布了實驗性抗瘧疾藥物KAE609（cipargamin）一項概念驗證臨床試驗的積極數據，有21例感染了惡性瘧原蟲（P.falciparum）或間日瘧原蟲（P.vivax）但無併發症的瘧疾患者參與了該項研究。研究人員發現，KAE609迅速清除了（平均12小時）無併發症瘧疾患者體內的惡性瘧原蟲和間日瘧原蟲，包括那些已產生抗性的瘧原蟲。相關數據已發表於《新英格蘭醫學雜誌》（New England Journal of Medicine）。
目前，諾華有2個在研的抗瘧疾候選藥物KAE609和KAF156，2者均屬於新一類的抗瘧疾化合物，作用機制與當前療法不同，對於防止不斷出現的耐藥性至關重要。此外，諾華也已確定PI4K是一個新的藥物靶標，有望用於預防、阻斷和治療瘧疾。
瘧疾是一種威脅生命的疾病，主要通過受感染按蚊的叮咬，將寄生蟲（惡性瘧原蟲和間日瘧原蟲）傳播給人類所導致。在全球範圍內，每年有超過60萬人死於瘧疾，其中大部分為非洲兒童。
在防治瘧疾的戰鬥中，KAE609有望成為一種改變遊戲規則的藥物。KAE609是首個螺吲哚酮類化合物，通過一種新穎的作用機制發揮抗瘧作用，KAE609的作用機制涉及抑制一種P型陽離子轉運體ATP酶4（PfATP4），在寄生蟲中，該酶調控鈉離子的濃度。鑑於KAE609似乎對瘧原蟲配子體也有效，因此該藥可能有助於防止疾病的傳播。而在體外試驗中，針對當前藥物已產生耐藥的多種寄生蟲，KAE609也表現出了強大的抗瘧活性。目前，諾華正在計劃開展IIb期臨床研究。（生物谷Bioon.com）
英文原文：KAE609 shows promise as next generation treatment for malaria
——KAE609 is the first antimalarial drug candidate with a novel mechanism of action to achieve positive clinical proof-of-concept in over 20 years
——KAE609 was tested in adult patients with uncomplicated malaria and showed a median parasite clearance time of 12 hours, including in patients with resistant infections[1]
——For more than a decade, Novartis has been a leader in the fight against malaria, setting the current gold standard for treatment and building one of the strongest malaria pipelines in the industry
Basel, Switzerland, July 30, 2014 - Today, Novartis published clinical trial results in the New England Journal of Medicine showing that KAE609 (cipargamin), a novel and potent antimalarial drug candidate, cleared the parasite rapidly in Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax) uncomplicated malaria patients[1]. Novartis currently has two drug candidates in development. Both KAE609 and KAF156 are new classes of anti-malarial compounds that treat malaria in different ways from current therapies, important to combat emerging drug resistance. Novartis has also identified PI4K as a new drug target with potential to prevent, block and treat malaria.
"Novartis is in the fight against malaria for the long term and we are committed to the continued research and development of new therapies to eventually eliminate the disease," said Joseph Jimenez, CEO of Novartis. "With two compounds and a new drug target currently under investigation, Novartis has one of the strongest malaria pipelines in the industry."
Malaria is a life-threatening disease primarily caused by parasites (P. falciparum and P. vivax) transmitted to people through the bites of infected Anopheles mosquitoes. Each year it kills more than 600,000 people, most of them African children[2].
"KAE609 is a potential game-changing therapy in the fight against malaria," said Thierry Diagana, Head of the Novartis Institute for Tropical Diseases (NITD), which aims to discover novel treatments and prevention methods for major tropical diseases. "Novartis has given KAE609 priority project status because of its unique potential of administering it as a single-dose combination therapy."
In June 2012, 21 patients infected by one of the two main malaria-causing parasite types took part in a proof-of-concept clinical study conducted in Bangkok and Mae Sot near the Thailand/Burma border where resistance to current therapies had been reported. Researchers saw rapid parasite clearance in adult patients (median of 12 hours)[2] with uncomplicated P. vivax or P. falciparum malaria infection including those with resistant parasites. No safety concerns were identified, however the study was too small for any safety conclusions.
"The growing menace of artemisinin resistance threatens our current antimalarial treatments, and therefore our attempts to control and eliminate falciparum malaria," said Nick White, Professor of Tropical Medicine at Mahidol University in Thailand and lead author of the NEJM article. "This is why we are so enthusiastic about KAE609; it is the first new antimalarial drug candidate with a completely novel mechanism of action to reach Phase 2 clinical development in over 20 years."
KAE609, the first compound in the spiroindolone class of treatment, works through a novel mechanism of action that involves inhibition of a P-type cation-transporter ATPase4 (PfATP4), which regulates sodium concentration in the parasite. Because KAE609 also appears to be effective against the sexual forms of the parasite, it could potentially help prevent disease transmission. The clinical trial was done in collaboration with the Wellcome Trust-Mahidol University - Oxford Tropical Medicine Research Programme. Research was supported by the Wellcome Trust, Singapore Economic Development Board, and Medicines for Malaria Venture.
KAE609 represents one of two new classes of antimalarial compounds that Novartis has discovered and published in the last four years.[3],[4] This drug candidate has shown potent in vitro activity against a broad range of parasites that have developed drug resistance against current therapies. KAE609 is currently being planned for Phase 2b trials.
This research is part of a broader commitment by Novartis in the fight against malaria. The Novartis Malaria Initiative focuses on improving access to treatment, helping communities in malaria-endemic countries deliver better healthcare and investing in research and development into the next generation of antimalarials. Over the past decade, the initiative has become one of the largest access-to-medicine programs in the healthcare industry, measured by the number of patients reached annually. In 2013, Novartis passed the mark of supplying 600 million treatments without profit to the public sector in endemic countries. For more information visit www.malaria.novartis.com.