S-1再創治療改變歷史! 2018美國臨床腫瘤年會（ASCO）與 日本臨床腫瘤年會 (JSMO) 雙雙 評為胃癌術後 重大改變治療指引“Practice Changing”

(エーブィエ バイオファーム 神戶 - 日本 2018.07.27 17:24 更新)   台灣、日本、中國、南美、東歐為胃癌高罹患率地區。可能的原因包含: 幽門螺旋桿菌感染、家族性多發性息肉症、抽煙、喝酒、高鹽、煙燻、醃漬食物等…，其中臨床可觀察到: 體重減輕、腹痛、噁心、嘔吐、厭食、吞嚥困難、解黑便、容易飽脹等症狀。然而胃癌通常有明顯症狀時已是晚期，治療效果有限。即使早期出現的症狀，與一般的消化性潰瘍症狀也難以區分，這也造成了胃癌患者存活率不好的原因。目前臨床指引，手術切除仍是根治胃癌的最主要手段。但由於胃癌術後復發率高，5年生存率只有五成左右，所以臨床治療一直在尋求除了手術以外治療胃癌的方法，進一步提升、改善胃癌患者的預後。

在現階段全球胃癌的臨床治療和研究中具有重大參考指標的日本胃癌學會（JGCA），自其第4版治療指南起，於胃癌術後輔助化療推薦在術後6周內服用S-1，並持續1年的治療。S-1是第四代的口服Fluoropyrimidine類藥品，單獨使用於胃癌化療反應率達30%，併用其它藥品時可高達60%。

在2007年ACTS-GC試驗發表在新英格蘭醫學期刊 (The New England Journal of Medicine, 簡稱NEJM) 之後，S-1成為第二、三期胃癌術後的標準治療，較單純手術組降低了33%的死亡風險，淋巴結和腹膜轉移復發風險也顯著降低，顯著延長了患者的術後生存。2017年ESMO會議上報告的JCOG1104（OPAS-1）研究顯示，使用S-1治療一年較使用半年更能延長患者生存期。

而2018年6月15日發表在NEJM的ASCO 2018 Report，更確認S-1為"改變治療指引的藥品"(Practice Changing) 。

因為在一個大型的138所臨床試驗中心執行的研究 (簡稱JACCRO GC-07 trial) 中，S-1加上Docetaxel合併治療 (oral S-1 at 80-120mg/body on days 1-14 with 7 days of rest was followed by 6 cycles of S-1 at the same dosage and schedule combined with docetaxel 40mg/m2 on day 1 of each cycle, and then 4 further cycles of S-1 at 80-120mg/body on days 1-28 every 42 days)，發現在915位病人人中，可顯著提升第三期胃癌3年無復發存活期 16% (65.9% vs. 49.5%; HR=0.632; P=0.0007)! 觀察發現，S-1加上Docetaxel合併治療，除顯著提高存活期外，並能有效抑制經血液,淋巴或腹膜轉移復發風險，此令人振奮的大型胃癌術後的臨床試驗結果，提供給未來治療的有效參考依據。

Otsuka 投資Visterra公司 $430M (484億円)強化 感染與流感 治療領域: APRIL/ IL-2R/ C5a receptor/ C3 convertase

【大塚製薬】米ベンチャー「ビステラ」、484億円で買収‐抗体創薬基盤を獲得

( エーブィエ バイオファーム) 2018年7月19日 (木) 大塚製薬は、米マサチューセッツ工科大学発バイオベンチャー「ビステラ」を4億3000万ドル（約484億円）で買収する。大塚の米国法人（OAI）を通じてビステラを完全子会社化することで合意し、必要な手続きを得て9月までに買収が完了する予定だ。従来の低分子創薬に加え、ビステラの抗体創薬基盤や、難病の一種であるIgA腎症治療薬「VIS649」など複数の前臨床段階のパイプラインを獲得する。ビステラは、2007年にマサチューセッツ工科大学からスピンアウトして設立されたバイオベンチャーで、独自の抗体プラットフォーム技術「ヒエロトープ・プラットフォーム」を有するほか、腎疾患や癌、神経疾患、感染症で、前臨床段階の化合物や特定のターゲットに対する探索研究案件を複数持つ。従業員48人のほとんどが研究者だ。

Otsuka to Acquire Visterra for $430M, Adding to Its Pipeline and Platforms Alex Philippidis An illustration of Visterra's Hierotope® platform, intended to design and engineer precision antibody-based therapies that target epitopes deemed critical to the structural and functional integrity of disease pathogens. Otsuka Pharmaceutical has agreed to acquire Visterra for $430 million. [Visterra]  Otsuka Pharmaceutical has agreed to acquire Visterra for approximately $430 million cash, the companies said today, in a deal that expands the pipeline of Otsuka and aligns with its goal of enhancing its drug discovery and development platforms.  Through the acquisition, Otsuka will inherit Visterra's Hierotope® platform, intended to design and engineer precision antibody-based therapies that specifically bind to, and modulate, disease targets not adequately addressed by current technologies. Hierotope uses novel computational and experimental technologies, particularly atomic interaction network (AIN) analysis, to both identify hierotopes—epitopes deemed critical to the structural and functional integrity of disease pathogens—then design and engineer treatments that target these epitopes.  The deal will also expand Otsuka's pipeline with Visterra's programs targeting infectious diseases, kidney diseases, cancer, and chronic pain. Otsuka said these therapeutic areas complement its own areas of focus—which are led by two "core" areas, the central nervous system and oncology, and include the cardiovascular system, gastroenterology, the respiratory system, infectious disease, ophthalmology, dermatology, allergies, and urology. Visterra's lead program, and its only clinical-phase program, is the infectious disease candidate VIS410 (hemagglutinin), a Phase II monoclonal antibody designed to treat hospitalized patients with influenza A. Visterra is recruiting patients for a Phase II study (NCT03040141) assessing the combination of VIS410 with Tamiflu® (oseltamivir) in hospitalized adults with influenza A who require oxygen support, as of the most recent trial update posted April 18 on ClinicalTrials.gov.  In 2015, Visterra won a five-year, up-to-$204.5 million contract from the Biomedical Advanced Research and Development Authority (BARDA) toward the development of VIS410. VIS410 anchors Visterra's infectious diseases portfolio, which includes preclinical candidates VIS513 for dengue fever, and VIS705 for severe Pseudomonas Aeruginosa infection.  In October 2017, Visterra launched a potentially more-than-$1 billion collaboration with Vir Biotechnology to develop up to six antibodies to treat infectious diseases. Under that agreement, Vir has an option to join Visterra in developing and commercializing VIS410, while the companies agreed to advance three infectious disease antibodies developed with Hierotope, including antibodies against influenza, RSV, and fungal infections. Vir also has the right to launch two additional research programs to develop antibodies against pathogens of its choosing. 

Targeting APRIL Visterra's kidney disease portfolio is led by the Imumuglobulin A Nephropathy candidate VIS649, which is designed to target the cytokine A Proliferation Inducing Ligand (APRIL); and preclinical candidates targeting the interleukin-2 receptor (IL-2R), the complement C5a receptor (C5aR), and C3 convertase. Also in the company's preclinical pipeline are a CD138-targeting candidate for smoldering multiple myeloma, and a chronic pain candidate designed to target the sodium ion channel Nav1.7.  Also last October, Visterra completed a $46.7 million Series C financing, consisting of an extension totaling $23.6 million designed to advance the development of Hierotope, VIS410, and VIS649, in addition to the initial $23.1 million raised in June 2016. New investors Serum Institute of India Pvt. Ltd., CTI Life Sciences and Allegheny Financial Group joined existing investors that included the Bill & Melinda Gates Foundation, MRL Ventures Fund, Vertex Venture Holdings, Polaris Partners, Flagship Pioneering, Omega Funds, Cycad Group, and Alexandria Venture Investments."Our two companies share a common culture of creativity and innovation, and commitment to patients with kidney diseases, cancer, and other hard-to-treat diseases. Joining forces with Otsuka will provide Visterra the resources, support, and commitment to accelerate development of our pipeline and fully realize the potential of our technology platform," Visterra CEO Brian J. G. Pereira, M.D., said in a statement. "This transaction affirms the power of Visterra's novel technology platform, the promise of our product candidates, and the value our employees and shareholders have created." Following completion of the acquisition, Visterra will be a wholly-owned subsidiary of Otsuka, and will retain its staff and operations in Waltham, MA, the companies said. The boards of Otsuka and Visterra have approved the transaction, which is expected to close in the third quarter subject to customary closing conditions, including expiration or termination of the waiting period under U.S. antitrust laws. 

Visterra is one of two acquisitions announced by Otsuka this week. Otsuka yesterday said it is buying medical device maker ReCor Medical for an undisclosed price. The deal follows FDA approval June 15 of the RADIANCE II pivotal clinical study to assess the Paradise® Renal Denervation System, an ultrasound ablation system designed for safe and effective reduction of blood pressure in patients with hypertension. The study is set to start enrolling patients in October.