塩野義製薬 全新流感藥物 公布臨床三期 數據: 台灣藥證核可 拚領先美國 !!

Shionogi Announces Positive Top-Line Results for Baloxavir Marboxil Phase III Study (CAPSTONE-2) in Individuals at High Risk for Influenza-Related Complications OSAKA, Japan, July 17, 2018 - Shionogi & Co., Ltd. (hereafter "Shionogi") has announced that the global phase III study (CAPSTONE-2) assessing baloxavir marboxil in individuals at high risk for influenza-related complications met the study's primary objective and showed superior efficacy in the primary endopoint of time to improvement of influenza symptoms compared with placebo. Baloxavir marboxil also demonstrated superior efficacy compared with placebo and compared with oseltamivir in key secondary endpoints, including reducing the time that the virus was released (viral shedding), and reducing viral levels in the body. Furthermore, baloxavir marboxil significantly reduced the incidence of influenza-related complications compared to placebo. Baloxavir marboxil was well tolerated and no safety signals were identified. The results from the CAPSTONE-2 study will be presented at upcoming medical meetings. Baloxavir marboxil has a novel mechanism of action that inhibits cap-dependent endonuclease, an essential enzyme for viral replication. Baloxavir marboxil has already demonstrated a clinically significant benefit over both placebo and oseltamivir in the global phase III study in otherwise healthy patients (CAPSTONE-1). 1, 2 Baloxavir marboxil was approved in Japan on February 23, 2018 and is available under the brand name XOFLUZA® for the treatment of influenza Types A and B in adults and pediatric patients.3 Shionogi submitted the New Drug Application (NDA) for baloxavir marboxil in U.S. on April 24, 2018 for the treatment of acute uncomplicated influenza in patients 12 years of age and older and the U.S. Food and Drug Administration (FDA) recently accepted the NDA and granted Priority Review. The Prescription Drug User Fee Act (PDUFA) date for an FDA decision is December 24, 2018.4 Shionogi submitted a NDA for baloxavir marboxil in Taiwan on June 29, 2018, for the treatment of influenza in patients 12 years of age and older. 5 The data from the CAPSTONE-2 study demonstrate that baloxavir marboxil provides a clinically meaningful benefit for patients who are most susceptible to influenza-related complications. There are no medicines which have demonstrated clear benefit specifically in high-risk populations in clinical studies. "Following the successful Phase III study reported previously in otherwise healthy patients, this study showed a positive result in high risk patients, including those with asthma or chronic lung disease, endocrine disorders, heart disease, metabolic disorders and morbid obesity or those who are 65 years of age or older, who tend to develop complications with influenza. We believe that baloxavir marboxil has the potential to offer an improved treatment for influenza for a wider patient population." said Dr. Tsutae Den Nagata, Chief Medical Officer.

【塩野義製薬】便秘薬「シンプロイック」、米国で共同販促を解消

( エーブィエ バイオファーム) 2018年7月17日 (火)塩野義製薬は、米国で販売しているオピオイド誘発性便秘症治療薬「シンプロイック」（一般名：ナルデメジン）について、米パデューファーマとの共同販促を解消し、米国での全権利を再取得した。既に自社販売と流通を開始しており、現在は新たなパートナー企業を選定中。塩野義は2016年12月に、パデューファーマとシンプロイックの米国販売で事業提携を行うことに合意。米オピオイド鎮痛薬市場でトップシェアを有するパデューファーマの販路の活用を図っていた。

(塩野義製薬 & Purdue): Re-acquisition of all rights relating to Symproic(R) for opioid-induced constipation treatment in the United States

( エーブィエ バイオファーム )米国におけるオピオイド誘発性便秘症治療薬 Symproic®に関する 全権利の再取得について塩野義製薬株式会社2018 年7月6日（本社：大阪市中央区、代表取締役社長：手代木 功、以下「塩野義製薬」）は、当社が創製したオピオイド誘発性便秘症治療薬 Symproic®（一般名：ナルデメジン錠、0.2 mg） について、米国における戦略的提携先のPurdue Pharma 社（以下、Purdue 社）から全ての権利 を再取得したことを、お知らせいたします。 本件は、Purdue 社が事業環境変化に対応するために米国内のビジネスモデルを変革し多様化さ せることを受けたものであり、塩野義製薬とPurdue 社は Symproic®の米国における共同販売活 動に関するアライアンス活動を終了することで合意しております。この件に関し、塩野義製薬には、Purdue 社に対するいかなる金銭的およびその他の義務も発生いたしません。塩野義製薬は、Symproic®の自社販売と流通を既に開始し、販売促進のための新たなパートナ ー企業を選定中です。米国におけるオピオイド誘発性便秘症（OIC）患者数は数百万人にも上る ことから、Symproic®は OIC でお困りの患者さまに対する重要な治療選択肢の一つであると確信 しております。塩野義製薬は、中期経営計画『SGS2020』で経営資源を集中するコア疾患領域のひとつに疼痛領域を選択し、疼痛治療に関する諸課題を解決する革新的新薬の創製に注力しております。引き 続き疼痛領域に対する取り組みを強化し、さまざまな痛みや疼痛治療薬による副作用でお困りの 患者さまの QOL（quality of life）向上に貢献してまいります。

Fifty-Two Week Safety Study on Symproic® (naldemedine) for Opioid-induced Constipation (OIC) in Adults with Chronic Non-cancer Pain Published in PAIN First 52-Week Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of a Peripherally-acting Mu-opioid Receptor Antagonist (PAMORA)  March 06, 2018 08:30 AM Eastern Standard Time OSAKA, Japan & FLORHAM PARK, N.J. & STAMFORD, Conn.--(BUSINESS WIRE)--Shionogi Inc. and Purdue Pharma L.P. today announced the publication of a study known as COMPOSE-3. The study is the first to investigate a peripherally-acting mu-opioid receptor antagonist (PAMORA) over the course of 52 weeks in a randomized, placebo-controlled and double-blind manner. The study was published online ahead of print in PAIN, the journal of the International Association for the Study of Pain. "We are pleased to share with the scientific community the publication of the first 52-week double-blind study evaluating the safety of a PAMORA in adult patients with OIC and chronic non-cancer pain""The publication of the results of COMPOSE-3 in PAIN is significant as the study provides additional important information regarding the safety and tolerability of Symproic over the course of 52 weeks for adults with OIC and chronic non-cancer pain," said Dr. Tsutae "Den" Nagata, Chief Medical Officer, Shionogi.

Study Design and Results This randomized, double-blind, placebo-controlled, parallel-group, Phase 3 clinical trial (COMPOSE-3) evaluated the long-term safety and tolerability of once-daily oral Symproic 0.2 mg for 52 weeks in patients with chronic non-cancer pain, on a stable opioid therapy, and who could be on a routine laxative regimen but still had OIC. In the study, 2,414 patients were screened. Patients had to be aged 18 to 80, have had chronic non-cancer pain for at least 3 months, were receiving a stable daily dose of opioids (greater than or equal to 30 mg oral morphine equivalents) for at least one month prior to screening, and had self-reported OIC. From the patients screened, 1,246 eligible patients with confirmed OIC were randomized 1:1 to receive once-daily oral Symproic 0.2 mg (n=623) or placebo (n=623) for 52 weeks.  The primary endpoint was summary measures of treatment-emergent adverse events (TEAEs). Similar proportions of patients taking Symproic and placebo experienced TEAEs (Symproic, 68.4% (n=425) vs placebo 72.1% (n=446); difference: −3.6% [95% CI: −8.7-1.5]) and TEAEs leading to study discontinuation (Symproic 6.3% vs placebo 5.8%; difference: 0.5% [95% CI: –2.2-3.1]). Diarrhea was the most common TEAE in the Symproic group (11%) and was reported more frequently vs placebo (5.3%; difference: 5.6% [95% CI: 2.6-8.6]). A greater proportion of patients treated with Symproic vs placebo reported other gastrointestinal-related treatment-emergent adverse events, including abdominal pain (8.2% vs 3.1%) and vomiting (6.0% vs 3.1%). The incidences of treatment-related serious adverse events (Symproic, 0.5% vs placebo, 1.0%; difference: −0.5% [95% CI: −1.4-0.5]) and serious TEAEs leading to study discontinuation (Symproic, 1.1% vs placebo, 1.9%; difference: −0.8% [95% CI: −2.2-0.6]) were consistent between treatment groups. The 52-week safety study included efficacy endpoints as well, which were secondary. One of these endpoints, frequency of bowel movements, was also assessed in the primary endpoint of the two 12-week pivotal studies, and the results were consistent. "We are pleased to share with the scientific community the publication of the first 52-week double-blind study evaluating the safety of a PAMORA in adult patients with OIC and chronic non-cancer pain," said Monica Kwarcinski, PharmD, Head of Medical Affairs, Purdue Pharma L.P. "In collaboration with our partners at Shionogi, we are committed to supporting adult patients who live with OIC and chronic non-cancer pain and the physicians who treat them." 

Symproic, a once-daily oral PAMORA medication approved by the U.S. Food and Drug Administration (FDA) in March 2017, is indicated for the treatment of OIC in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Symproic is available as a 0.2 mg once-daily oral tablet and may be taken at any time of day, with or without food, and with or without laxatives. Alteration of analgesic dosing regimen prior to initiating Symproic is not required. Patients receiving opioids for less than 4 weeks may be less responsive to Symproic. Treatment with Symproic should be discontinued if treatment with the opioid medicine is also discontinued. 

INDICATION Symproic® (naldemedine) is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

(エーブィエ バイオファーム) 20 年來 全新抗 "流感" 藥上市 ! Faster than FDA，New Mechanism flu medicine（Baloxavir marboxil） intending approved in Taiwan/ 塩野義製薬、新規インフルエンザ治療薬「バロキサビル マルボキシル」を台湾で製造販売承認申請

Shionogi Filed for the New Drug Application of Baloxavir Marboxil in Taiwan for the Treatment of Influenza OSAKA, Japan, July 2, 2018 - Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President and CEO: Isao Teshirogi, Ph.D.; hereafter "Shionogi") today announced that Shionogi filed the New Drug Application (NDA) of baloxavir marboxil in Taiwan for the treatment of influenza in patients 12 years of age and older on June 29, 2018. Baloxavir marboxil has a novel mechanism of action that inhibits cap-dependent endonuclease, an essential enzyme for viral replication. Baloxavir marboxil was approved in Japan on February 23, 2018 and is available under the brand name XOFLUZATM for the treatment of influenza Types A and B in adults and pediatric patients. 1 Clinical efficacy and safety data from a phase II study in Japan and a global phase III study (CAPSTONE-1) in otherwise healthy patients supported this NDA. Shionogi and F. Hoffmann-La Roche Ltd. (hereafter "Roche") are in a license and collaboration agreement to further develop and commercialize baloxavir marboxil. Under the terms of this agreement, Roche holds worldwide rights to baloxavir marboxil excluding Japan and Taiwan where the rights are retained exclusively by Shionogi. Shionogi is currently conducting a global Phase III study (CAPSTONE-2) in individuals at high risk for influenza-related complications. Shionogi's research and development efforts target infectious diseases as one of its priority areas, and Shionogi has positioned "protecting people from the threat of infectious diseases" as one of its core social missions. Shionogi strives constantly to bring forth innovative drugs for the treatment of infectious diseases, to protect the health of the many patients we serve.

2018/7/2 発表日：2018年7月2日塩野義製薬株式会社（本社：大阪市中央区、代表取締役社長：手代木 功、以下「塩野義製薬」または「当社」）は、バロキサビル マルボキシル（日本における製品名：ゾフルーザ(TM)）について、12歳以上の合併症のないインフルエンザウイルス感染症を適応症として、2018年6月29日に台湾食品薬物管理局（TFDA）に新薬承認申請を行いましたので、お知らせいたします。バロキサビル マルボキシルは、既存の薬剤とは異なる新しい作用機序であるキャップ依存性エンドヌクレアーゼ阻害作用でインフルエンザウイルスの増殖を抑制します。本薬は2018年2月23日に日本国内で製造販売承認を取得し、成人および小児におけるA型およびB型インフルエンザ感染症を対象に製品名ゾフルーザ(TM)として販売されております1。このたび、重症化および合併症を起こしやすいリスク要因を持たない健常のインフルエンザ患者を対象とした国内第II相臨床試験およびグローバル第III相臨床試験（CAPSTONE-1）における良好な有効性および安全性の結果をもとに、TFDAに新薬承認申請を行いました。本薬の開発および販売はF. Hoffmann-La Roche Ltd.（以下「Roche社」）との提携下で進めており、日本と台湾における本薬の販売は塩野義製薬が、それ以外の国における本薬の販売はRoche社が行います。現在、重症化および合併症を起こしやすいリスク要因を持つ患者を対象としたグローバル第III相臨床試験（CAPSTONE-2）を当社が実施中です。塩野義製薬は「創薬型製薬企業として社会とともに成長し続ける」ことを経営目標として掲げた中期経営計画SGS2020の中で、「世界を感染症の脅威から守る」ことを当社が取り組むべき社会課題の一つにあげております。人々の健康を守るために必要な感染症治療薬を、世界中の患者さまのもとにいち早くお届けできるよう、引き続き努力してまいります。なお、本件が2019年（平成31年）3月期の業績に与える影響はありません。

FDA grants priority review to novel flu antiviral June 27, 2018 Genentech announced that the FDA has accepted a new drug application and granted priority review for the company's single-dose, oral influenza treatment baloxavir marboxil. The investigational medication is designed to inhibit the cap-dependent endonuclease protein crucial for influenza virus replication, including in oseltamivir-resistant and avian strains, according to a news release. It is intended for patients aged 12 years and older with acute, uncomplicated influenza. Genentech said the FDA is expected to make a decision on the approval of baloxavir marboxil by Dec. 24. If approved, it would be the first influenza treatment with a novel mechanism of action in almost 20 years, the release said."The severity of the recent flu season underscores the need for new options beyond currently available treatments," Sandra Horning, MD, chief medical officer and head of global product development at Genentech, said in the release. "Baloxavir marboxil has been shown in clinical trials to decrease the duration of symptoms with one dose and demonstrated a significant reduction in viral shedding in just 1 day. We look forward to working with the FDA during the review process." The new drug application (NDA) is based on phase 3 data from CAPSTONE-1, a multicenter, randomized, double blind trial conducted in the United States and Japan. The trial compared the safety and efficacy of baloxavir marboxil with placebo or 75 mg of oseltamivir twice a day for 5 days in 1,436 patients aged 12 to 64 years with uncomplicated influenza. According to results presented at IDWeek, it was associated with a shorter duration of influenza symptoms compared with placebo — 53.7 hours vs. 80.2 hours (P < .0001) — and reduced the time to resolution of fever, which took 24.5 hours vs. 42 hours for placebo. There was no significant difference in the duration of symptoms or fever between the baloxavir marboxil and oseltamivir groups.  In other results, the median time to the cessation of viral shedding was 24 hours in patients who received baloxavir marboxil, 72 hours in patients who received oseltamivir (P < .0001) and 96 hours in those who received placebo (P < .0001). In addition, baloxavir marboxil significantly reduced viral titers in the nose and throat from 24 hours through 120 hours compared with placebo, and at 24 hours and 72 hours compared with oseltamivir, the release said.  In a safety analysis, baloxavir marboxil was well-tolerated and had a lower overall incidence of treatment-emergent adverse events (20.7%) compared with oseltamivir (24.8%) and placebo (24.6%). The most common adverse events reported by patients in the baloxavir marboxil group were diarrhea (3%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%). The NDA is also supported by data from a phase 2, placebo-controlled study in otherwise healthy patients with influenza, according to the release. Baloxavir marboxil will continue to be assessed during a phase 3 development program. Genentech said findings from the CAPSTONE-2 trial, which includes adult and pediatric patients at high risk for influenza complications, will be announced at a later date. The Roche Group, which includes Genentech, is developing baloxavir marboxil globally under an agreement with Shionogi & Co., Ltd., which discovered the treatment. Roche holds rights to baloxavir marboxil worldwide, except for in Japan and Taiwan. In these countries, rights to the antiviral are held exclusively by Shionogi. In February, the Japanese Ministry of Health, Labor and Welfare approved balaxovir marboxil for adult and pediatric patients with influenza types A and B. It is sold under the brand name Xofluza. 

References: Genentech. FDA Grants Priority Review to Genentech's Baloxavir Marboxil for the Treatment of Influenza. https://www.gene.com/media/press-releases/14732/2018-06-25/fda-grants-priority-review-to-genentechs. Accessed June 26, 2018.