(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.