Sumitomo Pharmaceuticals Co., Ltd.

在全球不同地方的监管机构中，由于制药企业研发战略定位、项目推进速度不同或者审批审批差异，导致新药上市存在着地区或者时间差异。笔者通过对过去10年欧美日上市新药检索分析，初步筛选了15款在日本已获批上市而在欧、美尚未上市，且在国内已被国家药品监督管理局指定为参比制剂的新药，可作为国内企业进行仿制药品种立项时的参考。Pivlaz（克拉生坦钠注射液）Pivlaz（克拉生坦钠注射液）是由瑞士Idorsia Pharmaceuticals公司开发的内皮素（ET）受体拮抗剂，用于预防颅动脉瘤(IA)所致蛛网膜下腔出血(aSAH)手术后的脑血管痉挛、血管痉挛相关的脑梗塞和脑缺血症状。IA是颅内动脉壁局限性､病理性扩张形成的动脉壁瘤状突出，80%的蛛网膜下腔出血由IA破裂引起，该类出血被称为aSAH｡据《重症动脉瘤性蛛网膜下腔出血管理专家共识(2023)》：世界范围内aSAH的年发病率在(2~16)/10万，占全部卒中患者的8%，而一项对500万中国成年人首次发生卒中后的死亡和复发性血管事件的社区研究报道显示，蛛网膜下腔出血患者占卒中的2%，女性较男性更易罹患蛛网膜下腔出血(女∶男=1.24∶1.0)，年龄为50岁及以上者为好发人群。目前常用的抗脑血管痉挛药物有钙通道阻滞剂——尼莫地平，2012年版美国心脏协会/美国卒中协会指南推荐所有aSAH患者应口服尼莫地平（Ⅰ级推荐，A类证据）｡对于无法口服给药的重症动脉瘤性蛛网膜下腔出血（SaSAH）患者，可考虑静脉用药，可选用药物如法舒地尔、西洛他唑、他汀类、克拉生坦、镁离子、尼卡地平、肝素等，均有用于治疗脑血管痉挛及迟发性脑缺血治疗的相关研究，被认为可能有防治迟发性脑缺血的作用，但尚无高等级证据证实其临床效果｡Pivlaz是从1997年开始着手开发，25年后才获批上市，原研1995年申请克拉生坦化合物专利并获授权（CN1098254 C），现该专利权已终止。而原研于2021年11月申请的克拉生坦二钠结晶水合物专利（CN116456984 A）目前正在实审中。Twymeeg（盐酸伊格列敏片）Twymeeg（盐酸伊格列敏片）是一种first-in-class类双重作用机制降糖药物，靶点为线粒体，通过葡萄糖浓度依赖性的胰岛素分泌促进作用和胰岛素抵抗性改善作用而发挥降血糖作用。伊格列敏在作为胰岛素分泌器官胰腺、及作为胰岛素靶器官的肝脏、骨骼肌等中作用于线粒体，用于促进葡萄糖浓度依赖性胰岛素分泌的胰腺发挥改善肝脏、骨骼肌的糖代谢的胰外作用（抑制糖新生、改善糖摄取能力）。伊格列敏是由Merck Serono（瑞士）开发，2009年Poxel SA公司（法国）获得许可，住友制药株式会社在2017年获得了日本国内开发和销售权。原研于2009年申请伊格列敏化合物专利（CN102245581 A）公布后视为撤回。伊格列敏是近年来批准为数不多的新机制糖尿病药物。Tarlige（苯磺酸米诺巴林片）Tarlige（苯磺酸米诺巴林片）是由第一三共株式会社开发的电位依赖性钙通道α2δ配体。α2δ配体被认为在突触前终末减少钙离子的流入，抑制兴奋性神经递质的释放，从而导致疼痛的缓解。米诺巴林通过α2δ特异性结合亚单位发挥镇痛作用。2019年1月，根据糖尿病周围神经性疼痛（DPNP）和带状疱疹后神经痛（PHN）患者的3期临床试验结果，Tarlige®片（苯磺酸米诺巴林片）在日本获批用于治疗“外周性神经性疼痛”。另外，作为包括日本在内亚洲地区的国际多中心试验，苯磺酸米诺巴林片治疗中枢性神经障碍性疼痛患者的3期试验有效性得到了验证，安全性得到了确认，适应症变更为“神经性疼痛”申请于2022年3月在日本获得批准。现有的研究表明，与普瑞巴林和加巴喷丁相比，米诺巴林在缓解DPNP和PHN相关疼痛方面具有较高的镇痛效果，其安全边际较宽，不良反应发生率相对较低。苯磺酸米诺巴林片适用的患者群体包括外周性神经障碍性疼痛患者和脑卒中患者，老年人较多。在这样的患者中，合并吞咽障碍的情况较多，普通片剂有时难以服药，还可能导致服药耐受性降低。第一三共株式会社又开发了苯磺酸米诺巴林口崩片（OD片）于2022年9月在日本获得了批准。而在国内，第一三共株式会社已完成了苯磺酸米诺巴林片（DS-5565）在糖尿病周围神经病变所致疼痛中国患者中的3期临床试验，有望很快提交上市申请。原研米诺巴林也在国内进行了全面布局，如核心化合物专利已在国内授权（CN101878193B），保护期到2028年9月，同时还布局了多件化合物或者中间体制备方法专利。米诺巴林还在制剂专利进行了布局：片剂（CN104334169B、CN107427483B、CN114786653A）和口崩片（CN115803020A）专利，亦获得授权或者实审中。慢性疼痛市场仍有一些未满足的需求。近年来，虽然有几种治疗慢性疼痛的药物获批上市，如礼来的Emgality（Galcanezumab）、灵北制药的Vyepti（Eptinezumab）等，主要为治疗偏头痛抗体药物。而米诺巴林作为该领域获批的口服镇痛药，不论给药途径，或是适应症方面都具有独特优势。Goofice（依洛昔巴特片）Goofice（依洛昔巴特片）由EAファーマ株式会社（从瑞典Albireo AB公司获得授权许可）开发全球首款获批上市胆汁酸转运抑制剂，用于治疗慢性便秘症。依洛昔巴特通过抑制调节胆汁酸重吸收的胆汁酸转运，从而增加患者体内胆汁酸流向结肠，进而促进肠道分泌更多的水分、促进排便，达到自然而然地改善患者自然排便通畅的效果。原研2001年申请依洛昔巴特化合物专利并获授权（CN1268618 C），现该专利权已终止。而原研于2014年申请的依洛昔巴特晶型专利（CN105143194 B、CN109096223 B）已授权，而结晶水合物专利（CN107001301 A、CN112375044 A）目前正在实审中。限于篇幅，本文仅是简单介绍，且不再对其他品种一一详述（具体品种见表1），对于感兴趣的品种，企业可自行深入调研或者关注[新药前沿]公众号留微信号联系笔者了解。本文由「新药前沿」微信公众号根据公开资料整理编辑，欢迎个人转发至朋友圈。媒体或机构转载授权请在「新药前沿」微信公众号留言公众号名称，审核通过后开通白名单获取转载授权，转载请标识来源。免责声明：本文仅作信息交流之目的，非投资建议或者治疗方案推荐，「新药前沿」微信公众号不对任何主体因使用本文内容而导致的任何损失承担责任。限于作者水平和专业知识所限，如有谬误，欢迎指正！

MISSISSAUGA, ON and KIRKLAND, QC, Oct. 19, 2023 /PRNewswire/ -- Sumitomo Pharma Canada, Inc. and Pfizer Canada today announced that Health Canada has granted a Notice of Compliance (NOC) for MYFEMBREE (Relugolix, estradiol and norethindrone acetate tablets) for the management of moderate to severe pain associated with endometriosis in pre-menopausal women on October 17, 2023. On September 22, 2023, Health Canada also approved MYFEMBREE for the management of heavy menstrual bleeding associated with uterine fibroids in pre-menopausal women. This combination therapy oral treatment is taken once daily and provides a new option for women to manage their symptoms related to endometriosis and uterine fibroids. "Health Canada's approval of MYFEMBREE across the uterine fibroid and endometriosis indications marks a significant milestone in our commitment to women's health," said Lisa Mullett, General Manager, Sumitomo Pharma Canada, Inc. "These are multi-faceted and complex chronic conditions, and we are proud to make new treatment options available to women in Canada." "MYFEMBREE's approval is a testament to the shared commitment between our two companies to support women's health," added Andréa Mueller, Primary Care Portfolio Lead at Pfizer Canada. "We are proud to help women manage their health at all stages of their lives." This approval is based on several comprehensive Phase 3 studies, including the LIBERTY 1 and LIBERTY 2 trials for uterine fibroids and the SPIRIT 1 and SPIRIT 2 trials for endometriosis. "Uterine fibroids and endometriosis are very common conditions affecting millions of Canadians. Endometriosis, in particular, can be a very challenging and complex condition to treat, often resulting in years of delay to diagnosis, said Dr. Sony Sukhbir Singh, Professor and Chair of the Department of Obstetrics and Gynecology, at the University of Ottawa. "These conditions can cause debilitating symptoms such as pain and bleeding, impacting daily life and overall well-being for many girls, women and gender diverse individuals." Following this approval Pfizer Canada will lead commercialization efforts of MYFEMBREE in the uterine fibroid and endometriosis indications. In partnership with Sumitomo Pharma in Canada, Pfizer Canada is currently assessing the timeline of availability for MYFEMBREE and are committed to bringing supply of this medicine to Canadians as quickly as possible. About Uterine Fibroids Uterine fibroids are the most common benign tumors in women of reproductive age.1 Uterine fibroids may be underdiagnosed due to several factors. Roughly 50 to 80% of women may have asymptomatic fibroids, meaning they don't experience noticeable symptoms. Additionally, some women with fibroid-related symptoms, such as heavy menstrual bleeding and pain, might not seek medical attention because they consider these issues to be a normal part of their menstrual cycles. Furthermore, healthcare providers may sometimes dismiss these symptoms as normal, contributing to the underestimation of uterine fibroid prevalence in Canadian women. 2,3,4,5 About Endometriosis Endometriosis is a chronic disease characterized by growth of endometrial-like tissue outside the uterus.6 This growth of endometriotic tissue relies on estrogen, a hormone crucial for regulating the female reproductive system.7 Endometriosis mainly affects women of reproductive age, occurring between their first menstrual period and menopause, when estrogen levels decline.8 In Canada, 7.0% of women aged 18-48 have endometriosis, with an average diagnosis age of 27.9. Most Canadian women experience symptoms before diagnosis with an average delay of 5.4 years in diagnosis.9 Symptoms include menstrual pain, pelvic pain, and pain during sex, with 60% reporting moderate to severe pain. 6,9,10 Endometriosis can impact fertility, quality of life, and work productivity.11 About MYFEMBREE® MYFEMBREE® (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) has received a dual indication approval, making it the first Health Canada-approved oral treatment to manage uterine fibroids and endometriosis. MYFEMBREE was approved by the U.S. Food and Drug Administration for the treatment of heavy menstrual bleeding associated with uterine fibroids in May 2021 and for the management of moderate to severe pain associated with endometriosis in August 2022. About Sumitomo Pharma Sumitomo Pharma Co., Ltd. is a global pharmaceutical company based in Japan with key operations in the U.S. (Sumitomo Pharma America, Inc.), Canada (Sumitomo Pharma Canada, Inc.) and Europe (Sumitomo Pharma Switzerland GmbH) focused on addressing patient needs in psychiatry & neurology, oncology, urology, women's health, rare disease, and cell & gene therapies. With several marketed products in the U.S., Canada, and Europe, a diverse pipeline of early- to late-stage assets, and in-house advanced technology capabilities, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information, please visit or follow us on LinkedIn. About Pfizer Canada Pfizer Canada ULC is the Canadian operation of Pfizer Inc., one of the world's leading biopharmaceutical companies. Our diversified healthcare portfolio includes some of the world's best known and most prescribed medicines and vaccines. We apply science and our global resources to improve the health and well-being of Canadians at every stage of life. Our commitment is reflected in everything we do, from our disease awareness initiatives to our community partnerships. To learn more about Pfizer Canada, visit pfizer.ca or you can follow us on LinkedIn, Facebook, Twitter or YouTube. 1 BMC Public Health, Global, regional, and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990–2019: an age-period-cohort analysis for the global burden of disease 2019 study, , Accessed August 22, 2023 2 Laberge PY, Vilos GA, Vilos AG, Janiszewski PM. Burden of symptomatic uterine fibroids in Canadian women: a cohort study. Curr Med Res Opin. 2016;32(1):165-75. doi:10.1185/03007995.2015.1107534 3 Bukulmez O, Doody KJ. Clinical features of myomas. Obstet Gynecol Clin North Am. Mar 2006;33(1):69-84. doi:10.1016/j.ogc.2005.12.002 4 Stovall DW. Clinical symptomatology of uterine leiomyomas. Clin Obstet Gynecol. Jun 2001;44(2):364-71. doi:10.1097/00003081-200106000-00022 5 Zimmermann A, Bernuit D, Gerlinger C, Schaefers M, Geppert K. Prevalence, symptoms and management of uterine fibroids: an international internet-based survey of 21,746 women. BMC Women's Health. Mar 26 2012;12:6. 6 Zondervan, K.T., et al., Endometriosis. Nat Rev Dis Primers, 2018. 4(1): p. 9. 7 Ahn, S.H., et al., Pathophysiology and immune dysfunction in endometriosis. BioMed research international, 2015. 2015. 8 Stratton, P. and K.J. Berkley, Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update, 2011. 17(3): p. 327-46. 9 Singh, S., et al., Prevalence, symptomatic burden, and diagnosis of endometriosis in Canada: cross-sectional survey of 30 000 women. Journal of Obstetrics and Gynaecology Canada, 2020. 42(7): p. 829-838. 10 Becker, K., et al., Real world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis. Scientific Reports, 2021. 11(1): p. 1-9. 11 Macer, M.L. and H.S. Taylor, Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstetrics and Gynecology Clinics, 2012. 39(4): p. 535-549. SOURCE Sumitomo Pharma America

Sunovion Pharmaceuticals Inc. (Sunovion) and Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka) today announced that the first patient has been randomized in SEP380-301, a Phase 3 clinical study evaluating non-racemic amisulpride (SEP-4199) for the treatment of major depressive episodes associated with bipolar I disorder (bipolar depression). Non-racemic amisulpride is being jointly developed and commercialized as part of a collaboration between Sunovion, its parent company Sumitomo Dainippon Pharma and Otsuka Pharmaceutical Co., Ltd. SEP380-301, named RELEASE 1 (NCT05169710), is a six-week, global, multicenter, randomized, double-blind, placebo-controlled, parallel-group study examining the efficacy, safety and tolerability of non-racemic amisulpride in adults with bipolar depression. Patients will be randomized to receive fixed-dose, non-racemic amisulpride (200 or 400 mg/day) or placebo. The primary endpoint for RELEASE 1 is the reduction of depressive symptoms, as measured by the change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, compared to placebo, after six weeks of treatment. Following participation in the six-week study period, patients who complete RELEASE 1 may enroll in RELEASE 3 (SEP380-303; NCT05227209), a 12-month, open-label extension study assessing the long-term safety, tolerability and effectiveness of non-racemic amisulpride. “Major depressive episodes associated with bipolar I disorder have a profound impact on those living with the condition. Depressive episodes are associated with mood impairment, fatigue, loss of interest in activities or social situations and, in some cases, suicidality,” said Armin Szegedi, M.D., Ph.D., Senior Vice President, Chief Medical Officer at Sunovion. “We are encouraged by our Phase 2 clinical results and look forward to enhancing our understanding of non-racemic amisulpride and its potential to help address unmet needs in the treatment of bipolar depression.” “Randomizing the first patient in the RELEASE Phase 3 clinical development program is a significant step in our collaboration with Sunovion and our shared goal of expanding neuropsychiatric treatment options to patients living with serious mental conditions,” said John Kraus, M.D., Ph.D., Vice President, Clinical Development Therapeutic Head, CNS, Otsuka Pharmaceutical Development & Commercialization, Inc. “Through our collaboration with Sunovion, we hope to advance SEP-4199, which we believe shows promise for the treatment of people with bipolar depression.” About Non-Racemic Amisulpride (SEP-4199) Non-racemic amisulpride (85:15 ratio of aramisulpride to esamisulpride; SEP-4199) is in Phase 3 clinical development for the treatment of major depressive episodes associated with bipolar I disorder (bipolar depression). Non-racemic amisulpride was designed to enhance 5-HT7 receptor antagonist activity and reduce dopamine D2 receptor antagonist activity compared to racemic amisulpride. Lower D2 receptor occupancy associated with non-racemic amisulpride is intended to maintain overall effectiveness for patients with mood disorders, including bipolar depression, while reducing the burden of D2-related side effects, including movement-related symptoms, such as extrapyramidal symptoms (stiffness, rigidity and tremor) and akathisia (restlessness).1 About Bipolar Disorder Bipolar disorder affects approximately 12.6 million individuals in the United States and an estimated 29 million people worldwide.2,3 A person is usually diagnosed with bipolar disorder after experiencing at least one manic/hypomanic episode, with symptoms that are not better explained by another mental health condition, such as schizophrenia.4 Bipolar disorder is characterized by debilitating mood swings, interspersed with periods of stable mood and behavior.5 When individuals with bipolar disorder are experiencing symptoms, most tend to be depressed rather than manic.4 Bipolar disorder is associated with significant impairment in personal and professional relationships, quality of life and ability to function.6 About Sunovion Pharmaceuticals Inc. (Sunovion) Sunovion is a global biopharmaceutical company focused on the innovative application of science and medicine to help people with serious medical conditions. Sunovion’s vision is to lead the way to a healthier world. The company’s spirit of innovation is driven by the conviction that scientific excellence paired with meaningful advocacy and relevant education can improve lives. With patients at the center of everything it does, Sunovion has charted new paths to life-transforming treatments that reflect ongoing investments in research and development and an unwavering commitment to support people with psychiatric, neurological and respiratory conditions. Headquartered in Marlborough, Mass., Sunovion is an indirect, wholly-owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. Sunovion Pharmaceuticals Canada Inc., based in Mississauga, Ontario, is a wholly-owned direct subsidiary of Sunovion Pharmaceuticals Inc. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: “Otsuka–people creating new products for better health worldwide.” Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 1,700 employees in the U.S. develop and commercialize medicines in the areas of mental health, nephrology, and cardiology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.3 billion in 2020. About Sumitomo Dainippon Pharma Co., Ltd. Sumitomo Dainippon Pharma is among the top-10 listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China, and other Asian countries. Sumitomo Dainippon Pharma aims to create innovative pharmaceutical products in the Psychiatry & Neurology area, the Oncology area and Regenerative medicine/Cell therapy field, which have been designated as the focus therapeutic areas. Sumitomo Dainippon Pharma is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, Sumitomo Dainippon Pharma has more than 7,000 employees worldwide. References 1 Hopkins SC, et al. Clin Pharmacol Ther. 2021;110(3): 808-815. 2 National Institute of Mental Health. Bipolar Disorder. [Internet]. Accessed March 17, 2016. 3 Swann A.C. Long-term treatment in bipolar disorder. J Clin Psychiatry. 2005; 66(1):7–12. 4 “Bipolar Disorder.” Decision Resources. Table 2-2. Burlington, MA. December 2013. 5 National Alliance on Mental Illness. The Impact and Cost of Mental Illness: The Case of Bipolar Disorder. [Internet]. Accessed March 17, 2016. 6 The Depression and Bipolar Support Alliance. Mood Disorders and Different Kinds of Depression. [Internet]. Accessed March 17, 2016.