拜耳向EMA提交Stivarga治疗GIST新适应症申请

   拜耳（Bayer）9月5日宣布，已向欧洲药品管理局（EMA）提交了口服多激酶抑制剂Stivarga（regorafenib）的上市许可申请（MAA），寻求批准用于既往经2种酪氨酸激酶抑制剂（Gleevec、Sutent）治疗后病情恶化或不能手术切除的胃肠道间质瘤（GIST）患者的治疗。此前，Stivarga于2013年8月30日获EMA批准用于转移性结直肠癌（mCRC）的治疗。

目前，Stivarga已获美国、欧盟、日本批准，用于转移性结直肠癌（mCRC）的治疗。同时，该药已获美国和日本批准用于治疗胃肠道间质瘤（GIST）。

Stivarga是FDA批准的第三个治疗胃肠道间质瘤（GIST）的药物，另2个药物为诺华的格列卫（Gleevec）、辉瑞的索坦（Sutent）。

胃肠道间质瘤（GIST）是癌细胞发生在胃肠道的一种肿瘤，患者多为老年人。GIST，由于其极具侵略性的特点，目前依然是尚未满足的医疗需求，同时治疗的选择也很有限，相关临床研究数据表明，Stivarga有望为那些经标准治疗后复发的患者提供一种重要的治疗方案。

Stivarga是一种口服多激酶抑制剂，在临床前研究中，regorafenib能够抑制数个促血管生成VEGF受体酪氨酸激酶，这些激酶在肿瘤的血管生成中发挥着重要作用。该药还可以抑制癌和肿瘤微环境中的多种激酶，包括VEGFR 1-3, KIT, RET, PDGFR及FGFR。

Stivarga由拜耳开发，由拜耳和Onyx制药联合推广。

英文原文阅读

Bayer’s Regorafenib Submitted for European Marketing Authorization for the Treatment of Gastrointestinal Stromal Tumors (GIST)

EMA filing follows EU approval of Stivarga? (regorafenib) for use in metastatic colorectal cancer

Berlin, September 5, 2013 – Bayer HealthCare has submitted an application for marketing authorization to the European Medicines Agency (EMA) for the oral multi-kinase inhibitor, regorafenib, for the treatment of patients with gastrointestinal stromal tumors (GlST) who have been previously treated with two tyrosine kinase inhibitors. The EMA filing follows the EU approval of regorafenib (Stivarga?) for use in metastatic colorectal cancer in August 2013.

“The submission of regorafenib to EMA is an exciting advance because it means patients with GIST will have a potential new treatment option to help manage an aggressive disease”, said Kemal Malik, M.D., Member of the Bayer HealthCare Executive Committee and Head of Global Development. “We look forward to offering patients and physicians a new path forward.”

“GIST is a disease that only affects a limited number of people, about 15 per million per year. However, of those who are affected over half develop recurrent metastatic disease, for which there are currently very few treatment options once resistance to first line treatments are observed”, said Prof. Jean-Yves Blay, M.D., Ph.D, University Claude Bernard Lyon, Centre Léon Bérard, Department of Medicine, French Sarcoma Group (GSF-GETO), European Organisation for Research and Treatment of Cancer (EORTC). “The results from the GRID study suggest a significant progression free survival benefit for patients with GIST who have been treated with regorafenib.”

Stivarga is approved in the USA, Europe and Japan, for the treatment of patients with metastatic colorectal cancer (mCRC). Stivarga has also been approved in the USA and Japan for the treatment of GIST.

About Gastrointestinal Stromal Tumors (GIST)

GIST is the most common form of sarcoma arising from the muscle wall of the gastrointestinal tract. GIST represents a life-threatening malignancy if the disease has spread to other parts of the body (metastasized) or is unable to be surgically removed with curative intent. The incidence of GIST is estimated to be 1.5 cases per 100,000 people in Europe. At the point of diagnosis, an estimated 10-25 percent of GIST cases have disease that has metastasized.

The discovery of oncogenic KIT kinase mutations in GISTs and the introduction of kinase inhibitor therapies have led to a rapid evolution in the understanding of these tumors. It is now established that 70-80% of GISTs harbor a KIT gene mutation, that these mutations lead to the continued activation of the kinase and that mutant KIT is a clinically important therapeutic target in GIST.

About regorafenib (Stivarga?)

Stivarga? is an oral multi-kinase inhibitor that inhibits various kinases within the mechanisms involved in tumor growth and progression – angiogenesis, oncogenesis and the tumor microenvironment. In preclinical studies, Stivarga inhibits several angiogenic VEGF receptor tyrosine kinases that play a role in tumor neoangiogenesis (the growth of new blood vessels). It also inhibits various oncogenic and tumor microenvironment kinases including, KIT, RET, PDGFR, and FGFR, which individually and collectively impact upon tumor growth, formation of a stromal microenvironment and disease progression.

Stivarga is a compound developed by Bayer and jointly promoted by Bayer and Onyx in the USA. In 2011, Bayer entered into an agreement with Onyx, under which Onyx receives a royalty on all global net sales of Stivarga in oncology.