福斯特城（美国加州）和上海（中国）-2019 年9月9 日。盟科医药今天宣布，在美国开展的一项代号为MRX4-201的随机、双盲、与利奈唑胺对照，评价康泰唑胺磷酸盐（contezolid acefosamil ，MRX-4）治疗急性细菌性皮肤及皮肤组织感染（ABSSSI）的二期临床试验获得积极结果。康泰唑胺磷酸盐达到了所有首要和次要的疗效终点，并显示了更好的血液学安全性。
“我们衷心感谢参与此项二期临床研究的患者、研究者和工作人员”，盟科医药的总裁和CEO 袁征宇博士说，“我们非常高兴看到这项研究取得了出色的结果，我们计划在明年将康泰唑胺磷酸盐推进至三期临床试验。”袁博士补充道。
此项二期临床试验在美国7个研究中心开展，入组了196例ABSSSI 患者，以利奈唑胺为对照，按2:1的比例分组（康泰唑胺磷酸盐 131 例，利奈唑胺65 例），评价注射和口服康泰唑胺磷酸盐进行10-14天治疗的安全性和有效性。康泰唑胺磷酸盐组受试者接受了注射1500mg 的初始剂量，随后改为一天两次注射1000mg，并在至少三次注射给药后，可选择转为一天两次口服1300mg 的序贯治疗，而利奈唑胺组受试者则接受一天两次注射600mg 的剂量，在至少三次注射给药后，可选择转为一天两次口服600mg的序贯治疗。
研究的首要疗效终点是在意向治疗人群（ITT）进行早期评价（EA）访视（开始药物治疗后的48-72小时内）时的早期临床反应率，康泰唑胺磷酸盐组为77.9%，而利奈唑胺组为78.5%。ITT 人群在治疗后评价（PTE）访视（治疗结束[EOT]后7-14 天）的反应率同样相似，康泰唑胺磷酸盐组为76.3%，而利奈唑胺组为73.8%。在EA、EOT 和PTE 访视时临床可评价和微生物评价人群的次要疗效终点，在两组中同样相似。鉴别发现最常见的致病菌是耐甲氧西林金黄色葡萄球菌（MRSA），两组中MRSA 感染患者的疗效也同样相当。
两组中治疗后出现的不良事件（TEAEs）的总体发生率相当，包括与药物相关的TEAEs（ 康泰唑胺磷酸盐组为16.3%，利奈唑胺组为14.1%）。恶心和呕吐是最为常见的TEAEs，大多为轻度或中度。试验中无严重的药物相关TEAEs，或因研究药物导致提前退出。总体上，实验室检查结果相似，但中性粒细胞和血小板计数低于正常值下限（LLN）或者显著异常（SA）的患者比例，在康泰唑胺磷酸盐组要低于利奈唑胺组（中性粒细胞：康泰唑胺磷酸盐低于LN为3.7%，SA为0%，而利奈唑胺组低于LLN 为7.4%，SA 为3.7%；血小板：康泰唑胺磷酸盐组低于LLN 为7.6%，SA 为2.5%，而利奈唑胺组低于LLN为12.1%，SA为5.2%）。
“康泰唑胺磷酸盐的注射和口服剂型，达到了FDA和EMA 细菌皮肤感染临床试验指导原则中的疗效终点，因此在治疗ABSSSI 包括MRSA 感染中是有效的，并且这一治疗方案安全，耐受性良好，”临床开发高级副总裁，Edward Fang 医学博士说道。“本临床试验的结果支持开展针对ABSSSI 和糖尿病足感染（DFI）的关键三期临床试验，而且在和利奈唑胺的对比中，康泰唑胺磷酸盐显示了更低的血液学检查异常，说明具有比其他噁唑烷酮类抗生素潜在的安全性优势，这在通常需要治疗超过14天的DFI 患者中具有重要的意义” Fang 博士补充道。利奈唑胺是“重磅炸弹”级的抗生素，用于治疗多重耐药革兰氏阳性菌感染，包括MRSA 和万古霉素耐药肠球菌（VRE）感染，但是其众所周知的血液学毒性经常限制了临床上的应用。盟科医药计划开展针对ABSSSI和DFI 的三期临床试验，以进一步确认包括在更长治疗周期情况下康泰唑胺磷酸盐的安全性和有效性。
关于盟科医药
盟科（http://www.micurxchina.com）是一家临床阶段的生物技术公司，专注于发现、开发和商业化治疗多重耐药（MDR）“超级细菌”感染的抗菌药物。自2007年成立以来，凭借管理团队在抗菌新药研发领域的丰富经验，和中美两地的科研团队，盟科已经建立了包括康泰唑胺（MRX-I）、康泰唑胺磷酸盐(MRX-4)、MRX-8 （新型针对MDR 革兰氏阴性菌的多粘菌素类药物）和MRX-12（针对MDR 革兰氏阴性菌的新类型药物）的研发管线。我们的使命是抗击WHO 发布的“超级细菌”清单上的病原菌。我们的首个产品，康泰唑胺（MRX-I）是下一代治疗金黄色葡萄球菌（MRSA）的噁唑烷酮类抗生素，旨在通过结构改进减少这类抗生素所造成的血液不良反应。2015 年，盟科在美国和中国分别成功完成了MRX-I 的两项独立二期研究，并在2019 年，在中国完成了复杂性皮肤和软组织感染(cSSTI)的3期研究。康泰唑胺磷酸盐（MRX-4）是康泰唑胺的前药，其口服和注射剂型将启动针对多重耐药革兰氏阳性菌的全球开发。康泰唑胺和康泰唑胺磷酸盐均已获得了美国FDA 授予的QIDP 和快速审评认定。公司在美国加州旧金山市郊和中国上海设有研发实验室。公司已经通过领先的风投资本公司，包括晨兴创投（Morningside Ventures）、百奥财富（BVCF）、金浦健康基金（GPHealthcare Capital）、金浦互联基金（GP TMT Capital）、本草资本（3EBioventures Capital）和德联资本（Delian Capital）募集了总计1.07 亿美元的资金。详情请访问：www.micurxchina.com。
联系人
李峙乐(Jerry)
高级副总和首席财务官
盟科医药有限公司.
电话: +852 6185 7868 (HK)
zli@micurx.com
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英文版通讯文章见下文
MicuRx Pharmaceuticals Reports PositiveTop-Line Results from a US Phase 2 ABSSSI Clinical Trial of Novel AntibioticContezolid Acefosamil
FOSTER CITY, California, and SHANGHAI,China - September 9, 2019. MicuRx Pharmaceuticals, Inc., today announcedpositive top-line results for study MRX4-201, a US Phase 2 randomized,double-blind clinical trial comparing contezolid acefosamil (MRX-4) with linezolidfor the treatment of acute bacterial skin and skin structure infections(ABSSSI). Contezolid acefosamil met all primary and secondary efficacyendpoints with a potentially improved hematologic safety profile.
“We sincerely appreciate theparticipation of the patients and the investigators and their study staff inthis Phase 2 clinical trial,” said Dr. Zhengyu Yuan, President and CEO ofMicuRx. “We are very pleased with the excellent results of this study and planto advance contezolid acefosamil into Phase 3 development next year,” continuedDr. Yuan.
The Phase 2 trial enrolled 196 ABSSSIpatients in a 2:1 ratio (contezolid acefosamil 131 subjects, linezolid 65subjects) at 7 centers in the United States to evaluate the safety and efficacyof the intravenous (IV) and oral formulations of contezolid acefosamil for10-14 days of therapy compared to linezolid. Contezolid acefosamil subjectsstarted with a loading dose of 1500 mg IV followed by twice daily 1000 mg IVdoses with the option after at least 3 IV doses to switch to 1300 mg oral dosestwice daily; linezolid subjects started with 600 mg IV twice daily for at least3 doses, after which they could switch to oral 600 mg twice daily.
For the primary efficacy endpoint, thepercentages of subjects in the intent-to-treat (ITT) population with favorableearly clinical responses at the early assessment (EA) visit (48-72 hours afterthe start of study drug) were 77.9% in the contezolid acefosamil group and78.5% in the linezolid group. Outcomes were also similar in the ITT populationat the post-therapy evaluation (PTE) visit (7-14 days after end of therapy[EOT]), with favorable responses of 76.3% in the contezolid acefosamil groupand 73.8% in the linezolid group. Similar results between the study groups wereobserved in other secondary efficacy outcomes in clinically evaluable and microbiologicalpopulations at the EA, EOT, and PTE visits. Methicillin-resistantStaphylococcus aureus (MRSA) was the most commonly identified pathogen, andefficacy outcomes were similar in subjects between the two study arms with MRSAinfections.
The overall incidence oftreatment-emergent adverse events (TEAEs) was similar between the study arms,including TEAEs considered to be related to study drug (contezolid acefosamil 16.3%,linezolid 14.1%). Nausea and vomiting were the most common TEAEs, and most weremild or moderate in severity. There were no drug-related TEAEs considered to beserious or that led to discontinuation of study drug. Overall, safetylaboratory changes were similar, though the proportions of subjects withneutrophil and platelet values that were below the lower limit of normal (LLN)or substantially abnormal (SA) were lower in the contezolid acefosamil groupthan in the linezolid group (neutrophils: contezolid acefosamil below LLN 3.7%and SA 0%, linezolid below LLN 7.4% and SA 3.7%; platelets: contezolidacefosamil below LLN 7.6% and SA 2.5%, linezolid below LLN 12.1% and SA 5.2%).
“The IV and oral formulations ofcontezolid acefosamil appear to be effective in treating ABSSSI, including MRSAinfections, as evaluated by endpoints consistent with FDA and EMA bacterialskin infection clinical trial guidance documents, with a dosing regimen thatwas safe and well-tolerated,” said Edward Fang, MD, Senior Vice President,Clinical Development. “The Phase 2 data support proceeding to pivotal Phase 3ABSSSI and diabetic foot infection (DFI) studies, and the lower frequencies ofhematologic laboratory abnormalities observed with contezolid acefosamilcompared with linezolid suggest a potential improvement in safety over otheroxazolidinones that may prove even more significant in patients with DFI whooften require treatment beyond 14 days,” added Dr. Fang. Linezolid became a“blockbuster” antibiotic for the treatment of multidrug-resistant (MDR)Gram-positive infections, including MRSA and vancomycin-resistant enterococci(VRE) infections, despite well-known hematologic toxicity which often limitsclinical utility. MicuRx plans Phase 3 clinical trials in ABSSSI and DFI inorder to confirm the safety and efficacy profile of contezolid acefosamil,including with longer duration therapy.
About MicuRx Pharmaceuticals, Inc.
MicuRx Pharmaceuticals(http://www.micurx.com/) is a clinical-stage biopharmaceutical company focusedon the discovery, development, and commercialization of antimicrobial therapeuticsfor multidrug-resistant (“MDR”) “superbug” infections. Since our inception in2007, we have leveraged our management team’s extensive experience in thediscovery and development of novel antimicrobial agents, and our scientists inthe US and China have built a pipeline that includes contezolid (MRX-I),contezolid acefosamil (MRX-4), MRX-8 (novel polymyxin MDR Gram-negative agent),and MRX-12 (new class MDR Gram-negative agent). Our mission is to combatpathogens on the WHO list of “superbugs”. Our lead compound, contezolid(MRX-I), a next-generation oxazolidinone targeting methicillin-resistant Staphylococcusaureus (MRSA), was structure-designed to reduce the hematologic toxicity and monoamineoxidase inhibition risk of this antibiotic class. In 2015, MicuRx completed twoindependent Phase 2 studies in the US and China for oral contezolid, and in2019, completed a Phase 3 study in China for the treatment of complicated skinand soft tissue infections (cSSTI). Contezolid acefosamil (MRX-4) is a prodrugof contezolid and is planned for global development in battling MDRGram-positive infections with both oral and IV formulations. Both contezolidand contezolid acefosamil have been granted QIDP designation and Fast Trackstatus by the US FDA. MicuRx has R&D centers outside of San Francisco,California, and in Shanghai, China. The company has raised a total of US$107million through leading venture capital firms including Morningside Ventures,BVCF, GP Healthcare Capital, GP TMT Capital, 3E Bioventures Capital, and DelianCapital. Visit www.micurx.com for more information.
Contact
Zhiyue (Jerry) Li
Senior Vice President and ChiefFinancial Officer
MicuRx Pharmaceuticals, Inc.
Phone: +852 6185 7868 (HK)
zli@micurx.com
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