ONTRUZANT (trastuzumab-dttb)是三星生物制药开发的第一个获FDA批准的肿瘤生物仿制药

近日，美国食品药品监督管理局（FDA）批准了Ontuzant（Trastuzumab DTTB），一种与Herceptin®I（Trastuzumab）相似的生物制剂，适用于所有符合条件的适应症，即Her2过度表达乳腺癌、转移性乳腺癌的辅助治疗。转移性胃癌或胃食管交界处腺癌患者谁没有接受过转移性疾病的治疗。

批准日期：2019年1月21日 公司：默克公司

ONTRUZANT（曲妥珠单抗 trastuzumab-dttb）注射，静脉注射用对照剂

美国初步批准：2019年

Ontuzant（trastuzumab dttb）与herceptin（trastuzumab）具有生物相似性。

警告：心肌病、输液反应、胚胎-胎儿毒性和肺毒性

完全警告性心肌病的完整处方信息：

曲妥珠单抗产品可导致亚临床和临床心衰，表现为CHF，并降低左室射血分数。

与蒽环类药物同时使用的风险最大。

治疗前和治疗中评估心脏功能。停药治疗心肌病。

输注反应，肺毒性：停止控制性有孔虫、血管水肿、间质性肺炎或急性呼吸窘迫综合征。

胚胎-胎儿毒性：怀孕期间接触曲妥珠单抗产品会导致羊水过少，在某些情况下会并发肺发育不良和新生儿死亡。告知患者这些风险

以及有效避孕的需要。

作用机理

The HER2（或c-erbb2）原癌基因编码185kDa的跨膜受体蛋白，其结构上与表皮生长因子受体有关。

Trastuzumab产品

在体外实验和动物实验中都显示，可以抑制过度表达HER2的人类肿瘤细胞的增殖。

曲妥珠单抗产品是抗体依赖性细胞毒性（ADCC）的介质。在体外，曲妥珠单抗介导的adcc被证明优先作用于HER2。

与不过度表达Her2的癌细胞相比，过度表达癌细胞。

适应症和使用

Ontuzant是一种her2/neu受体拮抗剂，用于：

HER2过度表达乳腺癌的治疗。

HER2高表达转移性胃器食管交界处腺癌的治疗。

根据FDA批准的曲妥珠单抗产品的伴随诊断选择患者进行治疗。

剂量和给药

仅用于静脉输液。不要以静脉推注的方式给药。

请勿将Ontuzant（Trastuzumab DTTB）替换为ADO Trastuzumab或用ADO Trastuzumab替换。

恩他辛

使用FDA批准的实验室试验进行HER2试验

熟练程度。

HER2过度表达乳腺癌的辅助治疗

管理地点：

初始剂量为4mg/kg，静脉滴注90分钟，然后每周30分钟静脉滴注2mg/kg，持续12周（紫杉醇或多西他赛）或18周（多西他赛和卡铂）。上一周后一周

对照剂剂量，每三周静脉输注6mg/kg，每次30-90分钟，共完成52周的治疗，或初始剂量8 mg/kg，每次90分钟静脉输注，然后30分钟静脉输注6 mg/kg。

每三周静脉输注90分钟，持续52周。

转移性Her2过度表达乳腺癌

初始剂量为4mg/kg（90分钟静脉注射），随后2mg/kg（30分钟静脉注射）。

转移性her2过表达胃癌

初始剂量为8mg/kg，静脉输注90分钟，随后每3周静脉输注30至90分钟，每次输注6mg/kg。

剂型及强度

注射用：150毫克冻干粉末，一剂一瓶，用于重组。

禁忌症

没有

警告和注意事项

化疗引起的中性粒细胞减少的恶化

不良反应

辅助性乳腺癌

最常见的不良反应（≥5%）是头痛、腹泻、恶心和寒战。

转移性乳腺癌

最常见的不良反应（≥10%）是发热、寒战、头痛、感染、充血性心力衰竭、失眠、咳嗽和皮疹。

转移性胃癌

最常见的不良反应（≥10%）是中性粒细胞减少、腹泻、疲劳、贫血、口炎、体重减轻、上呼吸道感染、发热、血小板减少、粘膜炎症、鼻咽炎和

味觉障碍。

要报告可疑的不良反应，请致电1-877-888-4231或FDAAT 1-800-FDA-1088或www.fda.gov/medwatch与默克公司（默克公司的子公司）联系。

在特定人群中使用

具有生殖潜能的雌雄动物：在开始控制前确认雌雄动物的妊娠状态。

患者咨询信息

*生物仿制品是指根据数据批准生物制品，证明其与FDA批准的生物制品（称为参考产品）高度相似，并且生物仿制品与参考产品之间没有临床意义的差异。

对照药物的生物相似性已在使用条件（例如适应症、给药方案）、强度、剂型和给药途径（如其全部处方信息中所述）下得到证明。

包装供应/储存和搬运

供应

注射用对照品（曲妥珠单抗DTTB）150mg/瓶，以白色单剂量瓶提供。

到淡黄色冻干无菌粉末，在真空下。每个纸箱包含一个单剂量瓶 NDC：

0006-5033-02。

保管部

在2°至8°C（36°至46°F）的温度下将Ontuzant小瓶储存在冰箱中，直到重新组装。

完整说明资料附件：https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761100s000lbl.pdf

FDA Approves Ontruzant(trastuzumab-dttb), a Biosimilar to Herceptin

U.S. Food and Drug Administration (FDA) has approved ONTRUZANT(trastuzumab-dttb), a biosimilar referencing HERCEPTIN(trastuzumab), across all eligible indications, namely adjuvant treatment of HER2-overexpressing breast cancer, metastatic breast cancer and metastatic gastric cancer or gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease. Please see Boxed Warnings and Important Safety Information for ONTRUZANT [®] below.

ONTRUZANT is Samsung Bioepis’ first oncology biosimilar to receive FDA approval, and will be marketed and distributed in the United States (US) by Merck, which is known as MSD outside of the US and Canada.

“For many cancer patients in the US, battling cancer has not only been a health issue, but a considerable financial burden brought on by cancer treatment. Biosimilars are intended to be lower cost, high-quality treatment options that have the potential to alleviate such burden. We sincerely hope our trastuzumab biosimilar will do exactly that,” said Sang-Jin Pak, Senior Vice President and Head of Commercial Division, Samsung Bioepis. “At Samsung Bioepis, we will continue to demonstrate our enduring commitment to biosimilars by further strengthening our pipeline and widening the availability of approved treatments for cancer patients across the US.”

About ONTRUZANT (trastuzumab-dttb) 

ONTRUZANT is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:

As part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel

With docetaxel and carboplatin

As a single agent following multi-modality anthracycline-based therapy

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product. 

* High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or. 

ONTRUZANT is indicated:

In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer

As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product. 

ONTRUZANT is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease. 

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product

Select Important Safety Information

Cardiomyopathy

ONTRUZANT administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection fraction with greatest risk when administered concurrently with anthracyclines. eva luate cardiac function prior to and during treatment. Discontinue ONTRUZANT for cardiomyopathy.

Infusion Reactions; Pulmonary Toxicity

Administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Discontinue ONTRUZANT for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Embryo-Fetal Toxicity

Exposure to ONTRUZANT during pregnancy can result in oligohydramnios in some cases complicated by pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception

Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab products in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not

Most Common Adverse Reactions

The most common adverse reactions for trastuzumab products in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia

The most common adverse reactions for trastuzumab products in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia

These are not all of the risks associated with ONTRUZANT . For additional information on ONTRUZANT indications, as well as Important Safety Information related to its use, including Boxed WARNINGS, please see the ONTRUZANT Prescribing Information HERE