复宏汉霖H药汉斯状一线治疗小细胞肺癌上市注册申请获受理

SCLC占肺癌总数的15%-20%，是肺癌中侵袭性最强的亚型，分为局限期小细胞肺癌（LS-SCLC）和广泛期小细胞肺癌（ES-SCLC），二者共同点是恶性程度高、转移早、疾病进展迅速，总体预后不良。目前抗PD-L1单抗联合化疗已陆续被最新版NCCN指南和CSCO指南推荐为ES-SCLC一线治疗方案，但近年来多款PD-1产品在ES-SCLC领域接连折戟，未使ES-SCLC患者真正获益。

此次受理主要是基于一项在既往未接受过治疗的ES-SCLC患者中比较H药注射液联合化疗（卡铂-依托泊苷）及安慰剂联合化疗（卡铂-依托泊苷）的临床有效性和安全性的随机、双盲、国际多中心、III期临床研究（ASTRUM-005）。该试验在中国、土耳其、欧盟波兰、格鲁吉亚等多个国家共开设128个试验中心，入组585例受试者，其中约31.5%为高加索人。2021年12月，公司宣布ASTRUM-005已于中期分析达到主要研究终点总生存期（OS），研究数据显示，H药联合化疗在总体人群和中国亚组均可延长OS，H药组总人群中位OS达到15.38个月，总人群降低死亡风险达38%（中国亚组达41%），显示出良好的疗效和安全性。充分的国际临床试验数据也有望支持H药在欧盟、美国等主流法规市场的申报，为全球临床应用奠定基础。

据GLOBOCAN数据显示，肺癌是全球发病率第二大高发癌种，2020年全球肺癌新发病例220万例，新发肺癌死亡病例180万例，我国约有超过81万新发肺癌病例，位居癌症死亡人数第一位。非小细胞肺癌约占所有肺癌的85%，其中鳞状非小细胞肺癌约有30%，多数肺癌患者确诊时已处于疾病晚期，缺乏手术治疗机会。免疫检查点抑制剂的出现为临床提供了新的治疗选择。

公司聚焦肺癌一线治疗进行了全面布局，围绕鳞状非小细胞肺癌（sqNSCLC）、非鳞状非小细胞肺癌（nsNSCLC）、ES-SCLC、LS-SCLC等适应症进行广泛的PD-1免疫治疗探索。在非小细胞肺癌领域，H药联合化疗在既往未接受治疗的局部晚期或转移性sqNSCLC患者中开展一项随机、双盲、国际多中心III期临床试验，目前上市注册申请已获得NMPA受理。此外，另一项H药联合汉贝泰^®一线治疗转移性nsNSCLC患者的III期临床研究亦在中国完成首例患者给药。在SCLC领域，针对ES-SCLC开展国际多中心III期临床研究（ASTRUM-005）之外，公司亦于近期获得国家药品监督管理局管理局（NMPA）批准针对LS-SCLC开展国际多中心III期临床研究。H药用于治疗SCLC于近期获得FDA授予的孤儿药资格认定（Orphan-drug Designation），有助于H药在美国的后续研发、注册及商业化等方面享受一定的政策支持。

未来公司也将继续以患者需求为核心，积极推进H药的免疫联合疗法和产品的更多国际临床注册，为全球更多患者带去福音。

The NDA of Henlius Novel Anti-PD-1 mAb Serplulimab for the First-Line Treatment of Small Cell Lung Cancer Accepted by NMPA

Shanghai, China, April 11^th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the New Drug Application (NDA) of HANSIZHUANG (serplulimab), a novel anti-PD-1 monoclonal antibody (mAb) independently developed by the company, in combination with chemotherapy for the first-line treatment of extensive stage small cell lung cancer (ES-SCLC) has been accepted by the National Medical Products Administration (NMPA). Henlius also plans to file MAA in the EU in 2022. There’s no PD-1 has been approved globally for first-line treatment of SCLC up to date and HANSIZHUANG potentially the world’s first PD-1 inhibitor for the first-line treatment of SCLC.

Professor Ying Cheng, the principal investigator of the study, Director of Jilin Department of Medical Oncology Cancer Center, Jilin Province Lung Cancer Diagnosis and Treatment Center, and Jilin Cancer Hospital Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center, said, "ASTRUM-005 is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. The favorable clinical results demonstrated that the predefined primary study endpoint had been reached, providing evidence of safety and efficacy. We are hoping that the approval of HANSIZHUANG for the treatment of ES-SCLC comes soon to mend the gap and bring a new treatment option to patients living with ES-SCLC. "

Mr. Jason Zhu, President of Henlius, said, "HANSIZHUANG is an innovative mAb independently developed by Henlius, and SCLC is the third indication for which the NDA has been accepted by NMPA and Orphan-Drug Designation has been recently granted by the United States Food and Drug Administration (FDA). Based on the large number of unmet clinical needs as well as the intractable cancers both globally and in China, the company has implemented a comprehensive first-line treatment strategy for lung cancer with multiple multi-center Phase 3 clinical trials. Going forward, we will proactively promote the combination immunotherapy of HANSIZHUANG and clinical research, thereby benefiting more patients in China and around the world."

HANSIZHUANG significantly improves the overall survival and fill the gap in demand for patients with SCLC

Small cell lung cancer (SCLC) accounts for 15%–20% of all cases and is the most aggressive type of lung cancer (LC). It is classified into two stages: limited stage (LS-SCLC) and ES-SCLC, with both exhibiting high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. At present, anti-PD-L1 mAb combined with chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for ES-SCLC. In recent years, however, a number of PD-1 mAbs have failed in the area.

The NDA is based on the results from a randomised, double-blind, international, multi-centre, phase 3 clinical study (ASTRUM-005) that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy (carboplatin-etoposide) in previously untreated patients with ES-SCLC. This study has set up about 128 sites in China, Turkey, Poland, Georgia, etc. and 585 subjects were enrolled, among whom 31.5% were Caucasian. In December 2021, ASTRUM-005 had met its primary study endpoint of the overall survival (OS) in the interim analysis results. The study results demonstrated that HANSIZHUANG can significantly extend the OS to 15.38 months for the group of HANSIZHUANG, reducing risk of death by 38% (41% in the Asian subgroup) a manageable safety profile. The global clinical data lays a solid foundation for future applications across the world.

China has the highest incidence of LC, and HANSIZHUANG is intended as a first-line treatment option for all subtypes of LC

According to GLOBOCAN 2020, LC is the second most common cancer around the world. There were 2.2 million new LC cases worldwide, with China accounting for 0.8 million new LC cases. Moreover, with 1.8 million new deaths in 2020, LC is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% among LC, with squamous non-small cell lung cancer (sqNSCLC) accounting for about 30%. Most lung cancer patients are diagnosed at an advanced stage and lack the opportunity for surgical resection. The advent of immune checkpoint inhibitors has been proved to bring hope to patients with LC.

Henlius has carried out a comprehensive first-line immune-oncology treatment layout for LC in sqNSCLC, non-squamous non-small cell lung cancer (nsNSCLC), ES-SCLC, and LS-SCLC. For NSCLC, the company has conducted a randomised, double-blind, global multi-centre Phase 3 clinical trial in patients with locally advanced or metastatic sqNSCLC patients to compare HANSIZHUANG in combination with chemotherapy versus chemotherapy in respect of efficacy and safety. The NDA was accepted as a result of the study meeting the primary endpoints. Also, a study to explore dual mAbs combination therapy of HANSIZHUANG and HANBEITAI (bevacizumab) for the first-line treatment of nsNSCLC has entered the pivotal Phase 3 stage. For SCLC, on the other hand, the investigational new drug application (IND) of international multicenter phase 3 studies of HANSIZHUANG in patients with LS-SCLC has been approved by NMPA in addition to ASTRUM-005 for the treatment of ES-SCLC. Notably, FDA has granted Orphan-Drug Designation for HANSIZHUANG for the treatment of SCLC, benefiting the continuous development of HANSIZHUANG and the enjoyment of certain policy support in terms of registration and commercialization in the United States.

In the future, the company will continue to emphasize unmet clinical needs and actively promote the combination immunotherapy of HANSIZHUANG and international regulatory registration to benefit more patients around the world.

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. It is approved by the NMPA for the treatment of MSI-H solid tumors in March 2022. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies of HANSIZHUANG worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDA of the treatment for squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. Furthermore, the global multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy in previously untreated extensive small-cell lung cancer (ES-SCLC) met the primary endpoint of overall survival (OS) with remarkable readouts. Its NDA in China has been accepted by the NMPA and MAA in the EU are expected to be filed in 2022, making this product potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.