2023年1月17日，上海—复宏汉霖（2696.HK）宣布，公司自主研发的创新生物药抗PD-1单抗H药——汉斯状®（通用名：斯鲁利单抗注射液）新适应症上市申请获得国家药品监督管理局（NMPA）批准，联合卡铂和依托泊苷用于广泛期小细胞肺癌（ES-SCLC）的一线治疗，成为全球首个一线治疗小细胞肺癌的抗PD-1单抗，开启小细胞肺癌免疫治疗新时代。此前，H药已获批治疗微卫星高度不稳定 (MSI-H) 实体瘤和鳞状非小细胞肺癌（sqNSCLC）两项适应症。
H药此次获批主要基于一项随机、双盲、安慰剂对照的国际多中心III期临床研究（ASTRUM-005）。该研究在中国、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%为白人。此项研究结果在2022 ASCO年会上以口头报告形式首次公布，更新随访数据也于2022年12月ESMO Asia上发布。值得一提的是，2022年9月，ASTRUM-005研究结果于全球四大顶级医学期刊之一的《美国医学会杂志》（JAMA，影响因子：157.3）在线发表，成为全球首个登上JAMA主刊的小细胞肺癌免疫治疗临床研究，再度验证了国际学术界对该研究的高度认可。
ASTRUM-005研究分析显示，H药（斯鲁利单抗）联合化疗组的中位OS达15.8个月，较对照组显著延长4.7个月，OS得到了明显改善，H药（斯鲁利单抗）联合化疗组患者死亡风险降低38%（HR=0.62，95%CI: 0.50~0.76）。亚裔人群中位OS达15.9个月，较对照组延长4.8个月（HR=0.63，95%CI: 0.49~0.81）。其独立影像评估委员会根据RECIST v1.1评估的中位PFS也获得了延长（5.8 vs. 4.3个月；HR 0.47，95% CI: 0.38~0.58）。研究结果表明，H药联合卡铂-依托泊苷一线治疗既往未接受过治疗的广泛期小细胞肺癌（ES-SCLC）患者获益显著，达到预设的主要终点，且具有良好的安全性和耐受性，并有望为亚裔人群带来更显著的潜在获益。
Henlius’ Novel Anti-PD-1 mAb HANSIZHUANG (Serplulimab) Approved for the Treatment of ES-SCLC
World’s first anti-PD-1 mAb for the first-line treatment of SCLC
Making a new record with the median OS of 15.8 months in an international, multi-center, phase 3 clinical trial
Granted orphan drug designations by the FDA and the EC, paving the way for international commercialization
Shanghai, China, Jan, 17th, 2023 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that its first self-developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (generic name: serplulimab injection), in combination with carboplatin and etoposide for the first-line treatment of extensive stage small cell lung cancer (ES-SCLC), has been approved by the National Medical Products Administration (NMPA), making it the world’s first anti-PD-1 mAb for the first-line treatment of small cell lung cancer (SCLC). HANSIZHUANG had already been approved for the treatment of Microsatellite Instability-High (MSI-H) solid tumors and squamous non-small cell lung cancer (sqNSCLC).
Wenjie Zhang, Chairman, Executive Director, and CEO of Henlius, said, “This is the second approval HANSIZHUANG has received in the first-line treatment of lung cancer, after approval of sqNSCLC, demonstrating its great potential in lung cancer treatment. It is another milestone for HANSIZHUANG as well as a remarkable achievement for anti-PD-1 mAbs to improve survival notably in patients with SCLC. Looking forward, as the representative of China’s innovative drugs, HANSIZHUANG is expected to be approved in overseas markets to benefit more lung cancer patients with its consistent efficacy.”
Professor Ying Cheng, the leading principal investigator of the phase 3 clinical study of HANSIZHUANG on ES-SCLC, from Jilin Province Cancer Hospital, said, “SCLC is the most aggressive subtype of lung cancer, patients with SCLC deteriorate rapidly in clinical behavior and the overall prognosis is poor. The success of ASTRUM-005, a multi-center clinical trial of HANSIZHUANG, is a breakthrough in the treatment of ES-SCLC. Apart from providing a better immunotherapy option, this approval will also reshape the first-line treatment of ES-SCLC and promote the treatment of lung cancer around the world.”
Innovate to solve the dilemma of SCLC treatment
Lung cancer (LC) is one of the most common malignancies around the world. According to GLOBOCAN 2020, there were 2.2 million new LC cases and 1.8 million new deaths in 2020 worldwide, and LC is still the leading cause of cancer death. SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases. The SCLC breaks down into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are in extensive stage when diagnosed. Their clinical condition deteriorates rapidly and the overall prognosis is poor. In the past 20 years, etoposide combined carboplatin/cisplatin was still the standard of care for ES-SCLC, but almost all patients in extensive stage relapse within one year, with a median overall survival (OS) of only 10 to 11 months. The advent of immune checkpoint inhibitors has brought new hope to patients with ES-SCLC. At present, anti-PD-L1 mAbs combined with chemotherapy has prolonged the OS of patients with SCLC to 12-13 months compared to chemotherapy, but the improvements were still modest. Meanwhile, a number of anti-PD-1 mAbs have failed in SCLC, and more effective solutions are urgent needed.
The approval was primarily based on ASTRUM-005, a randomized, double-blind, placebo-controlled international multi-center phase 3 clinical study. The study has set up a total of 128 sites in various countries including China, Turkey, Poland, and Georgia, and enrolled 585 subjects who were screened from 114 sites, among whom 31.5% were White. The results of ASTRUM-005 were presented in oral for the first time at the 2022 ASCO annual meeting，and the results were updated at the 2022 European Society for Medical Oncology Asia (ESMO Asia) Congress in December 2022. In September 2022, the results of ASTRUM-005 had been published in The Journal of the American Medical Association (JAMA, impact factor of 157.3), one of the top four medical journals in the world, which made ASTRUM-005 the first study published on JAMA in SCLC immunotherapy, demonstrating the high level of academic acclaim on a global scale.
According to the study analysis, the median OS was significantly longer in the serplulimab group (15.8 months) than in the placebo group (11.1 months), and a 38% reduction in risk of death was observed in the serplulimab group compared with the placebo group(HR=0.62, 95%CI:0.50-0.76).The Asians subgroup also showed a 4.8 months longer median OS in the serplulimab group (HR=0.63，95%CI: 0.49-0.81). Median PFS assessed by the independent radiology review committee per RECIST v1.1 was prolonged with the addition of serplulimab (5.8 vs. 4.3 months; HR=0.47, 95%CI:0.38-0.58).The results indicated that HANSIZHUANG (serplulimab injection) in combination with chemotherapy (Carboplatin-Etoposide) could bring significant benefits against chemotherapy (Carboplatin-Etoposide) in the treatment of previously untreated patients with ES-SCLC, met the pre-defined primary endpoint criteria, and had good safety and tolerability. HANSIZHUANG could potentially bring more significant benefits to Asian patients.
Global footprint for more patients
HANSIZHUANG is the first innovative mAb developed by Henlius. Since launched in March 2022, HANSIZHUANG has become one of the pioneering anti-PD-1 mAb for the “pan-cancer” treatment of MSI-H solid tumors in China. Up to date, HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, sqNSCLC and ES-SCLC, its new drug application(NDA) in combination with chemotherapy for the first-line treatment of locally advanced/metastatic esophageal squamous cell carcinoma(ESCC) has also been accepted by the NMPA. As a backbone, HANSIZHUANG’s synergy with in-house products of the company and innovative therapies are forging ahead. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 12 clinical trials on immuno-oncology combination therapies in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc.
Guided by unmet clinical needs, Henlius has devoted itself to lung cancer and built a comprehensive layout of the first-line treatment for lung cancer in sqNSCLC, ES-SCLC, nsNSCLC and LS-SCLC, which covers more than 90% of lung cancer patients. In the field of SCLC, multi-regional clinical trials regarding ES-SCLC and LS-SCLC have been conducted and the results will support NDAs in overseas markets. In 2022, HANSIZHUANG was also granted orphan drug designations by the Food and Drug Administration(FDA) and European Commission(EC) for the treatment of SCLC. Based on the positive feedback of FDA Biologics license Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion results of the FDA's Class C consultation meeting, Henlius has initiated a bridging head-to-head trial in US patients with ES-SCLC to evaluate the efficacy of HANSIZHUANG, which propels the product towards US market approval further. According to the research progress in SCLC, the company plans to submit new drug applications of the product in the EU and US in the coming years.
In addition, Henlius actively promotes the commercialization of HANSIZHUANG to enhance its accessibility by marketing, channel management, pricing and market access. By the end of 2022, HANSIZHUANG has completed the tendering process on the procurement platform in 28 provinces in Chinese mainland and was included into the commercial medical insurance directory in 5 cities such as Ningbo, Jinhua, etc., benefiting more than 10,000 Chinese patients. As early as 2019, Henlius forged a partnership with PT Kalbe Genexine Biologics（KG Bio）to grant it an exclusive license to develop and commercialize HANSIZHUANG in relation to a monotherapy and two combination therapies in 10 Southeast Asian countries. To accelerate the launch of HANSIZHUANG in the United States, Henlius entered into an exclusive license agreement with Fosun Pharma for the commercialization of HANSIZHUANG in December 2022. By virtual of Fosun Pharma’s advantages and commercial capabilities, HANSIZHUANG will expand its overseas distribution fast to benefit more patients. Going forward, Henlius will continue to expand global commercialization layout of HANSIZHUANG to reach out to more countries and regions, which urges this product to step on to the world PD-1 stage and benefits a broader patient population worldwide with its world-class quality.
With HANSIZHUANG as a model, Henlius will further promote its innovative and differentiated product portfolio and expand the global footprint to establish a prestigious national brand and bring hope to more patients across the world.
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius and and the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 3 indications are approved for marketing in China, 1 NDA has been accepted by the NMPA, and more than 10 clinical trials are ongoing across the world.
HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC) . Its synergy with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 12 clinical trials on immuno-oncology combination therapies 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. As of now, the company has enrolled more than 3,100 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of White 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 first-line treatment for esophageal squamous cell carcinoma (ESCC) has been accepted by the NMPA. Furthermore, HANSIZHUANG was respectively recommended for the first-line treatment of ES-SCLC in the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) and the trentment of esophageal cancer (categary IA) in the 2022 China Guidelines for Radiotherapy of Esophageal Cancer. The associated clinical trial became the first study published in JAMA on SCLC immunotherapy. Serplulimab was also granted orphan drug designations by the FDA and EC for the treatment of SCLC, and the first patient has been dosed in a bridging head-to-head trial in the United States to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC.
Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 5 products have been launched in China, 1 approved for marketing in overseas markets, 18 indications approved worldwide, and 1 New Drug Application (NDA) accepted for review in China. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name in Europe: Zercepac®; trade names in Australia: Tuzucip® and Trastucip®, the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC) , making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Its NDA for the treatment of esophageal squamous cell carcinoma (ESCC) is under review. What's more, Henlius has conducted over 20 clinical studies for 15 products and 12 immuno-oncology combination therapies, expanding its presence in major markets as well as emerging markets.
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