Shanghai, China, Jan, 17^th, 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^[1]. SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases^[2]. The SCLC breaks down into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are in extensive stage when diagnosed^[3]. Their clinical condition deteriorates rapidly and the overall prognosis is poor. In the past 20 years, etoposide combined carboplatin/cisplatin was still the standards of care for ES-SCLC, but almost all patients in extensive stage relapse within one year^[4], 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.

References

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[2]Eskandar A, Ahmed A, Daughtey M, et al. Racial and sex differences in presentation and outcomes of small cell lung cancer in the United States: 1973 to 2010[J].Chest, 2015,147(4): e164-e165.

[3]Klautke G , Sauer R, Fietkau R .Combined Treatment Modality in Small Cell Lung Cancer[J]. Strahlentherapie Und Onkologie, 2008, 184(2):61-66.

[4]Puglisi M , Dolly S , Faria A , et al. Treatment options for small cell lung cancer – do we have more choice?[J].Br J Cancer, 2010, 102(4):629-638.