The China NMPA Approved CYRAMZA® (ramucirumab) for the Treatment in Patients with Hepatocellular Carcinoma

ROCKVILLE, Md. and SUZHOU, China, Oct. 10, 2022 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune, ophthalmology and other major diseases, is pleased to see that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for CYRAMZA® (ramucirumab) in patients with hepatocellular carcinoma (HCC, also known as liver cancer), who have an alpha fetoprotein of ≥400 ng/mL and have been treated with sorafenib. In March 2022, CYRAMZA (ramucirumab) was approved by the NMPA in combination with paclitaxel for second-line treatment in patients with advanced or metastatic, gastric or gastro-esophageal junction (GEJ) adenocarcinoma, making it the first and only targeted drug approved for the second-line treatment of advanced or metastatic, gastric or gastro-esophageal junction (GEJ) adenocarcinoma in China.

CYRAMZA (ramucirumab) has been discovered and developed by Lilly. In March 2022, Innovent and Lilly expanded their strategic partnership in oncology, which includes an agreement for Innovent to obtain the sole commercialization rights of CYRAMZA (ramucirumab) once approved in China, which positions Innovent to be fully responsible for the pricing, importation, marketing, distribution and detailing of this product. With this further expanded oncology product portfolio, Innovent intends to use its experienced oncology commercial team to leverage its broad commercial coverage in hospitals and pharmacies at various tiers and to provide integrated patient solutions with strong synergies to cancer patients in China.

This new approval was based on the results of the REACH-2 study[1],[2], a global randomized, double-blind, placebo-controlled Phase 3 clinical trial. The REACH-2 study is the first Phase 3 clinical trial in HCC to obtain positive results in a biomarker-enriched population known for poor prognosis. On the primary endpoint of overall survival (OS), treatment with CYRAMZA significantly improved the OS of patients compared to placebo (HR: 0.71; 95% CI: 0.53-0.95; P=0.020). The median OS was 8.5 months with CYRAMZA, compared to 7.3 months with placebo. On the secondary endpoint of progression-free survival (PFS), median PFS was significantly improved with CYRAMZA (2.8 months vs. 1.6 months for placebo (HR: 0.45; 95% CI: 0.34-0.60; P<0.0001)). Objective response rate (ORR) was numerically higher with CYRAMZA compared to placebo (4.6% vs. 1.1%). Disease control rate (DCR) was higher with CYRAMZA than with placebo (59.9% vs. 38.9%). CYRAMZA was well-tolerated in Chinese patients and the overall patient population. The safety and efficacy profile of CYRAMZA in the Chinese population was consistent with that observed in previously reported global studies[2].

Professor Shukui Qin, the principal investigator of REACH-2 in China and the Director of the Cancer Center of Nanjing Jinling Hospital stated, "Primary Liver Cancer (PLC) is the fourth most common cancer in terms of prevalence and the second leading cause of cancer-related mortality in China with only a 12.1% five-year survival rate. HCC is the main type of PLC and most HCC patients with AFP ≥ 400ng/ml experience greater disease progression on or after first-line treatment[3]. New treatment options are urgently needed to improve outcomes in these patients[4]. Globally, CYRAMZA is the first approved novel medicine specifically evaluated in the biomarker-enriched population of HCC patients with AFP ≥ 400ng/ml; the study results in Chinese patients demonstrated a consistent efficacy and safety profile with the global population. I believe the approval will ignite a positive impact on the clinical practice of liver cancer in China, bringing a new and efficacious treatment option for Chinese patients with advanced HCC."

Dr. Yongjun Liu, President of Innovent, stated, "Hepatocellular carcinoma ranks fifth among the number of new cases in China, with approximately 410,000 new cases yearly and the number of deaths each year are nearly the same[3]. Most patients will experience disease progression after current first-line therapy and are left with limited treatment options. We are excited about the approval of CYRAMZA, the first innovative drug proven to have clinical benefits for a biomarker-enriched population of patients with HCC. This differentiated product will potentially be an exciting treatment option and bring new hope to patients in China with advanced HCC. The successive approvals of CYRAMZA in second-line GC/GEJ and HCC this year enable us to provide integrated patient solutions with strong portfolio synergies while enhancing our leading franchise in these two large cancer indications. Innovent is fully committed to making these new treatment options available to benefit more cancer patients in China as soon as possible."

About Hepatocellular Carcinoma

Primary liver cancer(PLC)is a common malignancy of the digestive system worldwide, among which about half of all new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), which accounts for 85 to 90 percent, and a small number of cases of intrahepatic cholangiocarcinoma(ICC)and HCC-ICC mixed liver cancer. In China, HCC is primarily caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.[5]

About CYRAMZA® (ramucirumab)

CYRAMZA® is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that binds specifically to VEGFR-2, thereby blocking the binding of the receptor ligands (VEGF-A, VEGF-C, and VEGF-D) – which may slow tumor growth.[6] In recent years, studies have shown that the VEGF pathway is an important signaling pathway involved in tumor angiogenesis, and it is also the main target pathway in targeted therapy of liver cancer[7]. From the existing research results, the single drug use of compounds targeting the VEGF pathway can bring survival benefits to patients and is a very promising treatment method in the treatment of liver cancer.[7]

In March 2022, CYRAMZA® (ramucirumab) in combination with paclitaxel was approved by the National Medical Products Administration (NMPA) for second-line treatment in patients with advanced or metastatic, gastric or gastro-esophageal junction (GEJ) adenocarcinoma.

In October 2022, CYRAMZA® (ramucirumab) was approved by the NMPA for patients with Hepatocellular Carcinoma (HCC) who have an alpha fetoprotein (AFP) of ≥400 ng/mL and have been treated with sorafenib.

About Innovent's Strategic Cooperation with Eli Lilly and Company

Innovent entered into a strategic collaboration with Lilly focused on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Innovent and Lilly will co-develop and commercialize oncology medicines, including TYVYT® (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered into a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. This collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August 2020,Lilly and Innovent announced a global expansion of their strategic alliance for sintilimab, whereby Lilly obtained an exclusive license for sintilimab for geographies outside of China and plans to pursue registration of sintilimab in the U.S. and other geographies outside of China. In March 2022, Lilly and Innovent entered into a fifth agreement to expand their strategic partnership in oncology, in which Innovent obtained the sole commercialization rights to import, market, promote, distribute and detail CYRAMZA® (ramucirumab) and selpercatinib once approved in Mainland China, and a right of first negotiation for potential future commercialization of pirtobrutinib in Mainland China.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 34 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 8 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection), Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR ABL TKI), CYRAMZA® (ramucirumab) and selpercatinib, 2 assets under NMPA NDA review, 4 assets in Phase 3 or pivotal clinical trials, and an additional 20 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

TYVYT® (sintilimab injection) is not an approved product in the United States.

BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab biosimilar injection, Innovent)

HALPRYZA® (rituximab biosimilar injection, Innovent)

SULINNO® (adalimumab biosimilar injection, Innovent)

Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

CYRAMZA® (ramucirumab, Lilly). CYRAMZA® was discovered and developed by Lilly and licensed to Innovent for commercialization in Mainland China.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

Reference

[1] Zhu A X, Kang Y K, Yen C J, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. The Lancet Oncology, 2019, 20(2): 282-296.

[2] Qin S, Shao G, Bai Y, et al. Chinese population analysis in REACH-2: A phase III trial of ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma and elevated baseline alpha-fetoprotein following first-line sorafenib. 2021 Chinese Society of Clinical Oncology (CSCO) annual meeting.

[3] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: a cancer journal for clinicians, 2021, 71(3): 209-249.

[4] Tangkijvanich P et al. J Clin Gastroenterol 2000, 31(4):302-8

[5] National Health Commission of the PRC 《Guidelines for the Treatment of Primary Liver Cancer (2022 Edition)》

[6] Lu D, et al. Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem. 2003; 278: 43496–43507.

[7] Clarke JM, et al. Targeted inhibition of VEGF receptor 2: an update on ramucirumab. Expert Opin Biol Ther. 2013; 13: 1187–1196.