Innovent Announces NMPA Approval of CYRAMZA® (Ramucirumab) for Second-Line Treatment of Advanced Hepatocellular Carcinoma in China

Rockville, U.S. and Suzhou, ChinaOctober 10, 2022PR Newswire -- Innovent Bio (HKEX: 01801), a biopharmaceutical company dedicated to the research, development, production, and commercialization of innovative drugs in major disease areas such as oncology, autoimmune diseases, metabolic disorders, and ophthalmology, is pleased to see the anti-angiogenic drug Xiranzo.^®(Ramucirumab) has been approved by the National Medical Products Administration (NMPA) for the treatment of hepatocellular carcinoma (HCC) patients who have previously received sorafenib treatment and have alpha-fetoprotein (AFP) ≥400 ng/mL. Cyramza^®(Ramucirumab) has previously been approved in mainland China for use in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma who have experienced disease progression during or after fluoropyrimidine- or platinum-containing chemotherapy. It is the first and only targeted drug approved in China for second-line treatment of advanced gastric cancer.

Cyramza^®(Ramucirumab) was developed by Eli Lilly and Company. In March 2022, Innovent Bio further deepened its strategic cooperation with Eli Lilly and Company in the field of oncology, which includes Innovent Bio obtaining Cyramza from Eli Lilly.^®(Ramucirumab) exclusive commercial rights in China, fully responsible for Cyramza^®The pricing, import, marketing, distribution, and sales promotion of (Ramucirumab). Innovent Bio will leverage its extensive product pipeline in major cancer indications, a mature and comprehensive oncology commercialization platform, and broad commercial coverage across hospitals and pharmacies nationwide in China, aiming to provide Chinese cancer patients with an integrated solution that offers strong combination synergies.

The approval of this new indication is based on the results of the REACH-2 study.^[1]，[2]The REACH-2 study is a global, randomized, double-blind, placebo-controlled Phase III study.The FirstIn the field of hepatocellular carcinoma, studies using biomarkers to enrich populations and obtain positive results have shown in the primary cohort thatLeiThe median overall survival (OS) in the Moexilumab group was 8.5 months, significantly longer than that in the placebo group (7.3 months, HR: 0.71, 95% CI: 0.53-0.95, P=0.020). The median progression-free survival (PFS) in the Ramucirumab group was 2.8 months, markedly better than the 1.6 months in the placebo group (HR: 0.45, 95% CI: 0.34-0.60, P<0.0001). The objective response rate (ORR) was 4.6% vs 1.1%, and the disease control rate (DCR) was 59.9% vs 38.9%. The treatment was well tolerated. In the overall Chinese patient population (including all Chinese patients in both the main cohort and the extended cohort), the treatment was generally well tolerated with no new safety signals observed. Its efficacy and safety were consistent with the global data.^[2]。

REACH-2Principal Investigator in China, Professor Shukui Qin, Cancer Center of Nanjing Jinling Hospital"In China, primary liver cancer is the fourth most common malignant tumor and the second leading cause of cancer-related deaths. The disease burden of liver cancer is heavy, with a 5-year survival rate of only 12.1%. There are still unmet clinical needs in the treatment of advanced liver cancer."^[3]Patients with baseline AFP ≥400 ng/ml have an overall poorer prognosis, and there is an urgent need for new effective and well-tolerated treatment options.^[4]Ramucirumab isThe World's FirstThe drug, which was approved for second-line treatment of hepatocellular carcinoma based on biomarker-enriched populations, also demonstrated efficacy and safety consistent with global results in the Chinese population. This has more guiding significance for clinical practice in Chinese liver cancer patients, and it is believed that it will provide new and effective treatment options for Chinese patients with advanced hepatocellular carcinoma in the future.

Dr. Yongjun Liu, President of Innovent BioLiver cancer is the fourth most common cancer in China, with approximately 410,000 new cases each year and nearly as many deaths as new cases annually.^[3]，Most patients will experience disease progression after existing first-line treatments, and the treatment situation remains severe. Cyramza^®(Ramucirumab) As the first drug to demonstrate clinical benefit in a biomarker-selected population with hepatocellular carcinoma, we look forward to its recent approval as a new option for second-line treatment of advanced hepatocellular carcinoma, bringing new hope to patients with hepatocellular carcinoma. Meanwhile, Cyramza^®(Ramucirumab) has been successively approved for two indications—gastric cancer (or gastroesophageal junction adenocarcinoma) and liver cancer—which will further enhance Innovent Bio's leading advantage and product synergy value in the field of major cancer treatments. Innovent Bio will, as always, adhere to its original mission of developing high-quality biologics that are affordable for the general public, continuously promoting the early achievement of the 'Healthy China 2030' goals, and benefiting more cancer patients in China.

About Liver Cancer

Liver cancer is a common malignant tumor of the digestive system worldwide, and the number of liver cancer patients in China accounts for about half of the global total.^[3]Liver cancer seriously threatens the lives and health of people in China. The main pathological type of liver cancer is hepatocellular carcinoma (HCC), accounting for 85% to 90%; a small number are intrahepatic cholangiocarcinoma (ICC) and mixed-type HCC-ICC, among others. In China, HCC is mainly caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.^[5]。

About Ramucirumab

Ramucirumab is a fully human IgG1 monoclonal antibody that specifically binds to VEGFR-2, efficiently blocking the binding of VEGF-A to VEGFR-2, and also inhibiting the binding of VEGF-C and VEGF-D to VEGFR-2.^[6]In recent years, studies have shown that the anti-vascular endothelial growth factor (VEGF) pathway is an important signaling pathway involved in tumor angiogenesis and is also the main targeted pathway in liver cancer targeted therapy.^[7]Based on existing research findings, drugs that target the VEGF pathway used as monotherapy can provide survival benefits to patients and represent a highly promising treatment approach in liver cancer therapy.

In March 2022, Ramucirumab was approved in China in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma who experienced disease progression during or after fluoropyrimidine- or platinum-containing chemotherapy. It became the first and only targeted drug approved in China for second-line treatment of advanced gastric cancer. In October 2022, Ramucirumab was approved in China for the treatment of hepatocellular carcinoma (HCC) patients who had previously received sorafenib treatment and had alpha-fetoprotein (AFP) ≥400 ng/mL.

About the Strategic Cooperation between Innovent Bio and Eli Lilly and Company

Innovent Bio and Eli Lilly and Company reached a biotechnology drug development collaboration in March 2015, which is also one of the largest collaborations between a Chinese biopharmaceutical company and a multinational pharmaceutical company to date. According to the terms of the collaboration, Innovent Bio and Eli Lilly will jointly develop and commercialize oncology drugs in China, including Tyvyt® (Sintilimab Injection). In October 2015, the two parties announced a further expansion of their established drug development collaboration, adding three novel antibody therapies for cancer treatment. In August 2019, the collaboration expanded into the diabetes field, with Innovent Bio gaining authorization to develop and commercialize one of Eli Lilly's potential global best-in-class clinical-stage diabetes drugs in China. These three collaborations with Eli Lilly and Company signify that Innovent Bio has established a comprehensive strategic partnership between a Chinese innovative pharmaceutical company and a global pharmaceutical giant, covering new drug research and development, clinical studies, production quality, and marketing sales. In August 2020, Innovent Bio and Eli Lilly and Company announced the expansion of their strategic collaboration on Sintilimab. Innovent Bio will grant Eli Lilly exclusive rights to Sintilimab outside of China, and Eli Lilly will be committed to bringing Sintilimab to North America, Europe, and other regions. In March 2022, Innovent Bio and Eli Lilly and Company announced a deepening of their strategic collaboration in the oncology field. Innovent Bio gained the rights to import, price, sell, promote, and distribute Cyramza in mainland China.^®(Ramucirumab) and Selpercatinib have been granted exclusive commercialization rights after approval, along with the priority negotiation rights for the future commercialization of Pirtobrutinib in mainland China.

About Innovent Bio

"Start with trust, achieve through action." Developing high-quality biologics that are affordable for the general public is the ideal and goal of Innovent Bio. Founded in 2011, Innovent Bio is committed to the research, production, and commercialization of innovative drugs in major disease areas such as oncology, autoimmune disorders, metabolic diseases, and ophthalmology. On October 31, 2018, INNOVENT BIOLOGICS(SUZHOU)CO LTD was listed on the Main Board of the Hong Kong Stock Exchange (Stock Code: 01801).

Since its establishment, the company has stood out among many biopharmaceutical companies with its innovative achievements and internationalized operating model. It has built a product chain comprising 34 new drug varieties, covering multiple disease areas such as oncology, metabolic diseases, and autoimmune diseases, seven of which have been selected for the national "Major New Drug Creation" program. The company already has eight products (Sintilimab Injection, trade name: Tyvyt).^®, English trademark: TYVYT^®; Bevacizumab biosimilar, brand name: Da You Tong^®, English trademark: BYVASDA^®; Adalimumab biosimilar, brand name: SULIXIN^®, English trademark: SULINNO^®; Rituximab biosimilar, brand name: Dabohua^®, English trademark: HALPRYZA^®; Pemigatinib Tablets, Trade Name: Dabotan^®, English trademark: PEMAZYRE^®; Orelabrutinib, Trade Name: Nulric^®; Ramucirumab, Trade Name: Cyramza^®, English trademark: CYRAMZA^®; Selpercatinib) has been approved for marketing, 2 products are under NMPA review, 4 products have entered Phase III or pivotal clinical trials, and another 20 products have entered clinical trials.

Innovent Bio has assembled a team of top-tier biopharmaceutical development and industrialization professionals with international advanced standards, including numerous overseas returnees. It has also established strategic partnerships with international collaborators such as Eli Lilly and Company, Sanofi, Adimab, Incyte, and MD Anderson Cancer Center. Innovent Bio hopes to work together with everyone to enhance the development level of China's biopharmaceutical industry, meeting the public's need for accessible medications and their aspirations for better life and health. For more information, please visit the company website:www.innoventbio.comOr company LinkedIn accountwww.linkedin.com/company/innovent-biologics/。

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References

[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] NHFPC "Guidelines for the Diagnosis and 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.