First Domestic Bevacizumab Biosimilar Set for Approval: Qilu Pharmaceutical Leads the Race

On November 20, the review status of Qilu Pharmaceutical’s “bevacizumab biosimilar” (Acceptance No.: CXSS1800017) was updated to “Under Approval.” Following two rounds of supplementary data submissions and on-site inspections of clinical and production facilities, Insight predicts that approval for market launch is imminent, marking the successful emergence of the first domestically produced bevacizumab biosimilar.

Annual Sales of 6.8 Billion: "Blockbuster" Variety

Bevacizumab (Avastin) is a humanized anti-VEGF monoclonal antibody. As the first anti-angiogenic drug under Roche approved for widespread use across multiple tumor types globally, it inhibits tumor angiogenesis by blocking VEGF, thereby cutting off blood supply to the tumor region, suppressing tumor growth and metastasis, and exerting its antitumor effects.

The drug was first approved by the FDA in 2004, received approval in Europe in 2005, and was launched in China in 2010 for the treatment of metastatic colorectal cancer. In 2015, it was further approved by the NMPA for the treatment of non-small cell lung cancer. To date, it has been approved for multiple solid tumor indications, including colorectal cancer, non-small cell lung cancer, glioblastoma, renal cell carcinoma, cervical cancer, ovarian cancer, fallopian tube cancer, and peritoneal cancer.

As one of Roche’s “big three” monoclonal antibodies, this drug has dominated sales rankings for many years, with global sales reaching approximately CHF 6.849 billion in 2018. According to the Insight sales database, domestic sales of bevacizumab in China amounted to approximately RMB 1.5 billion in 2017.

The patent protection for bevacizumab in China expired in 2018. Currently, no biosimilars of bevacizumab are marketed in China; however, an increasing number of manufacturers are participating in the development of this blockbuster drug.

Over 30 domestic products in development, with intense competition

The Insight database shows that currently, three companies in China have marketing authorization applications under review, 16 are conducting clinical trials, eight have received clinical trial approval, and five are submitting clinical trial applications, indicating intense overall competition.

Tier 1: Qilu Leads the Pack

Qilu Pharmaceutical submitted the earliest marketing application, which was accepted in August 2018. According to the Insight Clinical Trials Database, the indicated indication is non-small cell lung cancer (NSCLC). In the QL1101 clinical trial (registration number: CTR20161024), the primary endpoint was the objective response rate (ORR) at Week 18, assessed using RECIST 1.1. A total of 512 subjects were recruited in China, with 532 ultimately enrolled. The first patient in China was enrolled on March 24, 2017.

Inxitec Biologics’ second application, submitted in January 2019, was accepted for review; the indicated indications are identical to those of Qilu Pharmaceutical, while clinical trials of sintilimab for advanced hepatocellular carcinoma are also ongoing.

Second Tier: 12 Companies in Phase III Clinical Trials

The Insight database shows that there are currently 12 companies in Phase III clinical trials, considered the second tier, and 5 companies in Phase I, considered the third tier.

Currently, there are 16 bevacizumab biosimilars in China that have advanced to Phase III clinical trials (including those from Innovent Biologics and Qilu Pharmaceutical). Among them, Hengrui Medicine, Henlius, Shandong Boan Biotechnology, Tanya Pharmaceuticals, TianGuangShi Biologics, Bio-Thera Solutions, and Anhui Anke Biotechnology have already initiated patient recruitment for clinical trials. Notably, Bio-Thera has registered an international multicenter clinical trial (indication: non-squamous non-small cell lung cancer), while Henlius has strategically selected colorectal cancer as its indication to differentiate itself.

Third Tier: 5 Companies in Phase I Clinical Trials

At this stage, to avoid homogenization, none of the companies have chosen non-small cell lung cancer (NSCLC) as their indication. Among them, 3SBio (indication: wet age-related macular degeneration), Taikang Bio (indication: neovascular (wet) age-related macular degeneration [AMD]), and Nanjing Simcere Dongyuan (indications: metastatic colorectal cancer, advanced or metastatic solid tumors) have already initiated clinical trial recruitment.

Conclusion

The 2017 National Reimbursement Drug List (NRDL) negotiations led to a significant price reduction for bevacizumab, decreasing from RMB 5,210 per vial (100 mg/4 mL) to RMB 1,998, thereby substantially improving its accessibility. With the sequential market launch of biosimilars, the financial burden on Chinese cancer patients for bevacizumab therapy is expected to be further alleviated.

Previously, Henlius’s rituximab biosimilar was approved for marketing, with its price set at only 60% of that of the originator product, significantly reducing the medication burden on patients. According to the Insight database, the latest winning bid price for the originator bevacizumab is RMB 1,934.26 per 4 mL (100 mg), and Qilu Pharmaceutical’s pricing is expected to range between RMB 1,000 and RMB 1,200.