TrialWatch: Innovent’s Bevacizumab Biosimilar ibi305 Meets Primary End-Points in Phase 2 Clinical Trials

Innovent, a Chinese biologics developer, reports that its proposed bevacizumab candidate, IBI305, has met primary end points in 2 randomized, head-to-head clinical trials that compared the biosimilar to the brand name bevacizumab (Avastin).   Bevacizumab, sold under the trade name Avastin, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer it is given by slow injection into a vein and used for colon cancerlung cancerglioblastoma, and renal-cell carcinoma. For age-related macular degeneration it is given by injection into the eye.

Common side effects when used for cancer include nose bleeds, headache, high blood pressure, and rash. Other severe side effects include gastrointestinal perforation, bleeding, allergic reactionsblood clots, and an increased risk of infection. When used for eye disease side effects can include vision loss and retinal detachment. Bevacizumab is in the angiogenesis inhibitor and monoclonal antibody families of medication. It works by slowing the growth of new blood vessels.

Bevacizumab was approved for medical use in the United States in 2004 It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. It is listed for its use in treating eye disease. The wholesale cost in the developing world is about US$638.54 per vial. This dose in the United Kingdom cost the NHS about £242.66 in 2015.

According to the Center for Biosimilars article, “Lung cancer is the highest incidence cancer in China, and bevacizumab is an important treatment for non-small lung cancer patients. The launch of a high-quality bevacizumab biosimilar will improve drug accessibility and benefit more patients,” said Li Zhang, MD, from the cancer hospital of Sun Yat-Sen University, in a statement announcing the positive top-line results.

The first study of IBI305 is a randomized, multicenter, double-blind, parallel, positive-controlled phase 3 trial in 450 patients with advanced non-squamous non–small cell lung cancer (NSCLC). This trial evaluated the efficacy and safety of IBI305 versus the reference bevacizumab as first-line treatment, in combination with paclitaxel/carboplatin, for NSCLC. According to Innovent, the biosimilar met its primary end of objective response rate.

The second trial, a randomized, double-blind, parallel, positive-controlled single-dose study, compared the pharmacokinetic profile, safety, tolerability, and immunogenicity of the biosimilar and the reference in 100 healthy volunteers. Innovent says that the study met its primary end point of demonstrating similar pharmacokinetics profiles between the two drugs.

Innovent has also been developing another approach to treating NSCLC, and in October 2018 was granted approval from China’s National Medical Products Administration to test a combination therapy comprising IBI305 plus sintilimab, an anti–programmed cell death protein 1 (PD-1) monoclonal antibody that has been jointly developed by Innovent and Eli Lilly.

According to Innovent, the relationship between vascular endothelial growth factor—targeted by bevacizumab—and tumor-induced immunosuppression driven by PD-1 is a promising target in both NSCLC and hepatocellular carcinoma. Abnormal tumor-induced angiogenesis appears to limit the therapeutic effect of anti–PD-1 antibodies and other immunotherapy products, and Innovent hopes the combination of sintilimab and biosimilar bevacizumab will be better able to control tumor growth by stimulating the immune system with an anti–PD-1 agent and blocking angiogenesis with bevacizumab.