AstraZeneca's Durvalumab (Imfinzi) Set to Become China's First Approved PD-L1 Monoclonal Antibody

On November 24, AstraZeneca’s PD-L1 inhibitor durvalumab injection (Imfinzi) had its marketing application in China under “review” status (Acceptance Numbers: JXSS1800040/JXSS1800041). It is expected to be approved imminently, becoming the first PD-L1 monoclonal antibody drug marketed in China, indicated for the treatment of unresectable stage III non-small cell lung cancer.

Imfinzi targets programmed death-ligand 1 (PD-L1), directly binding to the PD-L1 protein and inhibiting its interaction with PD-1 and CD80 on the surface of T cells, thereby preventing tumor cells from exploiting the PD-L1/PD-1 pathway to evade immune surveillance. Durvalumab leverages this mechanism to activate the immune system, thereby enhancing tumor cell killing.

In May 2017, the U.S. FDA approved AstraZeneca’s PD-L1 monoclonal antibody, Imfinzi, for the treatment of advanced or metastatic urothelial carcinoma. In February 2018, the U.S. FDA further approved Imfinzi for the treatment of patients with stage III unresectable, locally advanced non-small cell lung cancer (NSCLC) whose disease had not progressed following initial chemoradiotherapy. Imfinzi is the first therapy approved in nearly two decades to reduce the risk of disease progression in stage III unresectable NSCLC.

The approval of Imfinzi for unresectable stage III non-small cell lung cancer (NSCLC) was based on the phase III clinical study PACIFIC. PACIFIC is a randomized, double-blind, placebo-controlled phase III study that enrolled 713 patients with unresectable stage III NSCLC who had not progressed after concurrent chemoradiotherapy, and randomly assigned them to receive either Imfinzi or placebo.

The results of the PACIFIC study were presented at the 2017 ESMO Congress. Compared with the placebo group, Imfinzi significantly prolonged progression-free survival (PFS) by more than 11 months (16.8 months vs. 5.6 months; HR=0.52; 95% CI: 0.42–0.65). Imfinzi is the first immune checkpoint inhibitor to demonstrate a significant PFS benefit in patients with stage III non-small cell lung cancer (NSCLC).

Furthermore, results from the Phase II Atlantic clinical trial evaluating Imfinzi as third-line or later treatment for advanced NSCLC demonstrated that the anti-PD-L1 monoclonal antibody Imfinzi exhibits favorable clinical efficacy and good tolerability in patients with advanced non-small cell lung cancer who have previously undergone multiple lines of therapy. Durable efficacy and improved overall survival were observed regardless of EGFR/ALK mutation status or PD-L1 expression levels.

On December 26, 2018, the Center for Drug Evaluation (CDE) officially accepted the marketing application for AstraZeneca’s PD-L1 monoclonal antibody, Durvalumab. Following a round of requests for supplementary information in August this year, the drug remained under “under review” status for less than one year (353 days).

JXSS1800040 Marketing Authorization Review Timeline

Currently, Imfinzi is conducting multiple clinical trials globally. In China, trials for hepatocellular carcinoma, advanced urothelial carcinoma, and limited-stage small cell lung cancer have all entered Phase III clinical development.

Imfinzi Global Clinical Trials (https://db.dxy.cn)

Imfinzi Clinical Trials in China (https://db.dxy.cn)

Currently, three PD-L1 monoclonal antibody drugs have been approved globally: Roche’s atezolizumab (Tecentriq), Merck/Pfizer’s avelumab (Bavencio), and AstraZeneca’s durvalumab (Imfinzi). None of these three agents have currently received import approval in China, where only PD-1 monoclonal antibodies have been approved.

According to the Insight database, in addition to the impending approval of Imfinzi, Roche’s Tecentriq also submitted its marketing application in China on February 22, 2019 (Acceptance Number: JXSS1900004). It is currently undergoing the first round of supplementary data review and is expected to gain approval by early next year. At that time, there are likely to be eight PD-1/PD-L1 monoclonal antibody drugs available simultaneously in the Chinese market.

Insight database shows that there are currently 15 types of PD-L1 antibodies under clinical development by domestic companies in China (involving 54 clinical trial registration numbers), including 15 companies such as Sino Biopharmaceutical, Innovent, Kelun, and Hengrui. Among them, the first-tier domestically produced candidates in Phase III clinical trials include Hengrui’s SHR-1316 injection, Sino Biopharmaceutical’s TQB2450 injection, CStone Pharmaceuticals’ CS1001, and Sichuan Sidelis’ KN035.