Astellas Pharma recently filed new drug application (NDA) in Japan for zolbetuximab, a novel chimeric immunoglobulin G1 antibody highly specific for Claudin 18 isoform 2 (CLDN18.2) for the first-line treatment of gastric cancer patients. Following approval, the drug is expected to have limited potential in the first-line treatment setting, considering the clinical success of its competitor Bristol Myers Squibb’s Opdivo (nivolumab), says GlobalData, a leading data and analytics company.

Gastric cancer is the third leading cause for cancer deaths in Japan, resulting in approximately 50,000 deaths per year. According to GlobalData’s Pharmaceutical Intelligence Center, Japan witnesses the second highest diagnosed prevalent cases of gastric cancer among the 16 major markets (16MM*) after China. The diagnosed prevalent cases of gastric cancer in Japan are expected to increase at a compound annual growth rate (CAGR) of approximately 1% from 458,365 in 2023 to 482,331 in 2028.

Neha Myneni, Pharma Analyst at GlobalData, comments: “With Opdivo being the only marketed immunotherapy available in the market for first-line treatment setting, there exists a significant unmet need for HER2-negative gastric cancer patients in Japan. Zolbetuximab’s likely approval will certainly become a significant milestone in gastric cancer treatment in the country.

“However, due to its niche target patients (CLDN18.2 mutations detected in about 30% of HER2-negative gastric cancer patients), zolbetuximab success in terms of market penetration is likely to be less compared to Opdivo.”

Astellas filed NDA based on zolbetuximab’s Phase III trials (SPOTLIGHT and GLOW), where the drug was evaluated in combination with chemotherapies mFOLFOX6 (oxaliplatin, leucovorin and fluorouracil) and CAPOX (capecitabine and oxaliplatin), respectively.

Nivolumab was approved for first-line treatment of unresectable advanced or recurrent gastric cancer in combination with chemotherapy in Japan in 2021 based on results from the two ongoing Phase III studies CheckMate-649 and ATTRACTION-4.

Myneni concludes: “Astellas will certainly have a first-to-market advantage with its anti-claudin therapy supported by lack of late-stage pipeline drugs currently under development for this target. However, limited target population and early market entry advantage of Opdivo might impact physician’s decision to switch their eligible patients to zolbetuximab.

“Astellas should prioritize addressing the absence of companion diagnostic solutions to mitigate testing challenges faced by potential zolbetuximab patients. Additionally, the company’s strategic emphasis on label expansion, including ongoing Phase II trials for pancreatic cancer, holds promise for enhancing market success, pending approval.”

*16MM: Australia, Brazil, Canada, China, France, Germany, India, Italy, Japan, Mexico, Russia, South Africa, South Korea, Spain, the UK, and the US.