Source – Astellas Pharma
On July 6 2023, Astellas Pharma announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review to its Biologics License Application (BLA) for zolbetuximab. This investigational monoclonal antibody targets Claudin 18.2 (CLDN18.2) and, if approved, would be the first therapy of its kind available in the US for patients with advanced gastric and gastroesophageal cancers.
Gastric cancer, also known as stomach cancer, ranks as the fifth most diagnosed cancer worldwide. In the US alone, around 26,500 individuals are expected to be diagnosed with gastric cancer in 2023, with 11,130 deaths projected. Early-stage gastric cancer symptoms often overlap with more common stomach-related conditions, resulting in late-stage diagnosis when the disease has already advanced or metastasized to other tissues or organs.
The five-year survival rate for patients with metastatic gastric cancer is only 6.6%.
Zolbetuximab is intended for first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma, whose tumors test positive for CLDN18.2. Zolbetuximab works by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. Preclinical studies have shown that this binding induces cancer cell death by activating two immune system pathways: antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
The BLA submission is based on data from the Phase III SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study compared zolbetuximab plus mFOLFOX6 (a combination regimen with oxaliplatin, leucovorin, and fluorouracil) to placebo plus mFOLFOX6, while the GLOW study compared zolbetuximab plus CAPOX (a combination chemotherapy regimen with capecitabine and oxaliplatin) to placebo plus CAPOX. In both studies, approximately 38% of screened patients had CLDN18.2-positive tumors, as determined by a validated immunohistochemistry assay.
“Astellas is committed to bringing innovative therapies to patients with hard-to-treat cancers, including gastric cancer. While rare in the US gastric cancer can be deadly when diagnosed in the late stages. The FDA’s acceptance of the Biologics License Application filing and Priority Review designation for zolbetuximab confirms the urgent therapeutic need and brings us one step closer to delivering on this commitment to patients, families and caregivers.”
– Moitreyee Chatterjee-Kishore, PhD, MBA, Senior Vice President and Head of Immuno-Oncology Development, Astellas
The FDA reviewed the application under its Real-Time Oncology Review (RTOR) program, which aims to expedite the review process to make safe and effective treatments available to patients as early as possible.
The FDA has set a target action date of January 12, 2024, under the Prescription Drug User Fee Act (PDUFA), and Astellas has already included the impact of this acceptance in its financial forecast for the current fiscal year, ending March 31, 2024.
