FDA grants Priority Review of Astellas’ zolbetuximab BLA


Astellas Pharma Inc has announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review of its zolbetuximab Biologics License Application (BLA). If approved, the first-in-class investigational Claudin 18.2 (CLDN18.2)-targeted monoclonal antibody would be the first CLDN18.2-targeted therapy available in the US for patients with advanced gastric and gastroesophageal cancers.

Gastric cancer, more commonly known as stomach cancer, is the fifth most diagnosed cancer in the world. In the US alone, roughly 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023. Frequently, early-stage gastric cancer symptoms overlap with more common stomach-related conditions. This often results in gastric cancer diagnosis occurring in the advanced or metastatic stage, or once it has spread from the tumour origin to other body tissues or organs.

The five-year survival rate for patients at the metastatic stage is 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 tumours are CLDN18.2-positive. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

The BLA is based on results from the phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 – a combination regimen that includes oxaliplatin, leucovorin, and fluorouracil – compared to placebo plus mFOLFOX6.

The GLOW study evaluated zolbetuximab plus CAPOX – a combination chemotherapy regimen that includes capecitabine and oxaliplatin – compared to placebo plus CAPOX.

In both studies, approximately 38% of patients screened for the trials had tumours that were CLDN18.2-positive, as determined by a validated immunohistochemistry assay.

The FDA reviewed the application under its Real-Time Oncology Review (RTOR) programme, which aims to explore a more efficient review process to ensure that safe and effective treatments are made available to patients as early as possible.

Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of 12th January 2024 and Astellas has already reflected the impact of this acceptance in its financial forecast of the current fiscal year ending 31st March 2024.

Moitreyee Chatterjee-Kishore, senior vice president and head of immuno-oncology development at Astella, said: “Astellas is committed to bringing innovative therapies to patients with hard-to-treat cancers, including gastric cancer […] 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.”

At ASCO 2023, pharmaphorum editor-in-chief Jonah Comstock spoke with Mark Reisenauer, president of US commercial at Astellas. Reisenauer gave an update on some of Astellas’s abstracts at the show, including the trials in gastric cancer, bladder cancer, and head and neck cancer. Watch the video here or below.