Astellas' Claudin-Targeted Gastric Cancer Therapy Gains FDA Approval

The U.S. Food and Drug Administration (FDA) recently approved a new treatment for gastric or gastroesophageal junction cancer, making it the first claudin 18.2-targeted therapy available in the country for these conditions. The drug, developed by Astellas Pharma and named Vyloy, is a cytolytic antibody, zolbetuximab-clzb.

Vyloy is specifically approved for use in adult patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. It is indicated for first-line treatment in patients whose tumors are claudin 18.2-positive and HER2-negative. The therapy is to be used in combination with chemotherapy agents that include fluoropyrimidine and platinum.

Dr. Samuel Klempner, a medical oncologist at Massachusetts General Hospital, emphasized that Vyloy's approval introduces a novel biomarker and a new treatment option for patients with claudin 18.2-positive tumors. These patients represent a group with a significant unmet need despite advances in first-line treatments for locally advanced unresectable and metastatic gastric and gastroesophageal junction cancers.

The FDA's approval of Vyloy is underpinned by data from two Phase III clinical trials, SPOTLIGHT and GLOW. These studies demonstrated that treatment regimens based on Vyloy significantly improve patient survival rates. Vyloy was generally well-tolerated in both trials, with the most common side effects being nausea, vomiting, and reduced appetite.

In the SPOTLIGHT study, Vyloy was tested in combination with the mFOLFOX6 regimen, which includes oxaliplatin, leucovorin, and fluorouracil. This combination was compared to a placebo plus mFOLFOX6. Data released by Astellas in January 2023 showed that the Vyloy regimen reduced the risk of disease progression or death by nearly 25%. The median progression-free survival for patients on Vyloy was 10.61 months, compared to 8.67 months for the placebo group. Additionally, overall survival was significantly longer for patients treated with the Vyloy combination.

Following the SPOTLIGHT study, Astellas presented data from the GLOW study in March 2023. This trial combined Vyloy with a chemotherapy regimen of capecitabine and oxaliplatin, commonly known as CAPOX. Compared to a placebo plus CAPOX, the Vyloy regimen reduced the risk of disease progression or death by more than 31% and the risk of death by nearly 23%.

Vyloy's approval faced initial challenges. In January 2024, the FDA initially rejected the application due to unresolved deficiencies at a third-party manufacturing facility. Importantly, the FDA did not find any issues with Astellas' clinical data or the safety profile of Vyloy. Astellas addressed these manufacturing concerns and resubmitted their application, which the FDA accepted in May 2024. The FDA set a target action date of November 9, and subsequently approved Vyloy.

This landmark approval marks a significant step forward in the treatment of gastric and gastroesophageal junction cancers, offering new hope for patients with limited options. The introduction of Vyloy as the first claudin 18.2-targeted therapy highlights the ongoing progress in oncology, aiming to improve patient outcomes through innovative treatment approaches.