The regulator’s approval on Friday of Vyloy for gastric or gastroesophageal junction cancer makes it the first and only claudin 18.2–targeted therapy approved in the U.S. for these indications, according to Astellas.
The FDA on Friday signed off on Astellas Pharma’s cytolytic antibody zolbetuximab-clzb, now to be marketed as Vyloy, for the treatment of adult patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Vyloy is the first and only claudin 18.2–targeted therapy approved in the U.S. for these indications, according to Astellas. Vyloy’s label covers its first-line use in claudin 18.2–positive patients with HER2-negative tumors, and in combination with fluoropyrimidine- and platinum-containing chemotherapy.
Samuel Klempner, medical oncologist at the Massachusetts General Hospital in Boston, said in a statement that Vyloy’s approval “brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive,” for whom “there is still a tremendous unmet need” despite substantial “advancements in the first-line treatment of locally advanced unresectable and metastatic gastric and GEJ (gastroesophageal junction) cancers.”
Klempner has previously served as a consultant or advisor to Astellas.
Friday’s approval is backed by data from the Phase III SPOTLIGHT and GLOW studies, which together demonstrate that Vyloy-based treatment regimens could significantly improve survival in patient. In both studies, Vyloy was well-tolerated with the most common toxicities including nausea, vomiting and weakened appetite.
In SPOTLIGHT, Vyloy was combined with mFOLFOX6—a treatment regimen that includes oxaliplatin, leucovorin and fluorouracil—and tested against placebo plus mFOLFOX6. Astellas released data from the study in January 2023, touting a nearly 25% reduction in the risk of disease progression or death. Median progression-free survival at the time was 10.61 months in the Vyloy arm, compared to 8.67 months in the placebo group.
Overall survival was also significantly longer in patients treated with the Vyloy combo.
Astellas followed the SPOTLIGHT readout with a data drop from GLOW in March 2023, which combined Vyloy with the chemo combo of capecitabine and oxaliplatin, better known as CAPOX. Compared with placebo plus CAPOX, the Vyloy regimen lowered the risk of disease progression or death by more than 31% and the risk of death by nearly 23%.
Vyloy’s approval on Friday comes after an initial rejection in January 2024. At the time, the FDA noted unresolved deficiencies with a third-party manufacturing facility—though the regulator did not find problems with Astellas’ data or Vyloy’s safety. Astellas subsequently resubmitted its application, which the FDA accepted in May 2024 and gave a target action date of Nov. 9.
