Vyloy Approved for Stomach Cancer

On Oct. 18, 2024, the U.S. Food and Drug Administration (FDA) approved Astellas Pharma’s Vyloy^® (zolbetuximab-clzb) for use in combination with fluoropyrimidine- and platinum-containing chemotherapy (chemo) for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Vyloy is a claudin (CLDN)18.2-directed cytolytic antibody that is indicated in patients whose tumors test positive for CLDN18.2 on an FDA-approved test. It is the first targeted therapy approved by the FDA for patients with CLDN 18.2-positive tumors. The recommended dose of Vyloy, administered as an intravenous (IV) infusion, is 800mg/m² followed by 600mg/m² every three weeks or 400mg/m² every two weeks. Launch date and pricing information are not currently available. Full prescribing information can be found here.

At a Glance

• Brand Drug: Vyloy^® (zolbetuximab-clzb)
• Manufacturer: Astellas Pharma
• Date Approved: Oct. 18, 2024
• Indication:  For use in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative G/GEJ adenocarcinoma whose tumors are CLDN18.2 positive as determined by an FDA-approved test
• Dosage Forms Available: 100mg lyophilized powder in single-dose vials for reconstitution, dilution, and IV infusion
• Launch Date: The launch date isn’t known at this time.
• Estimated Annual Cost: Pricing information is not yet available.
• G/GEJ cancer is a type of cancer that starts in the stomach or where the stomach and esophagus meet. These types of cancers tend to develop slowly, and symptoms may include indigestion, pain in the abdomen, nausea, vomiting, bloating after meals, and loss of appetite. Since these symptoms frequently overlap with common stomach conditions, this type of cancer is often diagnosed at the advanced or metastatic stage where symptoms may include unexplained weight loss, vomiting blood or having blood in the stool.
• G/GEJ is the fifth most commonly diagnosed cancer worldwide however is considered a rare disease in the US. It is estimated that there are 130,263 Americans currently living with G/GEJ cancer. Based on the clinical studies, it is estimated that 30-40% of patients with G/GEJ will be both CLDN18.2 positive and HER2-negative and therefore eligible for treatment with Vylov. In 2024, it is estimated that 26,890 people will be diagnosed with G/GEJ cancer and 10,880 will die from the disease in the US.
• The approval of Vyloy was based on two clinical studies that showed that when Vyloy was added to an appropriate chemo regimen it significantly improved the patient’s progression-free survival and overall survival by about two months each when compared to the chemo regimens alone.
• Vylov is a first-in-class CLDN18.2-specific targeted therapy; therefore, there are no direct competitors. Treatments are dependent on the stage of cancer and tumor expression. Other treatments for G/GEJ may include programmed cell death 1 (PD-1) inhibitors like Opdivo^® (nivolumab – Bristol Myers Squibb) or Keytruda^® (pembrolizumab – Merck), or anti-HER2 antibodies like Enhertu^® (fam-trastuzumab deruxtecan-nxki – Daiichi Sankyo/AstraZeneca) or Herceptin^® (trastuzumab – Genentech). 
• Vylov is in Phase II studies in combination with nab-paclitaxel and gemcitabine (Nab-P + GEM) as a first-line treatment in patients with CLDN18.2-positive, metastatic pancreatic cancer.
• The FDA also approved the Ventana^® CLDN18 (43-14A) RxDx Assay test developed by Roche. This is a companion diagnostic to identify patients who may be eligible for Vyloy.