An Astellas Pharma drug designed to address a novel target has landed a highly anticipated FDA approval for a rare type of gastrointestinal cancer, making it the first therapy in a new class of oncology drugs.
The regulatory decision announced Friday covers the first-line treatment of adults with advanced cases of gastric or gastroesophageal junction (GEJ) adenocarcinoma. These cancers must express the cancer protein claudin 18.2 (CLDN18.2), the target of the Astellas antibody, zolbetuximab. The Japanese pharmaceutical company will market the new drug under the brand name Vyloy.
GEJ adenocarcinoma is a type of cancer in the area where the esophagus joins the stomach. According to Astellas, an estimated 130,263 people in the U.S. are living with gastric or GEJ cancer, which places it among the rarer cancers. CLDN18.2 is found only in stomach cells, not other healthy tissues. In gastrointestinal cancers, this protein is overexpressed, making it a valuable target for cancer drugs. Vyloy binds to CLDN18.2, activating two immune system pathways that kill cells expressing the target protein.
FDA approval of Vyloy covers the treatment of gastric or GEJ cancers that are negative for a different cancer protein called HER2. That’s important because cancers positive for HER2 already have treatment options, such as Roche’s HER2-binding antibody, Herceptin, and the AstraZeneca and Daiichi Sankyo antibody drug conjugate (ADC) Enhertu. Vyloy’s approval gives HER2-negative gastric and GEJ cancers patients a targeted treatment option for use in combination with standard of care chemotherapies.
Astellas’s submission for Vyloy was based on results from two Phase 3 clinical trials that enrolled participants with advanced HER2-negative gastric or GEJ cancer that was positive for CLDN18.2. One study evaluated Vyloy in combination with the chemotherapy regimen known as FOLFOX6, comparing it to a placebo and FOLFOX6; the other trial tested the study drug and the chemo regimen known as CAPOX against a placebo and CAPOX.
In both studies, the combination of Vyloy and chemo led to statistically significant improvement on the main goal of progression-free survival. The studies also achieved statistically significant improvement on the key secondary goal of overall survival. The most common side effects reported in these studies included nausea, vomiting, and decreased appetite. In Astellas’s announcement of Vyloy’s approval, Dr. Samuel Klempner, associate professor at Harvard Medical School and a medical oncologist at Massachusetts General Hospital, said that despite advances in first-line treatment of advanced gastric and GEJ cancers, there is still an unmet medical need for these patients.
“The approval of Vyloy, based on the pivotal Phase 3 SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive, and for those on the frontlines of treatment decision-making,” he said.
Vyloy was initially expected to receive an FDA decision early this year, but the agency rejected the drug’s application in January due to issues with the drug’s third-party manufacturer. The approval came ahead of the new Nov. 9 target date for a decision. Concurrent with the Vyloy approval, the FDA also approved a Roche companion diagnostic to identify patients eligible for treatment with the drug.
Astellas gained Vyloy from its 2016 acquisition of privately held Ganymede Pharmaceuticals for €422 million (about $462 million) up front. Another €860 million (about $930 million) is tied to the achievement of milestones. With the FDA approval of Vyloy, the U.S. is now the fifth market for the new Astellas drug. Japan was the first country to approve the drug in a regulatory decision handed out in March. Since then, Vyloy has landed affirmative regulatory decision in the United Kingdom, South Korea, and the European Union. The drug is still under review in other markets around the world.
There are other companies pursuing CLDN18.2. In 2023, AstraZeneca licensed a CLDN18.2-targeting ADC from KYM Biosciences for $63 million up front. This program, since renamed AZD0901, began a Phase 3 study earlier this year evaluating the drug as a second-line treatment for advanced gastric and GEJ cancers.
The contender of Boston-based Elevation Oncology is EO-3021, an ADC currently in early-stage clinical development as a monotherapy for advanced solid tumors, including gastric, GEJ, pancreatic, and esophageal cancers. Data from this study are expected in the first half of 2025. A separate ongoing Phase 1 test is evaluating the Elevation drug in combination with Eli Lilly’s Cyramza and GSK’s Jemperli. Meanwhile, Merck KGaA could get a CLDN18.2 drug via a 2023 deal that granted it an option to license an ADC in development by Jiangsu Hengrui Pharmaceuticals.
Photo: Kiyoshi Ota/Bloomberg, via Getty Images
