After clearing reimbursement review on its second attempt, Astellas’ Vyloy (zolbetuximab) is expected to reshape the metastatic gastric cancer treatment landscape.

The entry of a targeted therapy option into a market previously dominated by immuno-oncology drugs presents a dilemma for treatment selection in clinical practice.

#According to industry sources on the 3rd, the Health Insurance Review and Assessment Service (HIRA) recently convened its 8th Cancer Disease Deliberation Committee to review reimbursement criteria for major anticancer drugs submitted for consideration.

At this meeting, Vyloy, the first-in-class CLDN18.2-targeted therapy, successfully established reimbursement criteria, and the application will now move up for review by the Drug Reimbursement Evaluation Committee.

The indication approved for reimbursement is as ‘first-line treatment, in combination with fluoropyrimidine- and platinum-based chemotherapy, for patients with unresectable locally advanced or metastatic CLDN18.2-positive, HER2-negative gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.

The current treatment landscape for metastatic gastric cancer is dominated by immuno-oncology drugs.

Specifically, Opdivo (nivolumab) is currently reimbursed in domestic clinical settings and is considered a first-line treatment option. Patients with PD-L1 expression levels of ‘CPS 5 or higher’ are granted Opdivo use with reimbursement.

The other two options (Keytruda, Tevimbra) remain non-reimbursed. Under the recently revised partial coverage policy for combination anticancer therapies, only existing platinum and fluoropyrimidine-based chemotherapy regimens qualify for ‘partial coverage (5/100)’, while immuno-oncology drugs remain uncovered.

However, Keytruda is currently undergoing price negotiations with the National Health Insurance Service for metastatic gastric cancer indications, with coverage expected in the first half of next year.

However, Keytruda's situation is not so rosy. As its reimbursement criteria were set at ‘CPS 10 or higher,’ meaning its listing could actually impose greater restrictions on its use relative to Opdivo.

In such a context, the industry believes that Vyloy would be sufficiently competitive if it were to be covered.

Furthermore, according to the integrated analysis of the SPOLIGHT and GLOW studies presented at last year's European Society for Medical Oncology Annual Congress 2024 (ESMO 2024), the median progression-free survival (PFS) was 9.2 months in the Vyloy-chemotherapy combination group and 8.2 months in the placebo group. The median overall survival (OS) was 16.4 months in the Vyloy combination group and 13.7 months in the placebo group.

Subsequent analysis of the Korean subgroup showed that the Vyloy combination group's mPFS and mOS were 12.6 months and 30.0 months, respectively. This is a marked improvement compared to the results previously published in the global study.

Having passed the National Health Insurance Service (NHIS) review, if reimbursement is approved, as nearly 40% of all gastric cancer patients express Claudin-18.2, clinicians may consider between Vyloy and immuno-oncology drugs.

Professor Minkyu Jung (Department of Medical Oncology) at Yonsei Cancer Hospital stated, “For clinicians, a major dilemma arises when a patient is both Claudin-18.2 and PD-L1 positive: which agent should be used first?” He added, “For patients who are Claudin18.2-positive and have a PD-L1 CPS (Combined Positive Score) between 5 and 10, the hazard ratio confirmed for Vyloy is 0.77, lower than that for immuno-oncology drugs. If reimbursement status is not a factor, many oncologists prefer using Vyloy in that patient group.

He emphasized, “Claudin18.2 is a biomarker expressed in gastric and pancreatic cancers. It may be a pivotal biomarker in the entire gastric cancer treatment paradigm.”