CAP files amicus brief in LDT lawsuits
November 2024—The College of American Pathologists on Oct. 7 filed an amicus brief in support of the plaintiffs in the consolidated cases American Clinical Laboratory Association, et al., v. U.S. Food and Drug Administration, et al., and Association for Molecular Pathology, et al., v. U.S. Food and Drug Administration, et al.
Plaintiffs in these consolidated cases challenge a final rule setting out the FDA’s plan to regulate LDTs as medical devices under the Federal Food, Drug and Cosmetic Act. “The Final Rule imposes draconian new restrictions—and crushing compliance costs—on the development and use of LDTs,” the CAP says in its amicus brief.
The CAP says in the brief that its “keen interest and deep experience in the practical issues surrounding LDT regulation will benefit the Court’s decisionmaking in this case.” In taking its “drastic action,” the CAP says of the FDA, it “failed to engage in the reasoned decisionmaking that the Administrative Procedure Act demands.”
The brief adds: “Reasonable regulation requires that an agency grapple with the negative consequences of its chosen path. Here, FDA instead found a way to ignore those consequences by asserting that its novel, complex, and nonbinding scheme of ‘enforcement discretion policies’ articulated in the Final Rule’s preamble would prevent the catastrophic consequences that so many stakeholders have predicted.” Yet the final rule never explains how the FDA’s “slew of explicitly nonbinding policies” will safeguard LDT innovation and patient access, the CAP says.
The CAP urged the U.S. District Court for the Eastern District of Texas to vacate the final rule as arbitrary and capricious.
CAP president Donald Karcher, MD, said the CAP filed the amicus brief because CAP members “fear these regulatory restrictions from the FDA will delay the diagnosis of disease and treatment of patients.” He added: “The CAP had communicated its concerns to the FDA prior to the release of the final rule and urged the agency to take a different tact. However, the FDA moved forward and now pathologists and their laboratories are having conversations about which LDTs will no longer be available to patients in their communities. The FDA’s failure to come to grips with the obvious ramifications on patients of the LDT regulation clearly renders the rulemaking arbitrary and capricious.”
The FDA on Oct. 25 filed a brief defending its regulation of LDTs and asking the court to grant its motion for summary judgment and to deny the plaintiffs’ cross-motions. The court granted the FDA’s request.
CDx approved for patients with gastric and GEJ cancers
Roche received Food and Drug Administration approval in October for the first companion diagnostic to identify patients with gastric and gastroesophageal junction cancer who may be eligible for targeted treatment with zolbetuximab (Vyloy).
The Ventana Claudin 18 (43-14A) RxDx assay is an FDA-approved immunohistochemistry companion diagnostic for determining CLDN18 protein expression in tumors of patients with gastric or GEJ adenocarcinoma.
The Roche test measures expression of both variants of the CLDN18 protein (18.1 and 18.2 isoforms). CLDN18.2 is the predominant variant expressed in gastric and GEJ cancers.
The approval of the Ventana CLDN18 (43-14A) RxDx assay is based on the results of the Spotlight and Glow clinical studies, in which it was used as the enrollment assay to identify patients whose tumors were CLDN18.2 positive. CLDN18.2 positivity is defined as greater than or equal to 75 percent of tumor cells demonstrating moderate to strong membrane CLDN18 staining as measured by the Ventana CLDN18 assay. In these studies, about 38 percent of gastric/GEJ cancer patients expressed high levels of CLDN18 and were considered CLDN18.2 positive by the Ventana CLDN18 assay. Patients who received a combination of zolbetuximab and chemotherapy experienced a 25 to 31 percent reduction in disease progression or death.
Fassan M, et al., in a recently published review of CLDN18.2 IHC evaluation in gastric and GEJ adenocarcinomas to direct targeted therapy, provide practical guidance on CLDN18.2 testing and scoring (Fassan M, et al. Mod Pathol. 2024;37[11]:100589).