FDA Issues Complete Response Letter for Telix’s PET Imaging Agent

The U.S. Food and Drug Administration (FDA) has declined to approve the biologics license application (BLA) for 89Zr-DFO-girentuximab (Zircaix; TLX250-CDx), an investigational PET imaging agent for clear cell renal cell carcinoma (ccRCC), according to a statement from Telix Pharmaceuticals.

The agency issued a complete response letter (CRL) citing deficiencies in the Chemistry, Manufacturing, and Controls (CMC) package. Specifically, the FDA noted Form 483 observations at two third-party manufacturing and supply chain partners that must be addressed before resubmission. In addition, regulators requested more data to demonstrate comparability between the drug used in the phase 3 ZIRCON trial and the product from Telix’s scaled-up commercial process.

Telix confirmed it will begin remediation efforts immediately and intends to schedule a Type A meeting with the FDA to outline corrective actions and establish a timeline for resubmission.

“TLX250-CDx breaks new ground as a highly novel biologic-based PET imaging agent using a first-in-class isotope,” said Christian Behrenbruch, Managing Director and Group CEO of Telix. “Like many radiopharmaceuticals, it has a complex supply chain. We believe these issues are resolvable and can be addressed within a reasonable timeframe.”

Key Takeaways:

• The FDA's complete response letter highlights deficiencies in the Chemistry, Manufacturing, and Controls package for 89Zr-DFO-girentuximab.
• Telix plans to address FDA concerns and schedule a Type A meeting to discuss resubmission timelines.
• 89Zr-DFO-girentuximab demonstrated high sensitivity and specificity in detecting ccRCC in the ZIRCON phase 3 trial.
• Safety data showed mostly mild adverse events, with serious events primarily occurring after surgery.

89Zr-DFO-girentuximab, a zirconium-labeled monoclonal antibody targeting carbonic anhydrase IX (CAIX), previously received Breakthrough Therapy and priority review designations. Despite the FDA’s request for additional data and remediation, Telix emphasized confidence in the agent’s clinical utility and regulatory prospects.

The company plans to work closely with the FDA to resolve outstanding issues and advance the resubmission of Zircaix for commercial approval.