The FDA has issued a Complete Response Letter for TLX250-CDx (Zircaix), rejecting the biologics license application for this breakthrough therapy-designated PET imaging agent due to chemistry, manufacturing, and controls deficiencies rather than clinical efficacy concerns. Telix believes these manufacturing comparability issues are readily addressable, maintaining the drug’s potential as the first commercial imaging agent for clear cell renal cell carcinoma diagnosis.
Drug Profile & Mechanism:
- TLX250-CDx (Zircaix®, 89Zr-DFO-girentuximab) – first-in-class biologic-based PET imaging agent using 89Zr isotope
- Target mechanism: Binds to carbonic anhydrase IX, expressed on 95% of clear cell renal cell carcinoma cells
- Patient population: Adults with renal masses requiring characterization for ccRCC diagnosis
- Developer: Telix Pharmaceuticals Limited (ASX: TLX, NASDAQ: TLX)
Regulatory Milestone Details:
- CRL issued: August 28, 2025, citing Chemistry, Manufacturing, and Controls (CMC) package deficiencies
- Core issue: FDA requested additional data establishing comparability between ZIRCON Phase 3 trial drug product and scaled-up commercial manufacturing process
- Additional concerns: Form 483 notices of deficiency issued to two third-party manufacturing/supply chain partners requiring remediation
- Current designations maintained: Breakthrough Therapy Designation (July 2020) and Priority Review status remain active
Practice Implications:
- Patient access continues: FDA-approved expanded access program (EAP) remains available subject to FDA consultation
- No immediate clinical impact: Rejection based on manufacturing comparability, not clinical efficacy or safety concerns
- Diagnostic gap persists: ccRCC remains without a commercially available, non-invasive diagnostic imaging agent
- Treatment planning: Current imaging modalities continue as standard of care for renal mass characterization
Development Status & Next Steps:
- Immediate remediation: Company initiating submission remediation process immediately
- Type A meeting requested: Telix seeking FDA meeting to address deficiencies and establish resubmission timeline
- Company confidence: Management believes concerns are “readily addressable within reasonable timeframe”
- Financial impact: No effect on 2025 revenue guidance, which excluded unapproved product forecasts
- Supply chain complexity: Highlights regulatory challenges for novel radiopharmaceuticals with complex manufacturing requirements
Source: https://ir.telixpharma.com/static-files/6264a633-04e6-4eb2-81c5-f9fc40d113d2
