FDA Issues CRL to TLX101-CDx, a Novel PET Imaging Agent for Glioma

US FDA

• The FDA has issued a complete response letter (CRL) to the new drug application (NDA) of TLX101-CDx (Pixclara; 18F-floretyrosine [18F-FET]) for glioma treatment.
• The FDA requires more clinical evidence to approve the agent.
• TLX101-CDx targets LAT1 and LAT2 proteins, enabling clearer differentiation between tumor recurrence and post-treatment changes.

The FDA has issued a CRL to the NDA of TLX101-CDx, a novel PET imaging agent developed by Telix Pharmaceuticals. The agent is intended for the detection and differentiation of glioma.¹

In the CRL, the FDA stated it required additional confirmatory clinical evidence to approve the application, "despite a robust consultation process prior to submission and during review of the NDA," stated Telix in a press release.

"This is a disappointing outcome for American glioma patients. FET-PET is recommended medical best practice in relevant international oncology practice guidelines and is used extensively in other parts of the world. The FDA has granted TLX101-CDx Orphan Drug and Fast Track designation, a tacit acknowledgement of the drug candidate's importance in addressing a significant unmet medical need and clinically demonstrating benefit over existing medical solutions," the press release continued.

TLX101-CDx is an amino acid PET imaging agent for brain cancer.² The agent targets membrane transport proteins LAT1 and LAT2, which are overexpressed in glioma cells, enabling clearer differentiation between progressive or recurrent glioma and post-treatment changes in both adult and pediatric patients.

The agent is designed to help distinguish tumor recurrence from treatment-related changes. By providing clearer imaging, the agent enables more accurate treatment planning.

In addition to its diagnostic capabilities, TLX101-CDx holds promise as a companion diagnostic for TLX101, an investigational small molecule therapy for glioblastoma currently in clinical development. TLX101, which also targets LAT1 and LAT2 transport proteins, is designed to cross the blood-brain barrier, offering a potential dual approach to diagnosing and treating glioma.

TLX101 is being evaluated in 2 ongoing clinical trials:

• IPAX-2 (NCT05450744): A phase 1 trial investigating TLX101 in combination with standard of care for newly diagnosed glioblastoma.³
• IPAX-Linz-01 (EudraCT2021-006426-43): A phase 2 trial evaluating TLX101 with concomitant external radiation therapy in patients with recurrent IDH1/2-mutated high-grade glioma.⁴

TLX101-CDx previously received orphan drug designation from the FDA in 2020 and fast track designation in 2024. The agent was also granted priority review by the FDA in October 2024.²

Beyond glioma imaging, TLX101-CDx is being explored as a companion diagnostic for TLX101-Tx, an investigational neuro-oncology therapeutic that leverages the same amino acid transporter mechanism but uses therapeutic radiation for treatment.

REFERENCES:

1. Telis provides regulatory update on TLX101-CDx. News release. Telix Pharmaceuticals. May 1, 2025. Accessed May 8, 2025. https://tinyurl.com/4dmb647b

2. FDA accepts new drug application and grants priority review for TLX101-CDx (Pixclara®) brain cancer imaging agent. News release. Telix Precision Medicine. October 24, 2024. Accessed March 11, 2025. https://tinyurl.com/4a2hf4mj

3. 131I-TLX-101 for treatment of newly diagnosed glioblastoma (IPAX-2). ClinicalTrials.gov. Updated July 19, 2023. Accessed March 11, 2025. https://clinicaltrials.gov/study/NCT05450744

4. An open label, single arm monocentric phase II study to evaluate safety, tolerability, and preliminary efficacy of carrier-added 4-L- [131I]iodophenylalanine (131I-IPA), administered as sequential injections in patients with recurrent IDH1/2 high grade glioma (HGG) concomitantly to 2nd line external radiation therapy. EU Clinical Trials Register. January 10, 2022. Accessed March 11, 2025. https://tinyurl.com/mvnubyf8