FDA Receives NDA Resubmission for 18F-FET PET Imaging Agent in Recurrent Glioma

A new drug application (NDA) has been submitted to the FDA for TLX101-Px (Pixclara; ¹⁸F-FET) for the characterization of progressive or recurrent glioma from treatment related changes in adult and pediatric patients, according to an announcement from Telix Pharmaceuticals.¹ The company indicated that the updated filing included a comprehensive data set and new statistical analyses derived from existing clinical studies, as agreed upon during a Type A meeting with the FDA.

The NDA resubmission follows a complete response letter (CRL) issued by the agency in April 2025, which requested additional confirmatory clinical evidence regarding the agent’s diagnostic performance.² Prior to the CRL, TLX101-Px received orphan drug designation in October 2020, and fast track designation in April 2024.^3,4

“We appreciate the FDA’s recognition of the critical unmet need to improve the diagnosis and management of glioma, particularly in the post-treatment setting. Our resubmission is supported by an extensive and compelling data set – particularly so for an orphan indication,” said David N. Cade, chief medical officer of Telix Group, in the press release.¹ “We are grateful to our global clinical collaborators, who share our commitment to ensuring patients in the US can benefit from this important patient management tool.”

The clinical utility of TLX101-Px is rooted in its ability to target the Large Amino Acid Transporters 1 and 2 (LAT1/LAT2), which are significantly upregulated in neoplastic brain tissue. Unlike standard ¹⁸F-fluorodeoxyglucose (FDG) PET, which is hampered by high physiological background uptake in the brain, ¹⁸F-FET exhibits minimal accumulation in healthy gray matter, resulting in a high tumor-to-background contrast.⁵

Meta-analyses of TLX101-Px diagnostic performance have demonstrated a pooled sensitivity of approximately 0.88 (95% CI, 0.80-0.93) and a specificity of 0.78 (95% CI, 0.69-0.85) for differentiating true progression from post-treatment-related changes.⁶ In comparison, conventional contrast-enhanced MRI often yields equivocal results in the post-treatment setting because gadolinium enhancement is a non-specific marker of blood-brain barrier disruption rather than a direct indicator of metabolic tumor activity. Independent studies have shown that TLX101-Px can detect tumor infiltration up to 1 cm beyond the margins of MRI-defined contrast enhancement, potentially facilitating more precise radiotherapy planning and surgical resection.^7,8

Community advocates have highlighted the importance of expedited access. Maggie Haynes, executive director of the Head for the Cure Foundation, expressed hope for an expedited review, “Our community is encouraged by the FDA’s ongoing engagement and guidance to the sponsor and support for the Expanded Access Program for TLX101-Px. We are hopeful of an expedited review, so this important and proven imaging option can become available to those who urgently need it.”

Results from the phase 1 IPAX-2 (NCT05450744) and phase 2 IPAX-Linz trials supported the initial NDA campaigning for TLX101-Px’s regulatory success.

In the phase 1 IPAX-2 trial, the safety of ascending doses of ¹⁸F-FET administered intravenously as an injection or solution was evaluated.⁹ The primary outcomes were the incidence and grade of dose-limiting toxicities, as well as safety, tolerability, and recommended phase 2 dose.

Eligible patients were 18 years or older with histologically confirmed intracranial glioblastoma following surgical resection, who had prior surgery but no systemic therapy or radiation therapy for glioblastoma. A plan to begin chemoradiation 3 to 6 weeks after surgical resection, Karnofsky performance status of 70 or greater, and adequate organ function were additional enrollment criteria.

References

1. Telix resubmits NDA to U.S. FDA for TLX101-Px (Pixclara®) brain cancer imaging candidate. Telix Pharmaceuticals. Published March 16, 2026. Accessed March 16, 2026. https://tinyurl.com/43sts63h
2. Telix provides regulatory update on TLX101-CDx. News release. Telix Pharmaceuticals Limited. April 28, 2025. Accessed March 16, 2026. https://tinyurl.com/4nf5fesa
3. Telix granted FDA orphan drug designation for glioma imaging agent. News release. Telix Pharmaceuticals. October 6, 2020. Accessed March 16, 2026. https://tinyurl.com/muhzdf2x
4. TLX101-CDx (Pixclara™) granted FDA fast track designation. News release. Telix Pharmaceuticals Limited. April 15, 2024. Accessed March 16, 2026. https://tinyurl.com/2fu33ryy
5. Langen KJ, Galldiks N, Casneuf T, et al. Imaging of amino acid transport in brain tumors: 18F-FET PET. J Nucl Med. 2017;58(12):1900-1906. https://jnm.snmjournals.org/content/58/12/1900
6. Cui M, Zorrilla-Veloz RI, Hu J, Guan B, Ma X. Diagnostic accuracy of PET for differentiating true glioma progression from post treatment-related changes: A systematic review and meta-analysis. Front Neurol. 2021;12:671867. Published 2021 May 20. doi:10.3389/fneur.2021.671867
7. Galldiks N, Lommers E, Holy R, et al. Diagnosis of tumor progression and treatment-related changes in glioma patients using amino acid PET: The EANO/RANO practice guidelines. Neuro-Oncol. 2019;21(11):1431-1440. https://doi.org/10.1093/neuonc/noz130
8. Everard A, Versnel D, Ruijters V, et al. Comparison of ¹⁸F-FET-PET- and MRI-based target definition for re-irradiation treatment of recurrent diffuse glioma. Clin Transl Radiat Oncol. 2025;52:100931. Published 2025 Feb 11. doi:10.1016/j.ctro.2025.100931
9. 131I-TLX-101 for treatment of newly diagnosed glioblastoma (IPAX-2) (IPAX-2). ClinicalTrials.gov. Updated January 21, 2026. Accessed March 16, 2026. https://tinyurl.com/vvrvve2b