FDA Sends CRL for PET Imaging Agent in Progressive/Recurrent Glioma

Previously, in October 2024, the FDA granted priority review to TLX101-CDx in recurrent glioma.

The FDA has issued a complete response letter (CRL) for TLX101-CDx (18F-floretyrosine; 18F-FET; Pixclara), a PET agent designed for the characterization of progressive or recurrent glioma in adult and pediatric patients, according to a press release from the developer, Telix Pharmaceuticals.1

The CRL highlighted that the FDA could not approve the new drug application (NDA) for TLX101-CDx in its current form, requiring additional confirmatory clinical evidence to progress the application. The agency did not describe any issues associated with the agent's safety.

Developers plan to organize a hearing with the FDA to review the basis of the agency's decision.

"We are committed to commercializing TLX101-CDx and fulfilling the unmet need to improve imaging to enable timelier and more accurate decisions for the clinical management of glioma," Christian Behrenbruch, DPhil, MBA, managing director and group chief executive officer at Telix, stated in the press release.1 "Our immediate focus is understanding the FDA’s feedback and augmenting our submission with additional data to satisfy the agency as soon as possible."

Previously, in October 2024, the FDA granted priority review to TLX101-CDx in recurrent glioma.2 In April 2024, the FDA granted fast track designation to the agent in recurrent glioma, and in October 2020, the FDA granted orphan drug designation to the agent in glioma.3,4

“Telix believes that the FDA approval of [TLX101-CDx] will drive a step-change for brain cancer imaging in the U.S., and bring it into line with a more advanced standard of care currently used in other markets,” Kevin Richardson, chief executive officer at Telix Precision Medicine, stated in the press release announcing priority review.2 “There is currently a critical need for better imaging in brain cancer, and Telix is dedicated to delivering precision medicine solutions that address patient needs and enhance both cancer imaging and treatment outcomes.”

Supporting results for the application came from the phase 1 IPAX-2 trial (NCT05450744) and the phase 2 IPAX-Linz trial.

IPAX-2 Trial

IPAX-2 is an open-label, single-arm, parallel-group phase 1 study evaluating TLX101-CDx plus standard of care in glioblastoma.

Eligible patients were between 18 and 65 years old with histologically confirmed intracranial glioblastoma following surgical resection who had prior surgery for their disease but no systemic therapy or radiation therapy.5 Additional inclusion criteria include a Karnofsky performance status of 70 or greater, adequate organ function at screening, agreement to begin chemoradiation therapy 3 to 6 weeks after surgical resection, and at least 6 slides without staining or a tissue block.

Those who had prior non-surgery treatment for glioma, unable to undergo contrast-enhanced MRI, intended to be treated with tumor-treating fields prior to progression, with haemostaseologic conditions precluding catheterization or invasive procedures, having phenylketonuria, and required chronic administration of high dose corticosteroids or other immunosuppressant drugs were excluded from participating in the trial.

“With IPAX-2, we are taking the development of TLX101 into front-line glioblastoma for the first time, and excited to see the potential impact of targeted radiation in patients after initial surgery,” Colin Hayward, MD, chief medical officer at Telix, stated in a press release.6

IPAX-Linz

IPAX-Linz was investigator-initiated and evaluated TLX101-CDx with external beam radiation therapy in the treatment of patients with recurrent high-grade gliomas.

The first patient was dosed in November 2022, and the trial is building on data generated in the phase 1/2 IPAX-1 trial (NCT03849105) that evaluated the safety, tolerability, dosing schedule, and preliminary efficacy of TLX101 therapy in patients with recurrent glioblastoma multiforme.

“Based on promising safety and early efficacy data for TLX101 in the IPAX-1 study, I am pleased to continue to explore this therapeutic modality in a larger patient cohort, where there are currently few effective treatment options,” Josef Pichler, of Kepler University Hospital in Austria and the principal investigator of the IPAX-Linz study, stated in a press release.7 “Preliminary results are only achieved thanks to close and optimal cooperation with our colleagues at Ordensklinikum Linz, Barmherzige Schwestern and we are grateful for their contribution to this trial.”

References

1. Telix provides regulatory update on TLX101-CDx. News release. Telix Pharmaceuticals Limited. April 28, 2025.
2. FDA accepts new drug application and grants priority review for TLX101CDx (Pixclara®) brain cancer imaging agent. News release. Telix Pharmaceuticals Limited. October 24, 2024. Accessed March 13, 2025. https://tinyurl.com/ytm76yaa
3. TLX101-CDx (Pixclara™) granted FDA fast track designation. News release. Telix Pharmaceuticals Limited. April 15, 2024. March 13, 2025. https://tinyurl.com/2fu33ryy
4. Telix granted FDA orphan drug designation for glioma imaging agent. News release. Telix Pharmaceuticals Limited. October 6, 2020. March 13, 2025. https://tinyurl.com/yhuptjzk
5. 131I-TLX-101 for treatment of newly diagnosed glioblastoma (IPAX-2) (IPAX-2). ClinicalTrials.gov. July 19, 2023. Accessed March 13, 2025. https://tinyurl.com/yc89c8pz
6. First patient dosed in IPAX-2 study of TLX101 brain cancer therapy candidate in patients with newly diagnosed glioblastoma. News release. Telix. August 8, 2023. Accessed March 14, 2025. https://tinyurl.com/y6t8nfnw
7. First patient dosed in phase II ‘IPAX-Linz’ study of TLX101 for glioblastoma therapy. News release. Telix. November 22, 2022. Accessed March 14, 2025. https://tinyurl.com/7sv3xcpz