The FDA has accepted the new drug application (NDA) and granted priority review to TLX101-CDx (18F-floretyrosine or 18F-FET; Pixclara) for glioma imaging. The FDA’s decision is anticipated by April 26, 2025, under the Prescription Drug User Fee Act. This decision marks a significant step toward improving brain cancer imaging in the United States.
Addressing Unmet Needs in Glioma Imaging
Currently, there are no approved targeted amino acid PET agents in the US for adult and pediatric brain cancer imaging. This leaves patients and providers reliant on conventional MRI, which has limitations such as a lack of biological specificity and an inability to distinguish between disease progression and treatment-related effects. TLX101-CDx aims to address these limitations by targeting the membrane transport proteins LAT1 and LAT2.
According to Telix Precision Medicine CEO Kevin Richardson, FDA approval of TLX101-CDx would significantly advance brain cancer imaging in the U.S., aligning it with the standards used in other markets. He emphasized the critical need for better imaging in brain cancer and Telix's commitment to delivering precision medicine solutions.
TLX101-CDx and TLX101-Tx: A Potential Theranostic Approach
18F-FET is a PET agent designed to characterize treatment-related changes in both adult and pediatric patients with progressive or recurrent glioma. It is already included in international clinical practice guidelines for glioma imaging. Furthermore, 18F-FET may be developed as a companion diagnostic agent for TLX101-Tx (131I-iodofalan; 131I-IPA), an investigational LAT1-directed neuro-oncology drug. TLX101-Tx targets the same amino acid transporter mechanism with therapeutic targeted radiation.
Ongoing Clinical Trials of TLX101-Tx
131I-IPA is currently being evaluated in several clinical trials:
- IPAX-2 (NCT05450744): 131I-IPA in combination with the best standard of care for newly diagnosed glioblastoma.
- IPAX-Linz-01 (EudraCT2021-006426-43): 131I-IPA in combination with concomitant external radiation therapy for recurrent IDH1/2-mutated high-grade glioma.
IPAX-1 Trial Results
Earlier findings from the final analysis of the phase 1/2 IPAX-1 trial (NCT03849105) showed that 131I-IPA, combined with external beam radiation therapy, was safe and tolerable as a second-line therapy for patients with recurrent glioblastoma multiforme. The most common treatment-emergent adverse effects (TEAEs) included decreased lymphocyte count, fatigue, headache, and hiccups. Preliminary efficacy data indicated a median overall survival of 13 months from the start of treatment in the recurrent setting and 23 months from initial diagnosis. These results suggest a potential benefit in using 131I-IPA in treating recurrent glioblastoma.
