AGuIX Receives FDA Fast Track Designation in Glioblastoma

The FDA has granted fast track designation to AGuIX for the treatment of patients with malignant gliomas and glioblastoma.¹

“We are delighted to have received this FDA fast track designation for AGuIX in the treatment of [patients with] malignant glioma,” Vincent Carrère, chief executive officer of NH TherAguix stated in a press release. “It demonstrates the strong interest of the US regulatory authorities in our next-generation radio-enhancer. We are convinced that AGuIX holds great potential to offer an effective clinical and therapeutic response to patients suffering from these deadly cancers, for whom existing treatments remain largely insufficient. 2024 should be a major turning point in the development of our promising nano-drug, and we look forward to sharing the first results from our clinical trials later this year.”

AGuIX is a nanodrug mostly comprised of gadolinium that offers strong contrast imaging properties and potentially indirectly increases the delivered dose of radiation. The agent allows for precise tumor delineation with MRI and can improve the efficacy of radiotherapy. Additionally, AGuIX has a tolerable safety profile.

Findings from the first-in-human study of AGuIX, the phase 1b NANO-RAD-1 trial (NCT02820454), demonstrated that patients with multiple brain metastases who received the agent in combination with whole brain radiotherapy (n = 15) experienced T1 MRI enhancement with tumor selectivity and persistence of AGuIX contrast enhancement in patients with primary melanoma, lung, breast, and colon cancers. Additionally, among evaluable patients (n = 14), 13 achieved a clinical benefit and MRI analysis displayed a significant association between contrast enhancement and tumor response, providing evidence for the radiosensitizing effect of AGuIX. The median intracranial progression-free survival was 5.5 months, and the median overall survival was 5.5 months.²

In terms of safety, no dose-limiting toxicities were reported and the maximum-tolerated dose was not determined. Four serious adverse effects (AEs) occurred. Acute grade 1 or 2 AEs included headache (40%), nausea (33.3%), increased intracranial pressure (20%), paresthesia (20%), and confusion (20%). Grade 3 acute AEs were increased intracranial pressure (6.7%), partial seizures (6.7%), and blindness (6.7%); there were no grade 4 events. Ten patients died during study follow-up and 9 of these deaths were considered by investigators to be unrelated to investigational treatment.

AGuIX is also under evaluation in 3 phase 2 clinical trials that are expected to provide data updates in the second half of 2024: NANORAD2 (NCT03818386), NANO-GBM (NCT04881032), and NANOBRAINMETS (NCT04899908). NANORAD2 is enrolling approximately 100 patients with brain metastases and is evaluating the agent in combination with whole brain radiotherapy; NANO-GBM is examining AGuIX in approximately 62 patients with glioblastoma; and NANOBRAINMETS is evaluating AGuIX in combination with stereotactic radiotherapy in approximately 134 patients with brain metastases. Recruitment to NANORAD2 has been finalized and the interim efficacy findings are expected by the end of 2024; the interim efficacy analysis of NANO-GBM is anticipated by the end of 2024; and initial findings from an interim efficacy analysis of NANOBRAINMETS are expected in November 2024.1

“Glioblastoma [is] the most common type of malignant primary brain tumor and accounts for most deaths among patients with primary tumors,” Olivier de Beaumont, CMO of NH TherAguix, said in the press release. “Although there has been progresses in understanding the biology of these tumors, the unmet therapeutic need remains very important. This fast track designation will facilitate NH TherAguix more frequent interactions with the FDA as well as accelerated approval and priority review in glioblastoma indications. This program will be led in parallel to our ongoing clinical development program in brain metastases, where [a] preliminary signal of efficacy of AGuIX has already been detected.”

References

• NH TherAguix receives FDA fast track designation. News release. NH TherAguix. May 30, 2024. Accessed May 30, 2024. https://www.globenewswire.com/news-release/2024/05/30/2890749/0/en/NH-TherAguix-receives-FDA-Fast-Track-designation.html
• Verry C, Dufort S, Villa J, et al. Theranostic AGuIX nanoparticles as radiosensitizer: a phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial). Radiother Oncol. 2021;160:159-165. doi:10.1016/j.radonc.2021.04.021