FDA grants fast track designation to 225Ac-FL-020 in mCRPC

The FDA has awarded a fast track designation to ²²⁵Ac-FL-020, an investigational PSMA-targeting radionuclide drug conjugate for the potential treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), announced Full-Life Technologies, the developer of the therapy, in a news release.¹

225Ac-FL-020 is an actinium-225 (225Ac)-based PSMA radioligand therapy designed to selectively attack cancer cells.

Fast track designation is awarded to new drugs and vaccines that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. With this designation, the development process for ²²⁵Ac-FL-020 can benefit from more frequent engagement with the FDA, eligibility for accelerated approval, and priority review.

"The FDA Fast Track Designation for ²²⁵Ac-FL-020 underscores the critical need for innovative and effective treatments for mCRPC", said Steffen Heeger, MD, MSc, chief medical officer of Full-Life Technologies, in the news release.¹ "This designation will enable us to collaborate more closely with the FDA throughout the development process, potentially accelerating the availability of ²²⁵Ac-FL-020 to patients."

In May 2024, the FDA cleared an investigational new drug application for ²²⁵Ac-FL-020 to initiate clinical trials of the therapy in the US and globally in patients with prostate cancer.² The phase 1 clinical trial of the therapy, which was set to launch this year, will assess the safety, tolerability, and preliminary anti-tumor activity of ²²⁵Ac-FL-020 in patients with mCRPC.

²²⁵Ac-FL-020 is an actinium-225 (²²⁵Ac)-based PSMA radioligand therapy designed to selectively attack cancer cells. Preclinical data on the therapy were presented earlier this year at the 2024 Annual Meeting of the American Association for Cancer Research in San Diego, California.³

The preclinical study first assessed the binding affinity of the non-labeled vector FL-020 against PSMA in vitro, showing that FL-020 bound to LNCaP cells with an IC₅₀ value of 51.55 nM. The authors also noted high and sustained tumor uptake and fast systemic clearance with Indium-111 (¹¹¹In)-FL-020 in PSMA high LNCaP tumor-bearing nude mice.

Further, the study indicated high selectivity of FL-020, with off-target screening showing that less than 50% of inhibition of binding or activity was observed by FL-020 at 10 µM against 85 targets, including receptors, ions, channels, enzymes, and transporters.

The investigators also compared the anti-tumor activity of ²²⁵Ac-FL-020 in LNCaP xenograft models to that of ²²⁵Ac-PSMA-617. Findings showed that ²²⁵Ac-FL-020 demonstrated superior anti-tumor activity to ²²⁵Ac-PSMA-617 at the dose level of 10 KBq/mouse in the LNCaP xenograft model. Additionally, the therapy had a favorable safety profile as indicated by body weight and hematological parameters.

Based on these data, the authors concluded,³ “Taken together, these results collectively demonstrate that ²²⁵Ac-FL-020 is a potent and selective PSMA-targeting radioligand therapy candidate with superior anti-tumor activity and a favorable safety profile warranting further clinical development.”

References

1. Full-Life Technologies granted FDA fast track designation for 225Ac-FL-020 for the treatment of metastatic castration-resistant prostate cancer. News release. Full-Life Technologies. July 2, 2024. Accessed July 3, 2024. https://www.full-life.com/media/press-releases/27

2. Full-Life Technologies announces clearance from FDA of IND application for 225Ac-FL-020 for the treatment of metastatic castration-resistant prostate cancer. News release. Full-Life Technologies. May 30, 2024. Accessed July 3, 2024. https://www.full-life.com/media/press-releases/24

3. Liu F, Zhang J, Yang J, et al. 225Ac-FL-020 is a novel PSMA-targeting radionuclide drug conjugate (RDC) with superior in vivo anti-tumor activity. Presented at: 2024 Annual Meeting of the American Association for Cancer Research (AACR). April 5-10, 2024. San Diego, California. Abstract 6023