FDA Grants Orphan Drug Designation to 225Ac-Satoreotide for SCLC

The FDA has granted orphan drug designation to the systemic radiopharmaceutical 225Ac-satoreotide (SSO110) as a potential therapeutic option for patients with small cell lung cancer (SCLC).1

Satoreotide is a SSTR2 antagonist labelled with lutetium-177 (177Lu) or actinium-255 (225Ac). Overexpression of the SSTR2 receptor can be found in aggressive neuroendocrine tumors (NETs) such as SCLC or Merkel cell carcinoma (MCC).

The agent is being developed in tandem with 68Ga-SSO120, which is a companion patient selection tracer, with the goal of combining the pair for the diagnosis and targeted radionuclide treatment of patients with malignancies known to express SSTR2, including SCLC, MCC, and other aggressive, hard-to-treat cancers.

“Receiving orphan drug designation for 225Ac-satoreotide is a recognition of its potential as a treatment option for patients with SCLC and an important regulatory milestone for Ariceum,” Manfred Rüdiger, chief executive officer at Ariceum Therapeutics, stated in a news release. “The FDA’s orphan drug designation will support our objective to accelerate the development of satoreotide through human trials to provide a potentially life-saving therapy to patients with limited alternatives.”

In January 2025, Ariceum Therapeutics announced that the FDA cleared an investigational new drug application for the phase 1/2 SANTANA-225 trial, which will evaluate 225Ac-satoreotide in patients with SCLC or MCC.2

The global, open-label study will examine the safety, tolerability, preliminary efficacy, and recommended phase 2 dose of 225Ac-satoreotide in patients with extensive-stage SCLC or MCC who are on first-line maintenance therapy with checkpoint inhibitors. The trial is expected to begin recruiting patients in the first quarter of 2025.

“[Clearance of the SANTANA-225 trial] is an important milestone, not only for Ariceum but for the whole field of targeted radionuclide cancer treatments,” Germo Gericke, chief medical officer at Ariceum Therapeutics, stated in a news release.2 “225Ac-[satoreotide] is the first SSTR2 antagonist labelled with actinium-225 to undergo human trials, providing the optimum combination of a long half-life α particle emitter with a long tumor retention tracer. Based on encouraging clinical data with 177Lu-[satoreotide] and very promising preclinical data of 225Ac-[satoreotide], we are very optimistic about the potential for patients with difficult to treat cancers.”

Preclinical data presented at the 2024 European Association of Nuclear Medicine Annual Meeting demonstrated that satoreotide produced a higher preclinical antitumor activity compared with DOTA-TATE, irrespective of the radionucleotide used.3 Among the different radionucleotides evaluated between satoreotide and DOTA-TATE, 225Ac-satoreotide generated the strongest antitumor effect in vivo at a low, single dose. The DOTA-TATE–based agents were less potent and required increased dose levels.

225Ac-satoreotide was also shown to be multiple times more potent than 225Ac-DOTA-TATE, as evidenced by a durable complete response in standard murine xenograft models of SCLC in animal models.

“These results provide strong evidence for satoreotide and its potential to clinically outperform SSTR2 targeting agonists, by demonstrating significantly better efficacy in tumor growth control, up to complete tumor eradication depending on isotope used,” Rüdiger stated in another news release.3 “In addition, when a single dose of 30 kBq 225Ac-satoreotide was administered, we observed high frequency of complete durable responses and 100% survival which strongly supports further clinical development for the treatment of SCLC, MCC, and other cancers.”

References

1. U.S. FDA grants orphan drug designation to Ariceum Therapeutics’ proprietary radiopharmaceutical cancer therapy. News release. Ariceum Therapeutics. February 6, 2025. Accessed February 6, 2025. https://ariceum-therapeutics.com/u-s-fda-grants-orphan-drug-designation-to-ariceum-therapeutics-proprietary-radiopharmaceutical-cancer-therapy/
2. FDA Ccears Ariceum Therapeutics’ 225Ac-satoreotide phase I/II clinical study in patients with small cell lung cancer or Merkel cell carcinoma. News release. Ariceum Therapeutics. January 14, 2025. Accessed February 6, 2025. https://ariceum-therapeutics.com/fda-clears-ariceum-therapeutics-225ac-satoreotide-phase-i-ii-clinical-study-in-patients-with-small-cell-lung-cancer-or-merkel-cell-carcinoma/
3. Ariceum Therapeutics presents outstanding data on its first-in-class radiopharmaceutical drug 225Ac-satoreotide at the European Association of Nuclear Medicine 2024. News release. Ariceum Therapeutics. October 22, 2024. Accessed February 6, 2025. https://ariceum-therapeutics.com/ariceum-therapeutics-presents-outstanding-data-on-its-first-in-class-radiopharmaceutical-drug-225ac-satoreotide-at-the-european-association-of-nuclear-medicine-2024/