Orphan Drug Designation Granted to 225Ac-SSO110 for SCLC

Following promising results from a trial investigating the effects of ²²⁵Ac-SSO110 on Balb/c nude mice injected with the xenograft model of SCLC, IND clearance was granted by the FDA.

²²⁵Ac-SSO110 (satoreotide), a first-in-class actinium-labelled somatostatin receptor 2 antagonist, was granted orphan drug designation from the FDA for the treatment of patients with small cell lung cancer (SCLC), according to a press release from the developer, Ariceum Therapeutics.¹

The developer plans to begin phase 1/2 human clinical development of satoreotide in the SANTANA-225 trial in the first quarter of 2025 that will investigate the agent in patients with SCLC or Merkel cell carcinoma.²

Preclinical results presented at the 2024 European Association of Nuclear Medicine Annual Conference in Hamburg, Germany demonstrated the significant potential of satoreotide.³ The aim of the study was to identify the optimal isotope for SSO110; options included ²²⁵Ac, ²¹²Pb, ¹⁶¹Pb, and ¹⁷⁷Lu. Anti-tumor efficacy data of ¹⁷⁷Lu-SSO110 and ²²⁵Ac-SSO110 to ²²⁵Ac-DOTA-Tate

“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, wrote in the press release.¹ “The FDA’s orphan drug designation will support our objective to accelerate the development of 225Ac-satoreotide through human trials to provide a potentially life-saving therapy to patients with limited alternatives.”

²²⁵Ac and ²¹²Pb-labeled satoreotide elicited a tumor uptake of 10.3% ID/g and 4.7% ID/g, respectively, at 4 hours. The regions with the highest levels of normal tissue uptake were kidneys (13.9% ID/g vs 10.5% ID/g, respectively), pancreas (1.2% ID/g vs 0.9% ID/g, respectively), and stomach (1.3% ID/g vs 0.6% ID/g, respectively).

From 4 hours to 96 hours, ²²⁵Ac-sanreotide’s tumor-to-kidney ratios increased from .75 to 1.4, demonstrating clearance from the kidney while being retained in the tumor.

Tumor growth inhibition was observed in all treatment groups aside from the 3.3 kBq ²²⁵Ac-sanreotide group; 30 kBq ²²⁵Ac-sanreotide and 20 MBq ¹⁷⁷Lu-sanreotide given in single-dose demonstrated superior tumor volume reductions compared with 30 kBq ²²⁵Ac-DOTA-TATE; and injection of only ²²⁵Ac-sanreotide elicited durable complete responses and 100% survival of treated mice in the NCI-H69 model.

In the trial, balb/c nude nude mice were engrafted with the xenograft model for SCLC, SSTR2–positive NCI-H69 tumor cells, and mice were randomized based on tumor volume before the start of treatment.

The tumor bearing mice (n = 4) were then injected with 90 kBq/1 µg of satoreotide and assessed for biodistribution in harvested organs and tissues at 4, 24, and 96 hours using liquid scintillation counting. Escalating single-doses of ²²⁵Ac-SSO110 were compared with ²²⁵Ac-DOTA-TATE, ¹⁷⁷Lu-SSO110, and vehicle; the average tumor volume at treatment initiation was 160 mm.³

Clinical signs and body weight changes were key end points monitored by investigators. Safety-relevant end points like organ weights and blood chemistry were also included at the end of the study.

“²²⁵Ac-SSO110 showed high tumor uptake and its biodistribution profile is highly similar to ¹⁷⁷LuSSO110 as expected. ²²⁵Ac-SSO110 was well tolerated,” lead study author Anika Jaekel, PhD, head of Translational Biology and Non-Clinical Pharmacology at Ariceum, and lead study author, wrote in the presentation.³ “These data warrant clinical investigation of ²²⁵Ac-SSO110 and a phase 1 clinical trial in patients with somatostatin receptor 2-positive is planned to start in Q1 of 2025.”

The developer hopes that “²²⁵Ac-SSO110 in tandem with ⁶⁸Ga-SSO120, a companion patient selection tracer, will operate as a “theranostic pair”.¹ The pair is intended to both diagnose and enact targeted radionuclide treatment of SSTR2-expressing, aggressive hard-to-treat cancers like SCLC and merkel cell carcinoma, among others.

Previously, the agent also received IND clearance from the FDA.

References

1. U.S. FDA grants orphan drug designation to Ariceum Therapeutics’ proprietary radiopharmaceutical cancer therapy. News release. Ariceum. February 6, 2025. Accessed February 6, 2025. https://tinyurl.com/326mc4wt
2. FDA clears Ariceum Therapeutics’ 225Ac-satoreotide phase I/II clinical study in patients with small cell lung cancer or merkel cell carcinoma. News release. Ariceum. January 14, 2025. Accessed February 6, 2025. https://tinyurl.com/vtkpvdwr
3. Jaekel A, Desai P, Sturzbecher-Hoehne M, et al. [²²⁵Ac]Ac-SSO110 and [¹⁷⁷Lu]Lu-SSO110 demonstrate significantly better efficacy than [²²⁵Ac]Ac-DOTA-TATE in the treatment of SSTR2-positive tumor xenografts. Presented at: 2024 European Association of Nuclear Medicine Annual Conference; October 19-23, 2024; Hamburg, Germany. Abstract 242038.