AMXT 1501 Plus Difluoromethylornithine Nets FDA Orphan Drug Designation in Neuroblastoma

The novel polyamine transport inhibitor AMXT 1501 has received orphan drug designation from the FDA for use in combination with difluoromethylornithine (Iwilfin) for the treatment of patients with neuroblastoma.1

AMXT 1501 is designed to block the uptake of polyamines, which are key for tumor growth and survival. When combined with difluoromethylornithine, AMXT 1501 is intended to comprehensively suppress polyamine metabolism. This pathway has been shown to be crucial in the development, metastasis, and resistance to treatment of neuroblastoma and other cancers. The combination of AMXT 1501 and difluoromethylornithine will be examined for the treatment of patients with neuroblastoma, central nervous system (CNS) tumors, and sarcomas in a phase 1/2 clinical trial (NCT06465199).2

“Receiving orphan drug designation for AMXT 1501 in combination with difluoromethylornithine represents an important milestone in our mission to develop innovative therapies for children with life-threatening cancers,” Mark Burns, PhD, the chief scientific officer and president of Aminex Therapeutics, stated in a news release.1 “We are committed to working closely with regulators, investigators and patient advocacy groups, to accelerate the clinical development efforts for AMXT 1501 in combination with difluoromethylornithine for the treatment of [patients with] neuroblastoma and other childhood and adult tumor types in collaboration with the Beat Childhood Cancer Research Consortium.”

Burns is also a professor of neuroscience at Georgetown University in Washington DC.

What Is the Regulatory History of Difluoromethylornithine in Neuroblastoma?

In December 2023, difluoromethylornithine was approved by the FDA to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who experienced at least a partial response to prior multi-agent, multimodality therapy including anti-GD2 immunotherapy.3

The approval was supported by data froman externally controlled trial which compared outcomes from the phase 2 Study 3b (NCT02395666; investigational arm) and Study ANBL0032 (clinical trial–derived external control arm). Findings from the protocol-specified primary analysis revealed that the HR for event-free survival (EFS) was 0.48 (95% CI, 0.27-0.85) and the HR for overall survival (OS) was 0.32 (95% CI, 0.15-0.70). Moreover, findings from supplementary analyses in subpopulations or via alternative statistical methods, which were conducted due to the externally controlled study design, showed that the HR for EFS ranged from 0.43 (95% CI, 0.23-0.79) to 0.59 (95% CI, 0.28-1.27), and the HRfor OS ranged from 0.29 (95% CI, 0.11-0.72) to 0.45 (95% CI, 0.21-0.98).

In terms of safety, adverse effects (AEs) that occurred in at least 5% of patients in Study 3b included otitis media, diarrhea, cough, sinusitis, pneumonia, and upper respiratory tract infection.

What Are the Key Design Characteristics of the Phase 1/2 Study?

The phase 1/2 study of difluoromethylornithine plus AMXT 1501 will include a dose escalation portion using the combination followed by a randomized controlled trial of difluoromethylornithine, with or without AMXT 1501, in patients with neuroblastoma, CNS tumors, and sarcomas.2 The phase 1 portion of the study will include an adolescent and young adult (AYA) cohort that will enroll patients who are at least 12 years old, as well as a pediatric cohort of patients less than 12 years of age at enrollment who may only be included after review from the data and safety monitoring board confirms the recommended phase 2 dose (RP2D). Phase 2 will include patients 21 years old or younger at diagnosis; 2 separate age-specific RP2Ds may be tested in this cohort.

Additional inclusion criteria will include a confirmed pathologic diagnosis of relapsed/refractory neuroblastoma, embryonal tumor with multilayer rosettes, atypical teratoid rhabdoid tumor, diffuse intrinsic pontine glioma, Ewing sarcoma, or osteosarcoma. Eligible patients will also be required to have fully recovered from the acute toxic effects of all prior anticancer chemotherapy, have a Lansky or Karnofsky Performance Scale score of a least 60, and adequate renal function.

In phase 1, the AYA and pediatric cohorts will follow a standard 3+3 design. Patients will receive up to twenty-four 28-day cycles of AMXT 1501 plus difluoromethylornithine. Oral AMXT 1501 will be administered at a starting dose of 350 mg/m2 twice daily.

In phase 2, patients will be randomly assigned to receive either AMXT 1501 plus difluoromethylornithine, both at the RP2D, or difluoromethylornithine monotherapy. In this phase, patients will also receive up to twenty-four 28-day cycles of their designated treatment.

The primary outcome in phase 1 is safety and tolerability measured by the number of patients with AEs. The primary outcome in phase 2 is progression-free survival (PFS). The secondary outcomes in phase 1 are PFS and overall response rate (ORR). In phase 2, secondary outcomes include ORR, OS, and safety and tolerability.

As of September 10, 2025, the study is not yet recruiting patients. It will enroll an estimated 289 patients and has an estimated primary completion date of February 2033.

“Neuroblastoma is a rare childhood cancer that unfortunately, accounts for 12% [to] 15% of all pediatric cancer deaths in the United States,” Giselle Sholler, MD, the chief of the Division of Pediatric Hematology/Oncology at Penn State Health Children’s Hospital, as well as the director of pediatric oncology research and a professor of pediatrics and neuroscience at Penn State College of Medicine, in Hershey, Pennsylvania, added in the news release.1 “We believe this combination has the potential to build upon the FDA approval of difluoromethylornithine to further improve clinical outcomes for children with neuroblastoma and other rare childhood cancers.”

References

1. Aminex therapeutics announces FDA orphan drug designation granted to AMXT 1501 in combination with DFMO for the treatment of neuroblastoma. News release. Aminex Therapeutics. October 2, 2025. Accessed October 2, 2025. https://aminextx.com/wp-content/uploads/2025/10/Aminex-ODD-Press-Release-Final-10_2_25.pdf
2. Eflornithine (DFMO) and AMXT 1501 for neuroblastoma, CNS tumors, and sarcomas. ClinicalTrials.gov. Updated September 10, 2025. Accessed October 2, 2025. https://clinicaltrials.gov/study/NCT06465199
3. FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma. FDA. Updated December 14, 2023. Accessed October 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-eflornithine-adult-and-pediatric-patients-high-risk-neuroblastoma?utm_medium=email&utm_source=govdelivery