On December 13, 2023, eflornithine (Iwilfin), an ornithine decarboxylase inhibitor, was approved for adult and pediatric patients with high-risk neuroblastoma with at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy.¹

This represents the first U.S. Food and Drug Administration approval of a therapy intended to reduce the risk of relapse in pediatric patients with high-risk neuroblastoma.

Supporting Efficacy Data

Approval was based on findings in Study 3b (ClinicalTrials.gov identifier NCT02395666) compared with an external control group from Study ANBL0032. The primary analysis consisted of 1:3 propensity score matching of 90 patients from Study 3b and 270 from ANBL0032 with comparison of event-free survival. Patients in Study 3b received eflornithine twice daily at a dosage based on body surface area until disease progression or unacceptable toxicity, or a maximum of 2 years. Patients with high-risk neuroblastoma in ANBL0032 received dinutuximab, granulocyte-macrophage colony-stimulating factor, interleukin-2, and cis-retinoic acid vs cis-retinoic acid alone. Patients in the primary analysis had median age at diagnosis of 3 years (range = 0.1–20.1 years).

The hazard ratio for event-free survival was 0.48 (95% confidence interval [CI] = 0.27–0.85) for the eflornithine vs control group. The hazard ratio for overall survival was 0.32 (95% CI = 0.15–0.70).

How It Is Used

The recommended dose is based on body surface area—ie, 768 mg twice daily, 576 twice daily, 384 twice daily, and 192 twice daily for > 1.5 m², 0.75 to 1.5 m², 0.5 to < 0.75 m², and 0.25 to < 0.50 m², respectively. Product labeling provides instruction on dosage modification for adverse reactions.

Safety Profile

The most common adverse events of any grade among 85 patients receiving eflornithine in Study 3 were otitis media (32%), diarrhea (15%), cough (15%), sinusitis (13%), and pneumonia (12%). The most common grade 3 adverse events included hearing loss (7%) and skin infection (4.7%). The most common grade 3 or 4 laboratory abnormalities were decreased neutrophils (8%), increased alanine aminotransferase (7%), and increase aspartate aminotransferase (6%).

Eflornithine has warnings/precautions for myelosuppression, hepatotoxicity, hearing loss, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving eflornithine. 

REFERENCE

1. Iwilfin (eflornithine) tablets, for oral use, prescribing information, USWM, LLC, December 2023. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2023/215500s000lbl.pdf. Accessed December 20, 2023.