FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma

Regulatory approval: On Dec 13, 2023, the FDA approved eflornithine (IWILFIN; USWM, LLC) to reduce relapse risk in adult and pediatric patients with high-risk neuroblastoma who achieved at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. Approval was supported by an externally controlled comparison of Study 3b versus a propensity score–matched external control from ANBL0032, with EFS HR 0.48 and OS HR 0.32 in the primary analysis; uncertainty remains due to the study design.

FDA approval (Dec 13, 2023)

The FDA approved eflornithine (IWILFIN; USWM, LLC) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated ≥ partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. The agency noted this is the first FDA approval of a therapy intended to reduce relapse risk in pediatric HRNB.

Evidence base

Efficacy was evaluated in an externally controlled analysis comparing Study 3b (NCT02395666; multicenter, open-label, non-randomized) with an external control derived from Study ANBL0032.

  • In Study 3b, 105 eligible patients (Stratum 1) received oral eflornithine twice daily at a BSA-based dose until progression, unacceptable toxicity, or up to 2 years.
  • The external control came from 1,241 patients on the experimental arm of ANBL0032. Patients with complete covariate data were matched 1:3 by propensity scores for the primary analysis (90 IWILFIN vs 270 controls).

Primary analysis outcomes:

  • EFS (progression, relapse, secondary cancer, or death): HR 0.48 (95% CI, 0.27–0.85)
  • OS: HR 0.32 (95% CI, 0.15–0.70)

Because of uncertainty inherent to the external-control design, supplementary analyses showed EFS HR ranging 0.43–0.59 and OS HR 0.29–0.45, with some confidence intervals crossing 1.

Safety (≥5% in Study 3b)

Common adverse reactions/lab abnormalities included otitis media, diarrhea, cough, sinusitis, pneumonia, URTI, conjunctivitis, vomiting, pyrexia, allergic rhinitis, decreased neutrophils, increased ALT/AST, hearing loss, skin infection, and UTI.

The application used RTOR, and received priority review, breakthrough, and orphan drug designations.

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