EU Approval Is Sought for Eflornithine in High-Risk Neuroblastoma

Neuroblastoma | Sebastian Kaulitzki – stock.adobe.com

A marketing authorization application has been submitted to the European Medicines Agency (EMA) seeking the approval of eflornithine (difluoromethylornithine; Iwilfin) for the treatment of patients with high-risk neuroblastoma (HRNB).¹

“This submission via the European Union Centralized Procedure represents another important step in the regulatory process for eflornithine and further emphasizes Norgine’s passion and commitment in attempting to secure additional treatment options for patients living with high-risk neuroblastoma, a condition with a high level of unmet medical need,” David Gillen, MBBS, chief medical officer at Norgine, stated in a news release.

Previously, in 2023, the FDA approved eflornithine as oral maintenance therapy to reduce the risk of relapse in adult and pediatric patients with HRNB who have attained a partial response or better with prior multi-agent, multimodality therapy, including GD2-directed immunotherapy.² This regulatory decision was supported by findings from a study comparing outcomes of patients with HRNB treated with post-immunotherapy eflornithine from Study 3b/NMTRC003B (NCT02395666) vs patients with HRNB from Study ANBL0032 (NCT00026312) who received post-consolidation immunotherapy and did not subsequently receive eflornithine, comprising the comparative study’s clinical trial–derived external control arm.

This propensity score–matched analysis showed that treatment with eflornithine after the completion of immunotherapy resulted in improved event-free survival (EFS; HR, 0.496; 95% CI, 0.294-0.835; P = .0083) and overall survival (OS; HR, 0.376; 95% CI, 0.185-0.764; P = .0069) outcomes vs treatment with standard-of-care (SOC) therapy.³ The estimated 4-year EFS rates were 84% (standard error [SE], ±4%) and 72% (SE, ±2%) in the eflornithine-treated and –non-treated groups, respectively. The estimated 4-year OS rates were 96% (SE, ±2%) and 84% (SE, ±1%) in these respective groups.

Study ANBL0032 enrolled patients with post-consolidation HRNB who were randomly assigned to receive treatment with SOC 13-cis-Retinoic acid (RA) with or without dinutuximab (Unituxin). Based on meaningful improvements observed regarding 2-year EFS in patients who received dinutuximab plus RA vs RA alone, a single-arm continuation of ANBL0032 was initiated that established dinutuximab plus RA as standard post-consolidation therapy for patients with HRNB. Among patients who received dinutuximab plus RA, the 2-year EFS from standard immunotherapy was 66% (±5%); however, this rate declined to 56.6% (±4.7%) at 5 years.

The intent-to-treat population of the single-arm Study 3b enrolled 140 patients with HRNB who had received standard frontline or relapsed/refractory disease treatment. Patients received a maximum of 2 years of continuous treatment with oral eflornithine at 750 (±250) mg/m² twice daily. This trial showed that treatment with eflornithine elicited a 2-year EFS rate of 85%.

The comparative study included 92 patients from Study 3b who received treatment consistent with that given to the eflornithine-treated patients in Study ANBL0032, including 87 patients with confirmed prior participation in ANBL0032. The study also included 852 control patients from ANBL0032 who were eligible for enrollment in Study 3b following immunotherapy but did not enroll.

In April 2024, applications seeking the approval of this agent for this indication were submitted in Australia, Switzerland, and the United Kingdom.¹

“Submitting this marketing authorization to the EMA marks a pivotal step for patients facing this challenging cancer,” Janneke van der Kamp, chief executive officer of Norgine, concluded in the news release. “We are committed to advancing innovative therapies that address the unmet needs of young patients and their families, and this milestone brings us closer to offering hope where it’s most needed.”

References

1. Norgine submits marketing authorisation application to the European Medicines Agency for eflornithine (difluoromethylornithine [DFMO]) in high-risk neuroblastoma. News Release. Norgine. January 7, 2025. Accessed January 7, 2025. https://norgine.com/press_release/norgine-submits-marketing-authorisation-application-to-the-european-medicines-agency-for-eflornithine-difluoromethylornithine-dfmo-in-high-risk-neuroblastoma/
2. FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma. FDA. December 13, 2023. Accessed January 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-eflornithine-adult-and-pediatric-patients-high-risk-neuroblastoma
3. Oesterheld J, Ferguson W, Kraveka JM, et al. Eflornithine as postimmunotherapy maintenance in high-risk neuroblastoma: externally controlled, propensity score-matched survival outcome comparisons. J Clin Oncol. 2024;42(1):90-102. doi:10.1200/JCO.22.02875