USWM, LLC

• Norgine has submitted a marketing authorization application to the EMA for eflornithine to treat high-risk neuroblastoma (HRNB). • The application follows prior submissions in Australia, Switzerland, and the United Kingdom under Project Orbis. • Eflornithine is intended as an oral maintenance therapy to reduce relapse risk in pediatric and adult HRNB patients. • FDA approved eflornithine in December 2023 based on trials showing improved event-free and overall survival.

• Orbus Therapeutics' eflornithine combination with lomustine did not meet the primary endpoint of overall survival in the Phase III STELLAR trial for recurrent IDH mutant astrocytoma. • The combination therapy showed clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared to lomustine alone. • The STELLAR trial involved 343 patients and the combination therapy was well-tolerated, with common adverse events related to myelosuppression and hearing impairment. • Eflornithine, which blocks ornithine decarboxylase, previously received FDA orphan drug and breakthrough designations for anaplastic glioma.

• Eflornithine (DFMO) receives FDA approval for neuroblastoma treatment, marking a significant milestone in pediatric oncology. • Clinical trials show DFMO reduces relapse rates in neuroblastoma patients from 50% to 15% when used as maintenance therapy. • The development and trials of DFMO were largely funded by families of children affected by neuroblastoma, highlighting community support. • DFMO, initially an antiparasitic drug, has been found to suppress the MYCN gene, which drives neuroblastoma, offering a novel treatment approach.

• The FDA has approved eflornithine (Iwilfin) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB). • The approval is for patients who have achieved at least a partial response to prior multi-agent, multimodality therapy, including anti-GD2 immunotherapy. • Efficacy was demonstrated in an externally controlled trial, showing a significant improvement in event-free survival (EFS) and overall survival (OS). • Common adverse effects included otitis media, diarrhea, cough, and hearing loss, but the drug's manageable safety profile supported its approval.

• The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 14-6 in favor of eflornithine to reduce relapse risk in pediatric high-risk neuroblastoma patients. • The vote was based on data from Study 3b, a single-arm trial with an external control arm from the ANBL0032 trial, showing improved event-free survival. • Eflornithine's safety profile includes manageable toxicities like hearing loss, with dose adjustments potentially mitigating adverse effects. • While some panel members expressed concerns about using an externally controlled trial, the overall consensus was that the benefits outweigh the risks.